ABOi renal transplantation was considered unwise in the past because of ABMR and early graft loss. The long stay, waiting for a compatible donor was the real potentiation toward ABOi-rTX especially after development in the pre-transplant management.
This systemic review and meta-analysis reviewed the registered data up to 2017, looking for the outcome of ABOi-rTX in comparison to ABOc-rTX
Study findings:
· Study findings showed that ABOi-TX had an inferior outcome regarding: patient and graft survival, infectious and non-infectious complications, and graft rejection episodes.
· The refinement in the desensitisation protocols and the implementation of less intensive immunosuppressive regimens improved patient and graft survival.
· Inclusion of rituximab therapy decreased the risk of ABMR 5 years after transplantation.
· Rituximab seems not to be effcient in reducing the concentration of preformed anti- HLA antibodies or preventing the development of de-novo anti-HLA antibodies, both well known and strong risk factors for chronic ABMR and poor graft outcomes.
· The risk for polyoma nephropathy was not lower after ABOi-rTx than after ABOc-rTx in patients who received non-rituximab-based desensitisation protocols. This higher mortality could be a result of side-effects due to an over- suppressed immune system following desensitisation with emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus).
· Polyoma nephropathy is probably another reason for the lower graft survival after ABOi-rTx,
· Higher rates of bleeding events are reported after ABOi- rTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis or high- volume plasma exchange, or both.
level of evidence:
systemic review and meta-analysis; level of evidence I a
The week points in the study:
· The study’s endpoints did not address all consented core outcome domains for studies of kidney transplantation.
· The study didn’t address other comorbidities like cardiovascular diseases, DM and stability of graft function.
· Different immunosuppressive protocols were used between studies.
· The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years.
· An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
· Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
· Diferences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
· The analyses didn’t cover ABOc-rTx from deceased donors.
The strong points in the study:
· Systemic review and meta-analysis.
· 40 studies out of 1216 studies were included in the systemic review.
· The study group was fair enough to conclude that the outcome data for ABOi-rTx within the first 3 years after transplantation are worse than for ABOc-rTx, but the results should not be considered conclusive.
Alyaa Ali
2 years ago
A systematic review and meta-analysis was done to investigate differences in outcome after ABOi-rTX and ABOc-rTX.
This meta-analysis included 40 studies . All studies were published between Jan 27, 1998, and Sept 1, 2017, and included 65063 patients in total. The number of paediatric and adult recipients of ABOi-rTx ranged between ten and 1878 for the included studies, and the number of ABOcrTx recipients ranged between 21 and 26504.
Compared with ABOc-rTX, ABOi-rTx was associated with a higher risk of 1-year mortality , 3-year mortality , 5-year mortality , but not of 8-years or more mortality.This higher mortality could be a result of side-effects due to an oversuppressed immune system following desensitisation with emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus)
At 1 year, death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx. At 3 years, death-censored and death-uncensored graft survival was lower after ABOi-rTx than after ABOc-rTx. At 5 years. Death-uncensored , but not death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx. At 8 years or more . Death-censored , and death-uncensored graft survival were not lower after ABOi-rTx than after ABOc-rTx.
The proportion of patients with sepsis was higher after ABOi-rTx than after ABOc-rTx . No statistically significant difference was observed in the risk of urinary tract infections , cytomegalovirus infection, BK polyomavirus infection , and P jirovecii pneumonia .
Higher rates of bleeding events are reported after ABOi-rTx than after ABOc-rTX, .probably due to changes of the coagulation system following plasmapheresis or high volume plasma exchange, or both. Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles are more common after ABOi-rTx.
No significant difference between treatment groups was observed in overall , borderline , or T-cell mediated rejections . By contrast, the proportion of patients with ABMR was higher after ABOirTx than after ABOc-rTx .
With the introduction of a desensitisation strategy that includes rituximab (instead of splenectomy), excess mortality with ABOi-rTx was only seen within the first 3 years, and death-censored graft survival became similar to that of ABOc-rTx within the first year.
level of evidence provided by this article?
systematic review and meta-analysis : level of evidence 1
The week points of this study
The endpoints did not address all consented core outcome domains for studies of kidney transplantation. Only some items were encompassed in the primary studies and could be analysed. Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years.
An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
The strong points of this study
the study level 1 evidence systematic review and meta-analysis
with large numbers of studies included large number of patients with different countries and ethnicity.
Last edited 2 years ago by Alyaa Ali
MICHAEL Farag
2 years ago
This systematic review and meta-analysis is based on transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia. The advent of ABOi-rTx provides novel options for patients in need of a transplant organ with a living donor. For most countries, a paired donation programme to circumvent the immunological challenge of ABO incompatibility is precluded by law. Thus, ABOi-rTx remains the only option. This meta-analysis clearly shows that even with the most advanced desensitisation protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX. This higher mortality could be a result of side-effects due to an oversuppressed immune system following desensitization with emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus)
What are the week and strong points of this study?
– endpoints did not address all consented core outcome domains for studies of kidney transplantation. Only some items of the core outcome sets were encompassed in the primary studies and could be analysed. – Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient reported outcomes, could not be addressed because studies included in the meta-analysis did not report them. – Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen. – The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years. – An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated. – Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors. – Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
• What is the level of evidence provided by this article? Level I
Balaji Kirushnan
3 years ago
Summary of the article:
This was a systematic review and meta analysis of a large number of observational studies published till Dec 31, 2017. It included different population groups like adults and pediatrics…The study was published in the LANCET in 2019…Outcome data was reported for ABOi renal transplants when compared to ABOc transplants…small case reports and editorials were excluded from inclusion in the meta analysis. It included more than 40 studies from Us, Europe, Asia and Australia….The primary end points were all cause mortality and graft survival at 1,3,5 and >8 years after transplantation….
The meta analysis concluded that ABO-i has a higher mortality at 1-, 3- & 5-year compared to ABO-c transplantation. The high mortality was related to the intense immunosuppression from desensitization treatments.
Graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants.
At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants.
The risk of infections & surgical complications was higher in ABO-i vs ABO-c renal transplants.
TCMR rates was not different between both groups
However the rate Antibody mediated rejection was higher in ABO-i vs ABO-c transplants.
Discussion:
The analysis of the Lancet Metanalysis demonstrates a clear benefit of ABOc renal transplants as compared to ABOi renal transplants at 1,3,5 years….Graft survival and Patient survival improved and equaled ABOc transplants only after 8 years of ABOi renal transplants. This is due to the current desensitization strategies used which is associated with higher incidence of bacterial sepsis and viral infections (Polyoma and CMV)…Various studies have addressed the issue for tailored desensitization to reduced the risk of over immunosuppression….Surgical complications like wound infection, bleeding and lymphocele were more common after ABOi renal transplants. …The use of IA columns have been associated with thrombocytopenia and increased risk of post operative bleeding….The study also emphasizes the need of other studies using rituximab lower dose protocols like 200mg instead of 375mg/m2…Few studies even did transplants even without rituximab…The meta analysis also used the risk of increased risk of BK virus nephropathy which can cause graft loss…..The reason to use rituximab was a reduced incidence of ABMR after transplant….Although this was seen across many observational studies, the side effects of over immunosuppression namely infections and development of PTLD have been reported….
The limitations of the metanalysis was randomized trails were not included…The analysis compared studies using different protocols which used different cut off of Anti A/b titre and different isoagglutinin measurement strategies….Other parameters like cardiovascular diseases, graft outcome were not analyzed…
The evidence of the article is Level 1
Mohamed Essmat
3 years ago
Systemic review -meta-analysis of level 1 evidence the ABOi transplantation became an accepted option to overcome the shortage of both deceased & live donor pools .
It is a systemic review that Included 40 studies of ABOi transplantation with AbOc patients as control group from USA, Europe, Asia & Australia, with follow-up for more than 1 year.
Primary outcome: graft survival and all cause mortality at 1,3,5 and 8 years .
Secondary outcome: infections , surgical complications and graft rejection.
Results:
The benefit of ABOc Tx is more than ABOi Tx in the first 5 years post transplant.
patients mortality was higher in ABOi Tx in the first 5 years .
ABOi-T associated with higher rate of bleeding as well as more post op surgical complications .
serious infection was associated with use of rituximab( high dose) during desensitization or during peri-transplant conditioning.
High rate of mortality among ABOi-T patients which can be overcome by using Rituximab As risk of ABMR in patients with rituximab was reduced & it comparable to ABOc-T 5 years after transplantation.
Wee Leng Gan
3 years ago
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis.
This is a systematic review and meta-analysis of observational studies with level 1 evidence.
The objective of this systemic review is to study all-cause mortality and graft survival among the ABO incompatible kidney recipients at 1, 3, 5, and more than 8 years after transplantation. This meta-analysis included observational studies published up until Dec 31, 2017, that reported outcome data (at least 1 year of follow-up) after ABO incompatible kidney transplant and ABO-compatible as control group. However, case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABO compatible kidney transplant were excluded. This meta analysis revealed that ABO incompatible kidney transplant was associated with significantly higher 1-year mortality (odds ratio [OR] 2.17 [95% CI 1.63–2.90], p<0.0001; I²=37%), 3 years (OR 1.89 [1.46–2.45], p<0.0001; I²=29%), and 5 years (OR 1.47 [1.08–2.00], p=0.010; I²=68%) following transplantation. Death-censored graft survival was lower with ABO incompatible kidney transplant than the control group at 1 year (OR 2.52 [1.80–3.54], p<0.0001; I²=61%) and 3 years (OR 1.59 [1.15–2.18], p=0.0040; I²=58%) only. Graft losses were equivalent to that of ABO compatible transplant recipients after 5 years and patient survival after 8 years. There is clear advantages for ABO compatible renal transplant compare to ABO incompatible renal transplant in the first 5 years following transplantation. Higher mortality were observe among ABO incompatible group due to risks of over immune suppression by intensified desensitization protocol and complicated with opportunistic infections. Besides, bleeding risks was higher among ABO incompatible group due to unselective plasmapheresis and immunoadsorption. In the first 5 years post ABO incompatible transplantation, risk of graft failure was high due to antibody mediated rejection and polyoma nephropathy especially HLA incompatible kidney recipients. However, long term data after 8 years revealed that no difference between both groups among the survivors. To overcome the negative outcome in ABO incompatible kidney transplant we need to refine and individualising the desensitising protocol and carefully select the maintenance immunosuppressive regimen for ABO incompatible kidney recipients. Limitations of this meta analysis include not assessing some of the important risk factors such as diabetes mellitus, cardiovascular disease and stability of graft function. Besides, variation of immunosuppressive protocol were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen. Furthermore, most of the observational studies were shorter than 5 years. On the other hand, this meta analysis involved large number of patients with high level of evidence in field of ABO incompatible renal transplant. In my opinion, we should carefully select potential candidate for ABO incompatible kidney transplants. We should explain in details regarding the risks and the long journey of immune desensitisation and immunosuppressant protocol. Early detection of complications and prompts action are crucial. Paired kidney exchange may serve as alternative for the deficiency of ABO incompatible kidney transplant. However, ethical issues and administrative barriers exist need to be taken into consideration.
Ramy Elshahat
3 years ago
summery
meta-analysis of 40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia>>>
The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-RTX in the first 5 years following organ implantation. Only long-term data after 8 years indicate the equal performance of the procedures for survivors Graft losses were equivalent to that of ABOc-RTX after 5 years and patient survival after 8 years but the risks of post-operative complications, infections, and rejection were higher in ABOi-RTX so ABOi-RTX transplantations are still an option for ESRD patients but still inferior to ABOc. The alternate option to circumvent ABOi-RTX would be paired kidney exchange, which has been established in numerous centers
What is the level of evidence provided by this article?this study is a meta-analysis of observational studies >>> level of evidence 2a
strong points of this study?? · very large number of patients · different races were included from different countries
The limitations?? o endpoints did not address all consented core outcome domains for studies of kidney transplantation. o Only some items of the core outcome sets were encompassed in the primary studies and could be analyzed. Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient-reported outcomes, could not be addressed because studies included in the meta-analysis did not report them. o Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitization regimen. Therefore, the effectiveness of the principal isoagglutinin removal technique, starting isoagglutinin thresholds, or the exposure to a specific combination of immunosuppressive drugs could not be assessed. o The observational periods were shorter than 5 years in most studies and therefore fewer data were available for the analyses of clinical outcomes after 5 years. o duplication for the same patient cohorts could not be ruled out. o An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
also o the results should not be considered conclusive due to the heterogeneity in the included study cohorts, with discordances in donor and recipient ages and immunological risk factors. Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies. o the study did not cover ABOc-RTX from deceased donors or HLA-incompatible renal transplantation. A multipronged comparison of all four modalities (ABOi-RTX vs living ABOc-RTX vs deceased donor ABOc-RTX vs continued dialysis) in the context of a multicentre study or a network meta-analysis could help to further clarify the raised safety and efficacy issues.
Future questions need to be answered
· Further improvements in the immunological tests to combat blood group incompatibility-related complications can be achieved.
· A reduction in the dose of the immunosuppressive drugs applied could be beneficial
· how to use Pre-emptive antibiotics and virus-static therapy are also options to consider. · how to monitor the coagulation system to decrease the risk of bleeding following plasmapheresis and immunoadsorption.
Batool Butt
3 years ago
Summarise this article
The ABOi transplantation became an accepted option to overcome this shortage of both deceased & live donor pools. This systematic review and meta-analysis of observational studies assess the effect of ABOi transplantation on graft survival, patient survival at 1, 3, 5, and more than 8 years after transplantation ,infectious & non -infectious compared to ABOc transplantation. Results and conclusion
ABOi when compared to ABO-compatible transplantation is associated with the following :
1-Higher risk of ABMR and mortality but not TCMR
2-Lower graft survival in the first 3 years post transplantation, but long term graft survival at 08 years is comparable to ABO compatible transplantation
4-Lower Death-censored graft survival at 1 and 3 years but not at 5 years post transplantation
5-Bleeding is the most common surgical complications related to ABO I transplantation due to removal of clotting factors by plasmapharesis.
6-There is an increase in the risk of infections and sepsis in ABOi when compared to compatible transplantation including pneumonia, UTI, wound infection, PCP, CMV and BK virus, which may be attributed to the use of rituximab.
7-Surgical revisions and lymphoceles are more frequently seen in ABOi transplantation due to unclear reason.
In short,efforts toward paired kidney donation programs should be maximized and combined with desensitization protocols to get more favourable outcomes.
What is the level of evidence provided by this article?
It is a systematic review and meta-analysis, level of evidence I What are the weak and strong points of this study?
The strength of this study is its meta-analysis nature with level I of evidence and including very large pool of patients from different populations . ABOi-rTX may better than remaining on dialysis Weakness arise from the lack of addressing other endpoints- no reports from the included studies about comorbid conditions like DM, cardiovascular disease, stability of graft function, different protocols used so increasing bias when interpreting the results, moreover most of the studies are of short term duration < 5 years, and clinical outcomes after 5 years cannot be analyzed. The exact time of complications( infections,surgical, and immunological) were not reported
Jamila Elamouri
3 years ago
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis
Kidney transplantation is the best renal replacement therapy, however, most patients remain long on a waiting list because of the scarcity of organs from deceased donors. ABO-incompatible kidney transplantation has been driven to overcome the problem of organ shortage by expanding the living donor pool. Pre-transplant desensitization strategies have been developed to overcome the isoagglutinin immunological barrier. This is done by plasmapheresis or immunoadsorption and the depletion of antibody-producing cells with rituximab. Many studies revealed no differences between ABO-incompatible transplantation and ABO-compatible transplantation, others; show conflicting results. Therefore, ABOi renal transplantation is still not universally adopted by all transplant centres.
Method:
This systemic review and meta-analysis were done according to the PROSPERO protocol. The authors followed the recommendations by the Cochrane Collaboration, the PRISMA statement, and the GRADE guidelines.
Paediatric and adult recipients of ABOi renal transplant, if an ABO-compatible control group was included and if data of outcomes of at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria were case reports, editorials, reviews, and letters, animal studies, meeting papers, studies with extractable data, non-renal solid organ transplant studies, and bone-marrow transplant studies. Also, non-English articles. All full texts of all trials that fulfilled the eligibility criteria were investigated. Result and discussion:
The studies reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation. While long-term data after 8 years indicate the equal performance of both procedures for survivors. By the use of desensitization protocol with rituximab excess mortality with ABOi-rTx was only seen within the first 3 years, and death censored graft survival became similar to that of ABOc-rTx within the first year.
Paired kidney donation is one of the options to overcome the immunological barriers, although it is precluded by many countries by the law. Thus, ABOi-rTx remains the only option.
The study reveals that patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTx. This contributed to the over-suppressed immune system following desensitization causing high rate of infection such as CMV and polyoma nephropathy was higher in ABOi-rTx.
ABOi-rTx carries a higher incidence of bleeding, as a result of changes in the coagulation system. Lymphoceles are more common after ABOi-rTx.
The graft survival with ABOi-rTx was lower which is in line with a high risk of ABMR.
Rituximab-based desensitization protocols were clearly reducing the risk of humoral rejection, and the risk of ABMR in ABOi-rTx group was similar to that in the ABOc-rTx group 5 years after transplantation if rituximab was initially used.
Limitations: weak points
1- Not all consented core outcome domains did not address.
2- Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient-reported outcomes, could not be addressed.
3- Different immunosuppressive protocols and isoagglutinin thresholds were used between studies, so it is impossible to assess the effect of a specific induction and desensitization regimen.
4- The observational periods were short.
5- Heterogeneity in the included study was substantial, with discordances in donor and recipient ages and immunological risk factors.
6- Accurate report of the time after transplantation at which complications occurred was not stated.
7- Different patients characteristics.
strong points:
1- high level of evidence
2- a large number of patients
3- many countries
level of evidence:
Level 1- a meta-analysis
Nasrin Esfandiar
3 years ago
This article is a systematic review and meta-analysis of only observational studies up to 2017. Inclusion: All recipients of ABOi-KT were assessed if there was a control group of ABO compatible and at least one-year follow-up or more. Forty studies used for analysis among 1264 references that were published up to 2017. Cochrane, Embase, MEDLINE and PubMed were searched. Primary outcome were graft survival and mortality at 1, 3, 5 and more than 8 after TX. Secondary outcomes were infections and non-infections complications and rejections. Totally 40 studies were included for adult and pediatric recipients. ABOi-TX was associated with higher risk of 1,3 and 5 years mortality but not for 8-years or more mortality. At one and three years, death-censored graft survival was lower in ABOi-TX group comparing ABOC-TX group. More patients with sepsis, and surgical revision were included in ABOi-TX group. In addition, ABMR was more common in patients in ABOi-TX group. So, even with advanced protocols, patient mortality is higher in ABOi-TX due to over-immunosuppression or infections, especially if rituximab is used, although it decreased rate of ABMX.
The level of evidence provided by this article is 1.
Weak points: Not including outcomes such as cardiovascular diseases, stability of graft, diabetes, different desensitization and immunosuppression protocols. Not including isoagglutinin thresholds or removal technique, less data for outcome after 5 years.
Duplication bias can’t be ruled out. No RCTs
Strong points:
No bias regarding the outcome was seen. The level of evidence of this article is high and included large number of patients.
mohamed hefzy
3 years ago
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis
Summarise this article
summary
This is a systematic review & meta-analysis of a large number of observational studies published up until Dec 31, 2017. It included a diversity of population of both adults & pediatrics.
The primary endpoints were all-cause mortality & graft survival at 1, 3, 5, & >8 years after transplantation.
ABO-i has a higher mortality at 1-, 3- & 5-year compared to ABO-c transplantation. The high mortality was related to the intense immunosuppression from desensitization treatments.
Graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants.
At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants.
The risk of infections & surgical complications was higher in ABO-i vs ABO-c
TCMR rates was not different between both groups, however the rate AMR was higher in ABO-i vs ABO-c transplants.
results
Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality 3 years and 5 years following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year and 3 years only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
discussion
This systematic review and meta-analysis is based on transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies involving more than 65000 patients . The analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation. Only long-term data after 8 years indicate equal performance of the procedures for survivors
even with the most advanced desensitisation protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX.
What is the level of evidence provided by this article?
Type of study meta-analysis systemic review
Level 1
What are the weak and strong points of this study?
Strong points
Meta-analysis with high level of evidence and involving large number of patients with long term follow up from different countries.
Weak Points
different immunesuppressive protocol.
other domain like CVS,DM,graft outcome not addressed.
observational studies
observational period shorter than 5yrs in many studies.
Summarise this article :
Introduction :
ABO-incompatible renal transplantation (ABOi-KT) is considered other option for patients on waiting list for long periods with no comptatible donors
This systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that compare data of 2 groups of ABOI-KT and ABOC-KT including 40 studies including 49 patient groups were identified.
65063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx.
Results :
At 1 , 3 and 5 year graft survival was lower after ABOi-KT than after ABOc-KT.
But at 8 years. Death-uncensored and death-censored graft survival weren’t lower after ABOi-KTthan after ABOc-KT.
-Sepsis was higher after ABOi-KTthan after ABOc-KT
-Surgical revision for hematoma, bleeding, and lymphocele was more in ABOI-KT than ABOc-KT.
-ABMR was higher in ABOi-KT than in ABOc-KT but No significant difference between ABOi-KT and ABOc-KT according to T-cell mediated rejection.
Using Rituximab in desensitization in ABO i making graft survival equal with ABO c KT
The risk of sepsis and cytomegalovirus infections was significantly higher in ABOi-KT patients that didn’t receive rituximab on desensitization protocol than in ABOc-KT.
No significant differences between ABOi-KT and ABOc-KT were found according to P jirovecii pneumonia and urinary tract infections, with any of the different desensitization protocols.
the risk of ABMR was significantly lower in ABOi-KT if Rituximab was used in desensitization protocols.
Discussion:
ABOc-KT was more beneficial with fewer hazards than ABOi-KT in the first 5 years of renal transplantation however they were equal on follow-up after 8 years.
The introduction of rituximab in desensitization protocols improves death-censored graft survival of ABOi-KT to be equal to ABOc-KT within the first year.
Patient mortality is higher in the first 5 years after ABOi-KT than after ABOc-KT.
What is the level of evidence provided by this article?
level 1 ( meta-analysis )
Strong points :
– Large numbers of the study sample
• Meta-analysis study with a high level of evidence
Weak Points :
· Cardiovascular risks and stability of graft functions were not studied.
· No specific protocol of desensitization or immunosuppression due to many different protocols were included in the studies used in meta-analysis
· Observational period was mostly 5 years with less information of outcome after 5 years.
· Accurate time of infectious and non-infection complications weren’t reported accurately.
· Differences in patients characteristics that may affect the outcome of KT, such as frailty status, duration of dialysis before transplantation, cardiovascular disease, and primary diseases, were not assessed in most of the studies
Mohamed Ghanem
3 years ago
Summarise this article : Introduction :
ABO-incompatible renal transplantation (ABOi-KT) is now indicated as another option for patients on the long waiting lists with no available compatible donor.
This systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that compare data of 2 groups of ABOI-KT and ABOC-KT including 40 studies including 49 patient groups were identified.
65063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx. Results : At 1-year graft survival was lower after ABOi-KTthan after ABOc-KT.
At 3 years graft survival was lower after ABOi-KTthan after ABOc-KT.
at 5 years. Death-uncensored,but not death-censored graft survival was lower after ABOi-KTthan after ABOc-KT
At 8 years. Death-uncensored and death-censored graft survival weren’t lower after ABOi-KTthan after ABOc-KT.
Sepsis was higher after ABOi-KTthan after ABOc-KT No statistically significant difference was observed in the risk of urinary tract infections, CMV.BK and P jirovecii pneumonia.
Surgical revision for hematoma, bleeding, and lymphocele was more in ABOI-KT than ABOc-KT.
ABMR was higher in ABOi-KT than in ABOc-KT.
No significant difference between ABOi-KT and ABOc-KT according to T-cell mediated rejection.
Death-censored graft survival at 1 year and 3years were equal in the ABOi-KT and the ABOc-KT if the desensitization program included Rituximab however was higher in ABOi-KT if Rituximab wasn’t used.
Death-censored graft survival at 5 years was equal in the ABOi-KT and the ABOc-KT if the desensitization program included Rituximab or not.
The risk of sepsis and cytomegalovirus infections was significantly higher in ABOi-KT patients that didn’t receive rituximab on desensitization protocol than in ABOc-KT.
No significantdifferences between ABOi-KT and ABOc-KT were found according toP jirovecii pneumonia and urinary tract infections, with any of the different desensitization protocols. the risk of ABMR was significantly lower in ABOi-KT if Rituximab was used in desensitization protocols. Discussion: ABOc-KT was more beneficial with fewer hazards than ABOi-KT in the first 5 years of renal transplantation however they were equal on follow-up after 8 years. The introduction of rituximab in desensitization protocols improves death-censored graft survival of ABOi-KT to be equal to ABOc-KT within the first year. Patient mortality is higher in the first 5 years after ABOi-KT than after ABOc-KT.
What is the level of evidence provided by this article?
level 1 ( meta-analysis ) Strong points :
· Meta-analysis study with a high level of evidence
· Large numbers of the study sample
· No publication bias was detected
· Trial sequential analysis confirmed that the meta-analysis was conclusive regarding the anticipated intervention leading to the required information size for mortality at 1 year, 5 years
· Many points were studied graft survival, patient mortality, complications of renal transplantation, and some desensitization protocols and their effects.
Weak Points :
· Only some items could be analyzed but others like cardiovascular risks and stability of graft functions were not studied in studies included in the meta-analysis
· Difficult study of specific desensitization or immunosuppression protocols due to many different protocols were included in the studies used in meta-analysis
· Observational period was mostly 5 years with less information of outcome after 5 years.
· The possibility of patient cohorts included in national registry analyses as well as smaller single-center studies could not be ruled out.
· Accurate time of infectious and non-infection complications weren’t reported accurately.
· Heterogeneity in the included studies (Ages of both donors and recipients–immunological risks
· Differences in patients characteristics that may affect the outcome of KT, such as frailty status, duration of dialysis before transplantation, cardiovascular disease, and primary diseases, were not assessed in most of the studies
· Analyses do not cover ABOc-KTfrom deceased donors with the need for studying all four modalities (ABOi-KT vs living ABOc-KT vs deceased donor ABOc-KT vs continued dialysis)
nawaf yehia
3 years ago
Kidney transplantation is the renal replacement therapy option with the greatest benefit for patients with end-stage renal disease . For this reason , many strategies developed to overcome organ shortage including transplantation against ABO incompatibility barrier. In order to compare the outcomes between ABOi & ABOc Kidney Transplantation , a systematic review and meta-analysis of observational studies published up until Dec 31, 2017 , was conducted to compare ABOi-rTx in terms of graft survival, patient survival, and infectious and non-infectious complications to those of ABOc-rTx, and whether the effects were similar after taking different desensitisation strategies into consideration, such as the incorporation of rituximab based protocols. Data analysis Predefined primary outcomes were graft survival and all-cause mortality at 1, 3, 5, and more than 8 years . after transplantation. Secondary outcomes were infectious and non-infectious complications, and graft rejections. (Infectious complications included sepsis, urinary tract infections, cytomegalovirus infection, BK polyomavirus infection, and Pneumocystis jirovecii pneumonia. Non-infectious complications included surgical revisions, haematomas, lymphocoeles, and ureteral complications) Results After excluding incompete reports , 40 studies were included in the meta- analysis. . as compared to ABOc KT : 1) MORTALITY. ABOi- rTx was associated with with a higher risk of 1-year mortality , 3-year mortality , 5-year mortality ), but not of 8-years or more mortality . However, subgroup analyses shows that 5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group 2 ) GRAFT SURVIVAL .At 1 year & 3 years :, death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx, as was death-uncensored graft survival . Althogh , Death-censored graft survival at 1 year was equal in the ABOi-rTx and the ABOc-rTx group, if the inital desensitisation protocol included rituximab . ( so it was worse in the non rtuximab group) 3) graft survival data after 5 years did not show significant differences between treatment groups when groups were analysed according to whether or not they received a rituximab desensitisation protocol 4) INFECTIONS. The risk of sepsis and cytomegalovirus infections after ABOi-rTx was significantly higher than after ABOc-rTx in patients who received non-rituximab-based desensitisation protocols, but no difference was seen between treatment groups in those who received rituximab-based desensitisation protocols . A higher risk for polyoma nephropathy was observed after ABOi-rTx than after ABOc-rTx in patients who received rituximab-based desensitisation Regarding P jirovecii pneumonia and urinary tract infections, no significant differences between ABOi-rTx and ABOc-rTx were found with any of the initial desensitisation protocols Additionally, the risk of serious infections and infectionrelated mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant conditioning regimens 5)REJECTION.ABOi-rTx (rituximab or non rituximab group ) was not associated with significantly more overall rejections, borderline rejections, or T-cell mediated transplant rejections than was ABOc-rTx . There was a trend for a higher risk of ABMR after AB0i-rTx than after AB0c-rTx with both desensitisation protocols .Nevertheless, the risk of ABMR was significantly lower if an initial rituximab-based desensitisation protocol was used. 6)SURGICAL COMPLICATIONS . Higher rates of bleeding events are reported after ABOirTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis . Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles are more common after ABOi-rTx.
LEVEL OF EVIDENCE : level 1 ( meta-analysis )
Weak points in this study :
1) The endpoints did not address all consented core outcome domains for studies of kidney transplantation.
2) Other important domains, such as cardiovascular disease, stability of graft function or diabetes could not be addressed because studies included in the meta-analysis did not report them.
3)Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
4) The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years.
Strong points :
Being a meta-analysis study with high level of evidence and involving a large overall No. of patients .
Wael Jebur
3 years ago
This paper reviewed observational studies performed up to 2017,to compare ABOi with ABOc renal transplant outcome in term of patient and allograft survival. elaborating on infectious and non infectious complications reporting on all cause mortality and allograft survival.
features of this study:
1] 40 studies .
2] 65000 patients, with ABOi and ABOc transplantation.
3] All studies were systematically reviewed and were only observational conducted until the year 2017.
4 ]End points were all -cause mortality and and graft survival at 1,3, 5 and 8 years after transplantation.
Results:
1] it clearly showed statically significant benefit of ABOc over ABOi transplantation in term of all cause mortality and Allograft survival in the 1,3 and 5 years post transplant and they are equal after wards.
2]The high mortality rate in the first 5 years in the ABOi transplantation is obviously related to over immunosuppression and desensitization protocol.
3]The over immunosuppression predisposed to bacterial infection ,like sepsis and viral infection as CMV and BKV Nephropathy.
3] High rate of bleeding events in ABOi transplantation due to PP and IA.
4] Surgical complication, lymphocele and hematoma, surgical revision and wound infection.
5]Death censored graft survival was less in line with higher AMR in ABOi.
6]Polyoma nephropathy was more common in ABOi ,which might explain the lower graft survival in this group.
7] Early mortality post ABOi transplantation was shown to be less when the immunosuppression protocol modified to avoid Rituximab or to reduce the dose of MMF.
8]There is improvement in graft survival after 3 years post ABOi transplantation.
9] Risk of AMR is less 5 years after ABOi transplantation.
limitations and drawbacks
1]The general limitations related to meta analysis study.
2]Other important end points domains like cardiovascular disease, stability of allograft function ,DM, and meaningful patients reported outcomes were not addressed in this study.
3]The observational period was less than 5 years in most studies, therefore no information was available to assess long term outcome of study.
4]duplication of patients cohort.
5] Heterogeneity in the included study cohorts was substantial.
6]differences in patients characteristics ,that might affect the transplantation outcome were not reported.
points of strength in this study:
1] Involvement of large no. of patients.
2]Different countries.
3] Long term follow up period.
level of evidence is 1 as its a meta-analysis study.
Zahid Nabi
3 years ago
Summary
It’s a systematic review and meta-analysis of observational studies published up until Dec 31, 2017 to investigate di!erences in outcome after ABOi-rTX and ABOc-rTX.
Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
A total of 1264 studies were screened and 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx. Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year , 3 years and 5 years mortality following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
Level of evidence
1.
What are the week and strong points of this study?
This study did not address all the core outcomes as endpoint supposed to be for studies of kidney transplantation e.g cardiovascular disease, and stability of graft function.
Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
outcome analysis after 5 yrs was not possible as Less data were available for the analyses of clinical outcomes after 5 years.
Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
. Differences in patients’ characteristics that might have an effect on transplantation outcomes was not reported in most of studies.
Strength of study
It was the most extensive synthesis of available evidence assessing clinical outcomes of ABOi-rTx in comparison with ABOc-rTx.
Shereen Yousef
3 years ago
Summarise this article
*This systematic review and meta-analysis
Level of evidence is 1.
*ABOI-KT was considered a contraindication indication in the past but it started to be widely accepted in many centres due to shortage of donors and long waiting time on dialysis.
Recent advances in immunosuppssion and desensitization protocols allowed more ABOI-RTX.
*This is a systemic review of transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies including 49 patient groups and more than 65000 patients of which 7098 had ABOi-Tx.
aiming to investigate differences in outcome.
*Results
-There was a clear benefit of ABOc-Tx over ABOi-Tx in 5 years after implantation.
– longer follow up for 8 years both groups showed the same survival rates .
– Inclusion of rituximab therapy decreased the risk of ABMR within 5 years after transplantation also
desensitisation with rituximab improved survival and death-censored graft survival after 1 year to be equal to recipients of ABOc-rTx
But still the risk of ABMR
higher after ABOi-rTx than after ABOc-rTX.
-patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX.
infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus) was the main cause of death
– other common complications includes hemorrhage, Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles.
-avoidance of aggressive initial immunosuppressive protocols and individualising the immunosuppressive therapy reduced the higher early mortality.
*What are the weak and strong points of this study?
•Strength points
-Systemic review with high level of evidence
-Large number of studies were reviewed with large number of patients.
-showed good results of adding rituximab to induction and good resullts avoiding aggressive immunosuppression.
•Limitations:
-endpoints did not address all consented core outcome domains for studies of kidney transplantation.
– didn’t addresse other complications as CVD, stability of graft function, diabetes, or meaningful patient-reported outcomes.
-Different immunosuppressive protocols were used between studies.
-The observational periods were shorter than 5 years in most studies and less data were available for the analyses of clinical outcomes after 5 years.
– inclusion criteria of patients in the studies were not uniform .
-didn’t cover ABOc-rTx from deceased donors.
Mohammed Sobair
3 years ago
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis:
Aim:
To investigate differences in outcome after ABOi-rTX and ABOc-rTX.
Introduction:
Removal of is isoagglutinins by plasmapheresis or Immunoadsorption and the depletion
of antibody producing cells with rituximab, have enabled ABO incompatible renal
transplantation (ABOi-rTx).
Methods:
A systematic review and meta-analysis of observational studies.
Search strategy and selection criteria this systematic review and meta-analysis.
Data analysis Predefined primary outcomes were graft survival and all-cause mortality at
1, 3, 5, and more than 8 years.
Secondary outcomes were infectious and non-infectious complications, and graft
rejections. Infectious complication.
Result:
Mortality risk:
Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year
mortality, 3 years and 5years posttransplant. Death-censored graft survival was lower
with ABOi-rTx than with ABOc-rTx at 1 year and 3yearsbut not at 8years.
Rituximab-based versus no rituximab-based desensitation protocols revealed higher 1-
year and 3-year mortality after ABOi-rTx than after ABOc-rTx regardless of the initial
desensitisation protocol.
5 years after transplantation, ABOi-rTx was not associated with significantly higher
mortality than was ABOc-rTx in the rituximab group, compared with the group without
rituximab.
Graft losses:
Were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
At 1 and 3 year, death-censored graft survival was lower after ABOi-rTx than after ABOc-
rTx , as was death-uncensored graft survival.
At 5years, Death-uncensored but not death-censored graft survival was lower after
ABOi-rTx than after ABOc-rTx.
At 8 years or more Death-censored and death-uncensored graft survival were not lower
after ABOi-rTx than after ABOc-rTx.
Infection risk:
Sepsis was higher after ABOi-rTx than after ABOc-rTx .
No statistically significant difference was observed in the risk of urinary tract infections,
cytomegalovirus infection, BK polyomavirus infection, and P jirovecii pneumonia.
Surgical complication risk:
A greater proportion of patients who had ABOi-rTx had surgical revision than those who
had ABOc-rTX (, bleeding or hematomas, and lymphoceles.
No significant difference in the proportion of patients with surgically treated
lymphoceles or ureteral complications, between patients who had ABOi-rTx and those
who had who had ABOc-rTx.
Rejection Risk:
No significant difference between treatment groups was observed in overall, borderline,
or T-cell mediated rejections.
By contrast, the proportion of patients with ABMR was higher after ABOi rTX than after
ABOc-rTx .
Discussion:
The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5
years following organ implantation.
Only long-term data after 8 years indicate equal performance of the procedures for
survivors.
Excess mortality with ABOi-rTx was only seen within the first 3 years, and death-
censored graft survival became similar to that of ABOc-rTx within the first year.
Refining the initial immunosuppressive protocols may reduce risk of infection, bleeding
and surgical complication.
What is the level of evidence provided by this article?
level of evidence 1.
What are the week and strong points of this study?
Weak points:
Not include all consented core outcome domains for studies of kidney transplantation.
Other important domains, such as cardiovascular disease, stability of graft function,
diabetes, or meaningful patient reported outcomes, could not be addressed.
Different immunosuppressive protocols were used between studies, making it impossible
to assess the effect of a specific induction and desensitisation regimen.
The observational periods were shorter than 5 years in most studies and therefore less
data were available for the analyses of clinical outcomes after 5 years.
Differences in patients’ characteristics.
Discordances in donor and recipient ages and immunological risk factors.
strong points :
metanalysis study .
Large number of patient.
High level of evidence.
Filipe prohaska Batista
3 years ago
The aim of the study;
was to investigate differences in outcome after ABOi-Tx and ABOc-Tx
The type of the study;
This systematic review and meta-analysis.
Population;
More than 65 000 patients originated from the USA, Europe, Asia, and Australia. 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-Tx.
Conclusions
Compared with ABOc-Tx, ABOi-Tx was associated with significantly higher 1-year mortality 3 years and 5 years following transplantation. Death-censored graft survival was lower with ABOi-Tx than with ABOc-Tx at 1 year and 3 years only. Graft losses were equivalent to that of ABOc-Tx after 5 years and patient survival after 8 years.
What is the level of evidence provided by this article?
Level 1
What are the weak and strong points of this study?
It is a meta-analysis and systematic review
High number of patients
Only some items of the core outcome sets were encompassed in the primary studies and could be analyzed.
Cardiovascular disease, stability of graft function, diabetes, or meaningful patient-reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
Different immunosuppressive protocols were used between studies.
The observational periods were shorter than 5 years in most studies and therefore fewer data were available for the analyses of clinical outcomes after 5 years.
An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
Mahmud Islam
3 years ago
This is a systematic review and meta-analysis with a level of evidence: I
This paper reviewed studies of ABO-incompatible transplantations till December 2017 compared to compatible ones. subgroup analyses included analysis of death censored and non-censored graft survival, sepsis, surgical revision, and rituximab based desensitization.
compare with ABO compatible Tx, ABOi-RT was associated with higher mortality in the first and 3rd years but equal after 8th year.
In 36 studies (59970 patients) death censored survival at one year was lower in the BO compatible group
Rituximab based desensitization protocols had higher mortality in the AO incompatible group both at 1st and 3rd years post-transplantation.. especially in the first 5 years the survival was higher with ABO compatibility compared to ABOi Tx. immune suppression and related infection seem to play a role in lower graft survival in ABOi transplants.
when we decide to transplant against ABO incompatibility, evaluation is beneficial to compare in relation ABO compatibility, deceased donor transplant, on and remaining on dialysis. Kidney paired donation should be considered as well
saja Mohammed
3 years ago
Summary:
Systematic review and meta-analysis assessing the best evidence available from the review of observational studies with > 1 year follow up. tin his review they compare the clinical outcome of ABOi TX with control group of ABOc KTX, about 1265references available for analysis and around 40 studies included from 1998- till 2017 by reviewing all the studies published in Cochrane(CENTRAL) , PubMed, embase , Midline
They exclude all case reports or editorial comments , letters, in adequate data or follow up < 1 year, animal studies, non-renal solid organ transplant, and non-English articles, they included 65000 of patients and about 7000 patients underwent ABOi KTX compared with ABOc living donor KTX as control group .the primary endpoint of 1,3 and 5 years graft survival , 8 Years mortality as secondary endpoint outcome.
Results:
ABOi-KTX associated with higher rate of infection in the first-year post TX, more surgical complication hematoma, bleeding lymphocele
The graft and patient survival were found lower in ABOI ktx in the first three years which can be explained by higher rate of infection and rejection, while 5 years clinical graft outcome were similar in the two group .and this review highlight the inferiority effect of ABOI ktx by all the points.
early higher mortality rate correlated to the intense immunosuppression including high dose rituximab with associated high risk of serious infections like CMV ,polyoma Viral infection , bacterial infection ,subgroup analysis from some studies reported better outcome and graft survival with desensitization protocols using low dose rituximab or rituximab free regimens
Death (censored and uncensored) graft survival was lower in ABOi KTX at one year,3 Years respectively , and its associated with higher ABMR rate while at 8 years the death censored and uncesord was not lower in ABOi tx compared to ABOcTX .
Using rituximab based desensitization protocol associated with lower rate of ABMR and more infections including sepsis , cmv ,BKV ,pjp
Over all the ABOi TX still associated with favorable outcome in highly sensitized patients compared to long waiting list on dialysis .according to the results from this review we should expand and encourage the use of paired kidney exchange program and limit the use of ABOI tx with tailored immunosuppression protocol for those whom failed to be included in PKD program .
Strength of the study
1-High level of evidence
2- using different statistical data analysis including sequential analysis to avoid bias
3-No publication bias correlated to graft survival as outcome.
Limitation of the study:
1- No RCT in this systematic review and meta-analysis
2- Not all outcome points are answered some domains that could affect the outcome other than infection and rejection not assessed like frailty score , cardiovascular disease, DM
3- heterogenicity of the patients characteristics might affect the outcome.
4- different immunosuppression and desensitization protocols
5- 5 years follow-up consider short observational period to address solid outcome .
Level of evidence : 1B( no single RCT , all from observational studies with heterogenicity in patients selections criteria and desensitization protocols )
Ahmed Abd El Razek
3 years ago
Introduction
The ABO blood group barrier has long been considered a contraindication to renal transplantation due to increased risk for humoral rejection and early graft loss. Now, this barrier is being crossed after the development of pretransplant desensitization strategies.
Methods Search strategy and selection criteria
Systematic review and meta-analysis
Results
Compared with ABOc-rTX, ABOi-rTx was associated with a higher risk of 1-year mortality, 3-year mortality, 5-year mortality, but not of 8-years or more mortality.
At 1 year, death-censored graft survival was lower after ABOi-rTx than after ABOc-rTX.
At 3 years, death-censored and death-uncensored graft survival was lower after ABOi-rTx than after ABOc-rTX.
The proportion of patients with sepsis was higher after ABOi-rTx than after ABOc-rTX.
No statistically significant difference was observed in the risk of urinary tract infections, cytomegalovirus infection, BK polyomavirus infection, and P jirovecii pneumonia.
A greater proportion of patients who had ABOi-rTx had surgical revision than those who had ABOc-rTX, bleeding or hematomas, and lymphocele.
The proportion of patients with ABMR was higher after ABOirTx than after ABOc-rTX.
Subgroup analyses of rituximab-based versus nonrituximab-based desensitization protocols revealed higher1-year and 3-year mortality after ABOi-rTx than after ABOc-rTX regardless of the initial desensitization protocol.
5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTX in the Rituximab group.
Death-censored graft survival at 1 year was equal in the ABOi-rTx and the ABOc-rTX group, if the initial desensitization protocol included rituximab.
Death-censored graft survival at 3 years was worse in the ABOi-rTx group given nonrituximab-based desensitization protocols than in the ABOc-rTX group.
The risk of sepsis and cytomegalovirus infections after ABOi-rTx was significantly higher than after ABOc-rTX in patients who received non-rituximab-based desensitization protocols.
A trend for higher risk for Polyoma nephropathy was observed after ABOi-rTx than after ABOc-rTX in patients who received rituximab-based desensitization protocols.
Regarding P jirovecii pneumonia and urinary tract infections, no significant differences between ABOi-rTx and ABOc-rTX were found with any of the initial desensitization protocols.
The risk of ABMR was significantly lower if an initial rituximab-based desensitization protocol was used.
level of evidence :1
weak points: No RCT (randomized controlled trial) was included in the review. No standard protocol was used in the different studies.
strong points: large size of population. high level of evidence.
Ahmed Omran
3 years ago
· A systematic review and meta-analysis of multiple observational studies from different populations of different age groups..
OUTCOMES following ABOI-KT
Mortality rate in the patients transplanted from ABOI donor is higher at 1, 3 and 5 years post-transplant in comparison with recipients with ABO compatible donor, and become similar at 8 years post transplantation; mostly attributed to side effects of aggressive immunosuppression like infections either bacterial and viral like BK virus, CMV, and coagulation disorders.
Incidence of AMR is higher in the patient with ABO incompatible compared to those with ABO compatible donor in spite of aggressive immunosuppression and use of rituximab.
level of evidence 1(Systematic review with meta analysis)
Strong points include involvement of large number of studies from different areas allow good scope of the patients and results.
Weak points include lacking of randomized clinical trials, some endpoints not mentioned in studies like cardiovascular risk, graft function stability, also use of different protocols of immunosuppression not allowing possible comparison to get real assessment , and follow up 5 years.
Reem Younis
3 years ago
.-The ABO blood group barrier has long been considered a contraindication to renal transplantation because of the increased risk for humoral rejection and early graft loss.
-Pretransplant desensitization strategies, such as the removal of isoagglutinins by plasmapheresis or immunoadsorption and the depletion of antibody-producing
cells with rituximab, have enabled ABOincompatible renal transplantation (ABOi-rTx).
-It systematic review and meta-analysis were done according to the PROSPERO protocol.
-It is based on transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies involving more than 65 000 patients originating from the USA, Europe, Asia, and Australia.
-The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation. Only long-term data after 8 years indicate the equal performance of the procedures for survivors.
-With the introduction of a desensitization strategy that includes rituximab excess mortality with ABOi-rTx was only seen within the first 3 years, and death-censored graft survival became similar to that of ABOc-rTx within the first year.
-The advent of ABOi-rTx provides novel options for patients in need of a transplanted organ with a living donor.
-Patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX. -This higher mortality could be a result of side effects due to an over suppressed
immune system following desensitization with the emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus).
-Higher rates of bleeding events are reported after ABOirTx than after ABOc-rTX, probably due to changes in the coagulation system following plasmapheresis or high volume plasma exchange, or both.
-Surgical revisions, with more postoperative wound infections, hematomas, and
lymphoceles are more common after ABOi-rTx.
-The risk of postoperative bleeding appears to be especially high if immunoadsorption is used.
-Cytomegalovirus prophylaxis protocols might explain the reduced proportion of patients with early cytomegalovirus infections at present, which obviates viral infections regardless of the cytomegalovirus risk status.
-The risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant conditioning regimens, or other immunosuppressive agents, in the course of the induction therapy.
-The higher early mortality after ABOi-rTx than after ABOc-rTX could be overcome by refining the initial immunosuppressive protocols and individualizing the immunosuppressive therapy.
– In smaller studies, selected patients receiving either a reduced dose of rituximab, no rituximab, or no plasmapheresis during the induction phase, or
lower doses of mycophenolate mofetil during the maintenance phase after ABOi-rTx showed exceptionally good outcomes with less infectious complications and
without increased incidence of acute rejection.
– The lower graft survival with ABOi-rTx was in line with a high risk of ABMR. Inclusion of rituximab therapy decreased the risk of ABMR 5 years after transplantation.
-Polyoma nephropathy was more common after ABOi-rTx than after ABOc-rTX in patients who received rituximab based desensitisation protocols.
-The risk of developing polyoma virus-associated nephropathy in patients who have undergone ABOi-rTx is even significantly higher than in recipients of HLA-incompatible kidney transplants.
-Patients undergoing ABOi-rTx are at higher immunological risk because of a
re-transplant condition, older age, unrelated donors, more HLA mismatches, or higher panel reactive and donorspecific antibody amounts, than are those undergoing ABOc-rTX.
– Rituximab isnot efficient in reducing the concentration of preformed DSA or preventing the development of de-novo DSA, both well known and strong risk factors for chronic ABMR and poor graft outcomes. Limitations of this study:
– Endpoints did not address all consented core outcome domains for studies of kidney transplantation. Only some items of the core outcome sets were encompassed in the primary studies and could be analyzed. Other
important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient-reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
-Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitization regimen.
-The observational periods were shorter than 5 years in most studies and
therefore fewer data were available for the analyses of clinical outcomes after 5 years.
–the strong point,it is meta analysis study involved large number of studies from different centres . Level of evidence: 1
CARLOS TADEU LEONIDIO
3 years ago
Summarise this article
INTRODUTION
The ABO blood group barrier has long been considered a contraindication to renal transplantation because of the increased risk for humoral rejection and early graft loss. However, pretransplant desensitisation strategies, such as the removal of isoagglutinins by plasmapheresis or immunoadsorption and the depletion of antibody producing cells with rituximab, have enabled ABO-incompatible renal transplantation (ABOi-rTx).
Although smaller studies evaluating patient and graft outcome after ABOi-rTx did not show any striking differences compared with living donor ABO-compatible renal transplantation (ABOc-rTx), larger registry data have showed conflicting results.
METHODS
This systematic review and meta-analysis was done according to the PROSPERO protocol, followed the recommendations by the Cochrane Collaboration, the PRISMA statement and the GRADE guidelines.
Were analysed studies of paediatric or adult recipients of ABOi-rTx, if an ABO-compatible control group was included and if outcome data for at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria were case reports, editorials, reviews and letters, animal studies, meeting papers, studies with unextractable data, non-renal solid organ transplant studies, and bone-marrow transplant studies. Non-English articles were excluded.
The following keywords were used, with the use of wildcard characters to account for variations in spelling and plurals: “ABO” OR “AB0” in combination with “incompatible” AND “renal” OR “kidney”; “ABOi” OR “AB0i” in combination with “renal” OR “kidney”. No other search restrictions were Applied.
DATA ANALYSIS
Data analysis Predefined primary outcomes were graft survival and all-cause mortality at 1, 3, 5, and more than 8 years after transplantation. Secondary outcomes were infectious and non-infectious complications, and graft rejections.
Because of the absence of randomised controlled studies identified in the search, the risk of bias was assessed by the use of the Newcastle-Ottawa Scale and included the following items: representativeness of the exposed population, appropriate election and comparison of the study groups, adequate ascertainment of exposure (preconditioning therapies), and accuracy of outcome assessment.
We calculated the summary estimates using Review Manager (RevMan, version 5.3) and trial sequential analysis program version 0.9 beta.15 We used a p value of 0∙033. Because cumulative meta-analyses are at risk of producing random errors due to sparse data and multiple testing of accumulating data, we used trial sequential analysis to assess this risk.
RESULTS
Compared with ABOc-rTX, ABOi-rTx was associated with a higher risk of 1-year mortality (D²=65%), 3-year mortality (D²=58%), 5-year mortality (D²=83%), but not of 8-years or more mortality (D²=0%).
The proportion of patients with sepsis was higher after ABOi-rTx than after ABOc-rTx (D²=0%). No statistically significant difference was observed in the risk of urinary tract infections (D²=48%), cytomegalovirus infection (D²=71%), BK polyomavirus infection (D²), and P jirovecii pneumonia (D²=0%).
A greater proportion of patients who had ABOi-rTx had surgical revision than those who had ABOc-rTX (D²=0%), bleeding or haematomas (D²=2%), and lymphocoeles (D²=82%). We found no significant difference in the proportion of patients with surgically treated lymphocoeles (D²=61%) or ureteral complications (D²=0%) between patients who had ABOi-rTx and those who had who had ABOc-rTx.
No significant difference between treatment groups was observed in overall (D²=69%), borderline (D²=74%), or T-cell mediated rejections (D²=0%). By contrast, the proportion of patients with ABMR was higher after ABOi-rTx than after ABOc-rTx (D²=51%).
Subgroup analyses of rituximab-based versus non-rituximab-based desensitation protocols revealed higher 1-year and 3-year mortality after ABOi-rTx than after ABOc-rTx regardless of the initial desensitisation protocol without rituximab. 5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group compared with the group without rituximab.
Death-censored graft survival at 1 year was equal in the ABOi-rTx and the ABOc-rTx group, if the inital desensitisation protocol included rituximab and was worse in the ABOi-rTx group than the ABOc-rTx if the inital desensitisation protocol did not include rituximab. Death-censored graft survival at 3 years was worse in the ABOi-rTx group given non-rituximab-based desensitisation protocols than in the ABOc-rTx group but was similar to the ABOc-rTX group in those who received rituximab-based desensitisation protocols. Studies reporting graft survival data after 5 years did not show significant differences between treatment groups when groups were analysed according to whether or not they received a rituximab desensitisation protocol.
The risk of sepsis and cytomegalovirus infections after ABOi-rTx was significantly higher than after ABOc-rTx in patients who received non-rituximab-based desensitisation protocols, but no difference was seen between treatment groups in those who received rituximab-based desensitisation protocols.
The risk for polyoma nephropathy was not lower after ABOi-rTx than after ABOc-rTx in patients who received non-rituximab-based desensitisation protocols, but there were only two studies reporting such data.
Regarding P jirovecii pneumonia and urinary tract infections, no significant differences between ABOi-rTx and ABOc-rTx were found with any of the initial desensitisation protocols.
In patients who received either rituximab or non-rituximab-based desensitisation protocols, ABOi-rTx was not associated with significantly more overall rejections, borderline rejections, or T-cell mediated transplant rejections than was ABOc-rTx. Nevertheless, the risk of ABMR was significantly lower if an initial rituximab-based desensitisation protocol was used.
DISCUSSION
The meta-analysis clearly shows that even with the most advanced desensitisation protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX. This higher mortality could be a result of side-effects due to an over-suppressed immune system following desensitisation with emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus).
Higher rates of bleeding events are reported after ABOi-rTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis or high volume plasma exchange, or both. Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles are more common after ABOi-rTx.
Cytomegalovirus prophylaxis protocols might explain the reduced proportion of patients with early cytomegalovirus infections at present, which obviates viral infections regardless of the cytomegalovirus risk status.
Additionally, the risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant conditioning regimens, or other immunosuppressive agents, in the course of the induction therapy.
The lower (death-censored) graft survival with ABOi-rTx was in line with a high risk of ABMR. Inclusion of rituximab therapy decreased the risk of ABMR 5 years after transplantation; however, the OR for ABMR was still in the group that had not received rituximab. Polyoma nephropathy was more common after ABOi-rTx than after ABOc-rTX in patients who received rituximab-based desensitisation protocols, which could be explained by viral escape from the immune surveillance. Polyoma nephropathy is probably another reason for the lower graft survival after ABOi-rTx, although we did not find a statistically significant difference in the analysis.
What is the level of evidence provided by this article?
This is a secondary study – with systematic review and meta-analysis. Level evidence – 01.
What are the week and strong points of this study?
– Week : risk of bias
– Strong: Allows generalizing data
Weam Elnazer
3 years ago
summarize the contents of this article
Renal transplantation for patients with ABO incompatibility is becoming more popular as a means of addressing organ shortages. Evidence of its non-inferiority in contrast to ABO-compatible kidney transplantation must be evaluated at both the early and late stages of the disease process, the researchers say.
An observational study with outcome data (at least one year after ABOi-Tx) and an ABO-compatible control group was included in this systematic review and meta-analysis, which was published on December 31, 2017.
Methods: In order to be included, trials on recipients of ABOi-Tx had to include an ABO-compatible control group, as well as outcome data on at least graft or recipient survival with at least one year of follow-up available.
Case reports, editorials, reviews, and letters were all excluded, as were animal studies, meeting papers, studies that we’re unable to extract data, non-renal solid organ and bone-marrow transplant studies, and dead donor ABOc-Tx. Case reports, editorials, reviews, and letters were all excluded.
The information in this study was derived from previously published papers.
At 1, 3, 5, and more than 8 years following transplantation, the primary outcomes were all-cause death and graft survival, respectively.
Finding: ABOi KT treated with rituximab against ABOc KT: At the first and third years, mortality rose but remained stable after that. Survival of filtered grafts is comparable to death.
At 1 and 3 years, the risk of AMR is higher, but at 5 years, the risk is the same. ABOi KT with or without rituximab against ABOc KT:
At the ages of 1, 3, and 5 years, mortality rose, and the trend remained similar at the age of 8. Graft survival was decreased at 1, 3, and 5 years after transplantation when death was filtered out.
An increased risk of CMV and sepsis, with an equal incidence of Polyoma nephropathy, urinary tract infections, and pneumocystis infections.
Level of evidence: Level 1
What are the weak and strong points of this study?
-a few elements from the main outcome sets were included in the original investigations and were thus able to be examined.
There were no studies included in the meta-analysis that reported on other critical categories such as cardiovascular disease, graft function stability over time, diabetes, or relevant patient-reported outcomes.
-The research cohorts included in this analysis were very heterogeneous, with significant differences in donor and recipient ages as well as immunological risk factors.
-The majority of the studies did not describe differences in patient variables that can have an impact on transplantation outcomes, such as frailty status, length of dialysis before transplantation, cardiovascular disease load, and primary illnesses.
Strong point: high level of evidence and a large number of studies and a variety of populations.
mai shawky
3 years ago
· Summary:
· This is a systematic review & meta-analysis of many observational studies from different populations of adults & pediatrics.
· The primary outcome is all-cause mortality & graft survival at 1, 3, 5, >8 years after transplantation.
· ABO-i transplantation has higher mortality at 1, 3, 5 year post transplant which can be attributed to intense immunosuppression from desensitization treatments. However, graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants.
· At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants.
· The risk of infections & surgical complications was higher in ABO-i vs ABO-c.
· TCMR rates was not different between both groups, however the rate of AMR was higher in ABO-i vs ABO-c transplants.
· It is last option in case of failure of PKD to get compatible donor.
· Q2 . level of evidence: Level I
· Q3. Week points:
· The incidence of many complications as cardiovascular disease, stability of graft function & diabetes were not addressed.
· it depends on observational studies, no randomized controlled trials.
· No comparison as regard different immunosuppressive regimen used.
· Strong points:
· No publication bias regarding the mortality outcome.
· The meta-analysis was conclusive regarding the mortality at 1 year, 5 years.
kumar avijeet
3 years ago
Summary of this article-
1.ABOi tx is a/w higher 1yr,3yr,5yr mortality but not 8yr mortality as compared to ABOc tx.(due to overimmunesuppression- infections)
2.Death censored and uncensored graft survival is lower in ABOi tx than ABOc tx at 1yr,3yr,but only death uncensored graft survival at 5yr is lower not death censored with no change of graft survival at 8yr between ABOc and ABOi tx.(mainly due to ABMR,polyoma nephropathy)
3.Though sepsis is more common in ABOi tx than ABOc tx but no difference in incidences of uti,pcp,bkv and cmv infections in between the two groups even though this difference even not exist between two grps whether recieved rtx or not in ABOi tx.(though bit of contradictory but cannot be ascertained on the basis of varied populations and in some studies rtx is more a/w with bkv nephropathy)
4.Greater no of surgical complication (hematoma,lymphocele…)occurs in ABOi tx than ABOc tx.(due to loss of coagulation protein in plasma exchange)
5.More no of ABMR occurs in ABOi tx than ABOc tx with simmilar incidence of TCMR in both the groups with more abmr in non rituximab group than rituximab group in ABOi tx.(due to ABO ag barrier)
6.whether rituximab given or not will not change the fate of patient and graft after 5yrs,but death censored graft survival is lesser at 1yr,3yr in ABOi tx group who were not recieved rituximab than who recieved rituximab.(due to less ABMR)
LEVEL OF EVIDENCE IS 1
LIMITATION OF THIS STUDY
A.not a rct
B.different immunesuppressive protocol
C.other domain like CVS,DM,graft outcome not addressed
D.used allmost observational studies
E.different method used for ab titre, ab removal
F.observational period is shorter than 5yrs in many studies, so very grey zone to comment above 5yrs outcome.
STRONG POINTS
A.varied population group included
B.high level of evidence.
SO CONCLUDING that ABOi tx will decrease the waiting time with increases the organ pool, but infection still a alarming point which require lesser immune suppression with rejection ,which still needs kidney paired donation before ABOi tx.
Theepa Mariamutu
3 years ago
ABOi vs ABOc
ABOi KT were associated with lower patient survival at 1,3 and 5 years while comparable to ABOc KT after 8 years post-transplant. ABOi that were not given rituximab had lower patient survival at 5 years than those with ABOc KT. The increased mortality is due to intensive immunosuppression causing increased infections and sepsis, especially with high dose rituximab. ABOi KT was associated with lower death censored and death uncensored graft survival at 1- and 3-years post-transplant while death censored graft survival was comparable to ABOc KT after 5 years and death uncensored graft survival was like ABOc KT after 8 years. Lower graft survival is due to increased AMR and polyoma nephropathy. ABOi KT had increased incidence of sepsis, but similar rates of UTI, CMV, BK virus and Pneumocystis jirovecii pneumonia. ABOi KTwere associated with increased surgical revisions, although there was no difference in bleeding or hematoma, lymphocele, or ureteral complications. There was increased risk of AMR in ABOi group, although the rates of overall rejections, T cell mediated rejections and borderline rejections were similar.
ABOi KT using rituximab VS ABOc KT:
· Mortality increased at 1 and 3 years, but similar after that
· Death censored graft survival similar
· Increased risk of Polyoma nephropathy, but similar risk of CMV, sepsis, UTI and pneumocystis infections
· Increased risk of AMR at 1 and 3, but similar at 5 years
ABOi KT w/out rituximab VS ABOc KT:
· Mortality increased at 1, 3 and 5 years, similar after 8 years.
· Death censored graft survival lower at 1,3- and 5-years post-transplant.
· Increased risk of CMV and sepsis with similar rates of Polyoma nephropathy, UTI and pneumocystis infections
· Significantly Increased risk of AMR.
Level 1 evidences
Strong points
large number of studies from different aspects to allow diversity of the patients and results.
Weak points
lack of RCTs
endpoints not measured- cardiovascular risk, DM, graft function stability
Various protocols of immunosuppression
study follow up was 5 years only
Huda Al-Taee
3 years ago
Summarise this article
ABO-incompatible renal transplantation is increasingly used to overcome organ shortages. Evidence about its non-inferiority in comparison with ABO-compatible renal transplantation needs to be analysed at early and late time points.
Methods: a systematic review and meta-analysis of observational studies published till Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-Tx and included an ABO-compatible control group.
Searching Methods:
Cochrane Central Register of Controlled Trials (CENTRAL).
Embase Ovid.
MEDLINE Ovid.
PubMed.
Trials on recipients of ABOi-Tx were assessed if an ABO-compatible control group was included and if outcome data on at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-Tx.
Data were extracted from published reports.
Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
Data analysis:
1264 studies were screened.
1121 studies were excluded
143 abstracts reviewed
90 articles excluded
51 full-text articles reviewed
16 articles excluded
40 studies including 49 patient groups were identified.
65063 patients were eligible for analysis, 7098 of whom had undergone ABOi-Tx.
The risk of bias was assessed by the use of the Newcastle-Ottawa Scale because of the absence of RCTs.
The summary estimate was calculated using Review Manager version 5.3.
The statistical heterogeneity was identified by forest plots.
Findings:
Compared with ABOc-Tx, ABOi-Tx was associated with significantly higher 1-year, 3 years and 5 years mortality.
Death-censored graft survival was lower with ABOi-Tx than with ABOc-Tx at 1 year and 3 years only.
Graft losses were equivalent to that of ABOc-Tx after 5 years and patient survival after 8 years. No publication bias was detected
There was statistical heterogeneity
Interpretation:
Despite progress in desensitisation protocols and optimisation of ABOi-Tx procedures, excess mortality and loss of kidney grafts were found compared with ABOc-Tx within the first 3 years after transplantation.
Only long-term outcomes after 5 years yielded equivalent survival rates and organ function.
Awareness of the increased risks of infection, organ rejection, and bleeding could improve the care of patients and promote efforts toward paired kidney exchange programmes.
What is the level of evidence provided by this article?
Level I
What are the weak and strong points of this study?
Limitations:
Endpoints did not address all consented core outcome domains for studies of kidney transplantation.
Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
Fewer data were available for the analyses of clinical outcomes after 5 years.
the possibility of patient cohorts included in national registry analyses as well as smaller single-centre studies could not be ruled out.
An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
Differences in patients’ characteristics that might have an effect on transplantation outcomes.
Strong points:
high level of evidence
the results will encourage clinicians, healthcare providers, and health policymakers to facilitate and expand the network of kidney exchange programmes as an alternative to ABOi-Tx.
Sahar elkharraz
3 years ago
This article is systemic review and meta analysis study involving 40 studies and large number of population more than 65000 patients to investigate differences between ABOI and ABOc renal transplant in base of graft survival, patients survival and infectious and non infectious complications related to ABOI.
This article shows increase incidence of ABMR in those with ABOI who not receive rituximab as part of desensitisation protocol and worse graft survival in those patients in comparison to ABOc rt. also decrease patients survival in ABOI because high incidence of sepsis due to intensified immunosuppressive drug, However no significant difference in related to urinary tract infection and CMV or BK polyomavirus.
Also shows increase incidence of bleeding and hematoma due to plasma pharesis and immunoadsorption in patients with ABOI renal transplant and there’s increase risk of lumphocele and infected wounds in dose patients with ABOI renal transplant.
PKD better than desensitisation protocol in ABOI.
This article evidence 1
weak point / This article is observation study
it’s not randomised control trials
system review less than 5 years
No assessed age of patients/ primary disease/ time of waiting list and long time staying on dialysis / cardiovascular disease and diabetes.
Not assessed different desensitisation protocol
strong point large size of population
address survival of graft and patients survival and complications in ABOI in comparison to ABOc
Amit Sharma
3 years ago
· Summarise this article
ABO incompatible transplantation has increased transplant numbers and reduced waiting times for a kidney transplant. This systematic review was done to analyse the graft outcomes in ABO incompatible transplants vis-à-vis ABO compatible transplants.
The review included 40 studies with more than 65000 patients out of which more than 7000 patients underwent ABO incompatible transplant. Patient and graft survival at 1, 3 , 5 and more than 8 years was assessed.
ABO incompatible transplants were associated with lower patient survival at 1,3 and 5 years while patient survival was similar to ABO compatible transplants at more than 8 years post-transplant. Patients who were not given rituximab had lower patient survival at 5 year than those with ABO compatible transplants. The increased mortality is due to intensive immunosuppression causing increased infections and sepsis, especially with high dose rituximab.
ABO incompatible transplant was associated with lower death censored and death uncensored graft survival at 1 and 3 years post-transplant while death censored graft survival was similar to ABO compatible transplants after 5 years and death uncensored graft survival was similar to ABO compatible group after 8 years. Lower graft survival is due to increased AMR and polyoma nephropathy.
ABO incompatible transplants had increased incidence of sepsis, but similar rates of UTI, CMV, BK virus and Pneumocystis jirovecii pneumonia. ABO incompatible transplants were associated with increased surgical revisions, although there was no difference with respect to bleeding or hematoma, lymphocele or ureteral complications.
There was increased risk of AMR in ABO incompatible group, although the rates of overall rejections, T cell mediated rejections and borderline rejections were similar.
Comparing ABO incompatible transplants using rituximab with ABO compatible transplants: 1) Mortality increased at 1 and 3 years, similar later 2) Death censored graft survival similar 3) Increased risk of Polyoma nephropathy, but similar risk of CMV, sepsis, UTI and pneumocystis infections 4) Increased risk of AMR at 1 and 3 , but similar at 5 year
Comparing ABO incompatible transplants without using rituximab with ABO compatible transplants: 1) Mortality increased at 1, 3 and 5 years, similar after 8 years. 2) Death censored graft survival lower at 1,3 and 5 years post trasnplant. 3) Increased risk of CMV and sepsis with similar rates of Polyoma nephropathy, UTI and pneumocystis infections 4) Significantly Increased risk of AMR. · What is the level of evidence provided by this article?
This is a systematic review and meta-analysis. Level of evidence is level 1.
· What are the weak and strong points of this study?
The weak points of the study are:
1) The study includes observational studies only. No RCT (randomized controlled trial) was included in the review.
2) No standard protocol was used in the different studies, hence it is difficult to compare outcomes especially regarding the effects of desensitization, immunosuppression and titre threshold.
3) Detailed datasets were not available, including patient characteristics like dialysis vintage, primary disease, cardiovascular and frailty status etc.
4) The patient cohorts were heterogeneous.
5) Various important domains, including stability of graft function, cardiovascular disease, diabetes, patient-reported outcomes could not be assessed.
The strong points of the study are:
1) The heterogeneity of the patient cohort is a strong point as the results of the meta-analysis are applicable on a large population/ geographical area.
2) Despite lack of detailed datasets, this meta-analysis gives important insights in the graft and patient survival in ABO incompatible transplants, coming to the conclusion that ABO compatible transplants have advantage over ABO incompatible transplants and hence kidney paired programs should be encouraged.
Mohamed Mohamed
3 years ago
III. Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis Summarise this article This is a systematic review & meta-analysis of a large number of observational studies published up until Dec 31, 2017. It included a diversity of population of both adults & pediatrics. The primary endpoints were all-cause mortality & graft survival at 1, 3, 5, & >8 years after transplantation. ABO-i has a higher mortality at 1-, 3- & 5-year compared to ABO-c transplantation. The high mortality was related to the intense immunosuppression from desensitization treatments. Graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants. At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants. The risk of infections & surgical complications was higher in ABO-i vs ABO-c
TCMR rates was not different between both groups, however the rate o AMR was higher in ABO-i vs ABO-c transplants. Conclusion: Compared to ABO-c living donor, ABO-i renal transplantation is worse in all clinical outcomes. KPD is favored in place of ABO-i transplantation. ================================================ What is the level of evidence provided by this article? Level I ================================================ What are the week and strong points of this study?
Week points:
– Some of the consented outcomes were not addressed in the endpoints. These included cardiovascular disease, stability of graft function, & diabetes.
– The results were not robust >5 years after transplantation.
– No randomized controlled trials.
– The effect of specific induction 8 desensitization regimen could not be assessed.
Strong points:
– No publication bias regarding the mortality outcome.
– The meta-analysis was conclusive regarding the mortality at 1 year, 5 years (inconclusive for mortality at >8 years).
Abdulrahman Ishag
3 years ago
The aim of the study;
was to investigate differences in outcome after ABOi-rTX and ABOc-rTX .
The type of the study;
This systematic review and meta-analysis .
Population;
More than 65 000 patients originating from the USA, Europe, Asia, and Australia . 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx.
Exclusion criteria;
included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-rTx.
The primary end points;
were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
The result of the study ;
Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality 3 years and 5 years following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year and 3 years only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
what is the level of evidence provided by this article ?
Level 1
What are the weak and strong points of this study ?
1-Only some items of the core outcome sets were encompassed in the primary studies and could be analyzed.
2-Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient- reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
3-Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
4- The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years.
5-An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
6-Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
7- Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
8- Ethical considerations and administrative barriers exist and have to be taken into consideration.
Ibrahim Omar
3 years ago
Summarise this article :
ABO incompatible renal transplanation (ABOi-rTx) is increasingly done to overcome the growing problem of organ shortage. however, the outcome is still to be well-defined in comparison to ABO compatible renal transplantation (ABOc-rTx)
this article is a systemic review and meta analysis of a large number of studies that were published up to 2017.
the 1ry endpoints were all cause mortality and graft survival at 1,3,5 and 8 years post-transplantation.
the results were as following :
1- ABOi-rTx involves a significantly higher mortality at 1,3 and 5 years post-transplantation, in comparision to ABOc-rTx. however, mortality rates and so patient survival were almost equivalent in both groups, 8 years post-transplantation.
2- ABOi-rTx involves a lower graft survival at 1,3 years post-transplantation, in comparision to ABOc-rTx. however, graft losses and so graft survival were almost equivalent in both groups, 5 years post-transplantation.
ABOi-rTx involves serious desensitization protocols that have serious side effects, including increased risks of infection and graft rejection as well as surgical complications.
efforts toward paired kidney donation programs should be maximized and combined with desensitization protocols to get more favourable outcomes.
What is the level of evidence provided by this article?
I
What are the week and strong points of this study?
the strong points include the very large number of included studies from multiple centres and the meta analysis model of studying.
the weak points include the lack of proper randomization and and also the other patient characteristics including all comorbidities.
Mohamad Habli
3 years ago
ABOi renal transplantation provides novel options for patients in need of a transplant organ with a living donor. This is a systematic review and meta-analysis of observational studies with level of evidence 1, from 40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia, published up until Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-rTx and included an ABO-compatible control group.
Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
Results
• Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality, 3 years, and 5 years. Following transplantation. Meta-analysis clearly shows that even with the most advanced desensitisation protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX.
• Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year.
• Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
• Higher rates of bleeding events are more common after ABOirTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis or highvolume plasma exchange, or both.
• The risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant conditioning regimens.
The observed higher early mortality after ABOi-rTx than after ABOc-rTX could be overcome by refining the initial immunosuppressive protocols and individualising the immunosuppressive therapy.
Weak points
– No randomized controlled studies identified in the search
– Cardiovascular disease, graft function stability, and diabetes were not all mentioned as outcomes in most of the studies.
– Desensitisation protocols used were not unified which makes impossible to assess their outcomes.
– The followup of most studies is for less than 5 y
– Lack of heterogenicity of studied population
– Inaccuracy of determining the accurate time of occurrence of complications
– ABOc-rTx from deceased donors was not included in the study
Strong points
– Large number of cases and studies were enrolled
– It included outcome data for graft or recipient survival available for at least 1 year or more follow-up.
– Statistical heterogenicity was detected by inspecting the forest plots and the estimates of the diversity (D²) and inconsistency (I²) statistics.
– In this study they used calculations to enable the statistical inference concerning a cumulative meta-analysis that has not yet reached the required information size to be notice.
– The funder of the study did not interfere in the study details.
– Absence of publication bias with regard to the mortality outcome
Abdul Rahim Khan
3 years ago
With increasing organ shortage the trend to do more ABOi- KT has emerged . The outcome of ABOi- KT and ABOc- KT needs to be assessed at early and late points. In this sytemic review the authors have investigated the difference in outcome of ABOi- KT and ABOc- KT. in this review data was analyzed from published reports.
Methodology.
This was a systemic review and meta analysis looking at outcome at>= 1 year post ABOi- KT and ABOc- KT. Data was searched on Medline Ovid , Pubmed, Central Embass Ovid. Inclusions– all studies comparing ABOi- KT and ABOc- KT
Exclusions– Case reports, Editorials, letters, meeting reports and studies where data could not be extracted .
Primary End point– Mortality at 1,3,5 and 8 years post KT
They used a fixed effect model if I2 value was 0 and both random and fixed effect model if I2
was more than 0.
Results.
About 40 studies were analyzed and it was noted that outcome was inferior in ABOi- KT as compared to ABOc- KT as regards graft survival and mortality. Graft loss were almost similar at 5 years and patient survival was similar at 8 years.
Conclusions.
In short term the outcome of ABOi- KT was poor that ABOc- KT
Level of evidence -1
Weakness of study
Short duration and non randomization
Did not include ABO compatible deceased donors.
onset of infectious and non infectious complications could not be determined
Didn’t assess the effectiveness of specific desensitization protocols
Strength of study
Meta analysis
Case reports, Editorials, letters, meeting reports and studies where data could not be extracted .
Ben Lomatayo
3 years ago
Introduction
Renal transplantation is the treatment for patients with ESRD [1-3]. How ever many patients can not make it to transplantation due to shortages of donors and they keep accumulating in the transplant waiting list. ABO-i Tx is becoming encouraging option to increased the pool of living kidney donors. This study was conducted to to address the differences in outcome between ABOi-rTX and ABOc-rTX
Methodology
systematic review and meta-analysis of observational studies publish between Jan27,1998 and Set 1,2017 was looking at reported outcome data >=1 year follow up following ABOi-rTX and ABOc-rTX control group. The literature was searched by the CENTRAL, Embase Ovid, MEDLINE Ovid, and PubMed. All studies of ABOi-rTX and ABOc-rTX control group were evaluated. This study excluded ; case reports, editorials, review and letters, meeting reports, animal studies,deceased donor ABOc-rTX, non-renal solid organ and bone marrow transplant studies, and studies where data cannot be extracted. Primary outcomes were all cause mortality and graft survival at 1,3,5 and > 8 years post-transplantation. Fixed-effects model was considered when I2 = 0 and both fixed-effect and random-effects model were considered when I2>0
Results
1264 references were examined and 40 studies finally analyzed
>65000 patients, 7000 transplanted across ABO systems barriers were captured
Inferior outcomes was seen in ABOi-rTX compared to ABOc-rTX ; 1. Higher mortality rates at 1 year(P<0.0001) after transplantation. 2. Poor death-censored graft survival at 1 year
Graft loss were similar at 5 years
Patient survival were similar at 8 years
No evidence of publication bias
Conclusion
Despite the advances and progress in the techniques of desensitization protocols this meta-analyses showed significant mortality and grafts loss associated with ABOi-rTX compared to ABOc-rTX at least in the short term. The outcomes appeared to be the same after 5 years.
Level of evidence = 1
Limitation of the study
1.Good points , this is systematic review and meta-analysis
ABOc-rTX is superior to ABOi-rTX in the first 5 years
Refinement & individualization of the immune-suppression should be considered to decreased high morality of ABOi-rTX
Preemptive antibiotics and virostatic therapy consideration
Surveillance of tendency should be optimized after PP or AI
ABOi-rTX may better than remaining on dialysis
Paired kidney exchange is a valuable to overcome ABOi-rTX barriers
2.Weak points
This study didn’t cover all consented core outcome domains for studies for kidney transplantation [86, 87]
No reports from the included studies about cardiovascular disease, stability of graft function, diabetes or meaningful patients reported outcomes
Variation in immune-suppression desensitization protocol between studies,therefore is not possible to evaluate the effect of specific induction & desensitization protocol
Most included studies are of short term duration < 5 years, and clinical outcomes after 5 years cannot be analyzed
The exact time of complications( infections,surgical, and immunological) were not reported
Wide range of heterogeneity among studies
No information about differences in baseline patient characteristics e.g. frailty status, dialysis vintage, cardiovascular disease burden, & primary disease outcome
The analysis didn’t include ABOc-rTX from deceased donor
Manal Malik
3 years ago
continue
versus the group without rituximab;
promote effective PKDE program to over come the disadvantages of ABOi -KT such as infection ,rejection and bleeding . level of evidence 1 weakness of this study
short time duration of this study
not randomized control trial
exclude deceased ABOc -KT in the study strength of the study
meta analysis systemic review.
proper data collection as excluded case report and others in proper data.
large number of studies comparing more than 65000 patients and 7000 whom undergo ABOi-KT were identified.
no publication bias was detected.
Manal Malik
3 years ago
summary
ABO incompatibility is increasing used to overcome organ shortage.
this systemic review investigate difference in out come after ABOi-rTX and ABOc-rTX.
Data were extracted from published reports.
primary endpoint were all cause mortality and graft survival at 1.3.5 and 8 years after transplantation
comparing ABOi-rTX and ABOc-rTX the result is higher mortality 1.3.5years following transplant
mortality attributed mainly to intensify immunosupressin therapy which result in infection such as viral (CMV) and bacterial ,in addition to bleeding mainly realted to use of anti coagulation during plasmapharesis
also death-censored graft survival has lower with ABOi-rTX with ABOc-rTX at 1 year and 3 year . only graft loss were equivalent to that of ABOc-rTX after 5 years and patient survival after 8 year.
incidence of AMR is higher in patient with ABOi- than ABOc years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group versus the group without th
.
Doaa Elwasly
3 years ago
1- Summary
Smaller studies adressing patient and graft outcome after ABOi-rTx did not show any differences compared with living donor ABO-compatible renal transplantation (ABOc-rTx), larger registry data results were equivocal.
This study is a systematic review and meta-analysis of the published data to evaluate if the effects of ABOi-rTx in terms of graft survival, patient survival, and infectious and non-infectious complications are comparable to that of ABOc-rTx, taking into consideration the different desensitisation strategies .
Results
It showed that ABOi-rTx was associated with a higher risk of 1-year , 3-year and 5-year mortality , but not of 8-years or more mortality when compared with ABOc-rTx .
Sepsis was higher after ABOi-rTx than after ABOc-rTx but there was no statistically significant difference in the risk of urinary tract infections , cytomegalovirus infection , BK polyomavirus infection , and P jirovecii pneumonia.
No significant difference in the number of ABOi-rTx patients with surgically treated lymphocoeles or ureteral complications and those with ABOc-rTx meanwhile surgical revisions for hematoma ,lymphocele and surgical complications were more in ABOi-rTx group.
No significant difference between both groups regarding overall , borderline , or T-cell mediated rejections but ABMR rate was higher after ABOi -rTx than after ABOc-rTx
Rituximab-based versus non rituximab-based desensitation protocols revealed higher 1-year and 3-year mortality after ABOi-rTx than after ABOc-rTx apart from the initial desensitisation protocol
5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group versus the group without the rituximab.
In groups with rituximab usage in desensitisation, death-censored graft survival at 1 year and 3 year was equal between ABOi-rTx and ABOc-rTx groups while in cases of densenstisation without rituximab usage death-censored graft survival at 1 year and 3 year was worse in the ABOi-rTx than ABOc-rTx groups.
Rituximab usage in desensitisation protocols or not didnot reveal significant difference regarding graft survival data after 5 years between the 2 groups.
In non-rituximab-based desensitisation protocols ,sepsis and cytomegalovirus infections risk after ABOi-rTx was significantly higher than after ABOc-rTx, but no difference was seen between the 2 groups in those who received rituximab-based desensitisation protocols
A trend for higher risk for polyoma nephropathy was noticed after ABOi-rTx than after ABOc-rTx in patients who received rituximab-based desensitisation protocols.
Concerning P jirovecii pneumonia and urinary tract infections, no significant differences were detected between ABOi-rTx and ABOc-rTx with either of the desensitisation protocols.
A higher risk of ABMR after AB0i-rTx than after AB0c-rTx with both desensitisation protocols was noticed but it was significantly lowered if rituximab based protocol was applied.
Discussion
The study demonstrated that ABOc-rTx has better outcome than ABOi-rTx in the first 5 years after transplantation but after 8 years equal otcomes was noticed for survivors of the 2 groups.
In rituximab based protocols mortality with ABOi-rTx was only seen within the first 3 years, and death-censored graft survival became similar to that of ABOc-rTx within the first year.
The study showed that with the introduction of different advanced desensitisation protocols, mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX due to overimmunosuppression , life threatening infection and higher risk of bleeding and surgical complications ,this can be solved by individualising immunsuppresion protocol , as in some studies concluding that using lower doses of immunosuppression can decrease infection risk and won’t increase the rejection risk ,leading to favourable overall outcome.
Paired kidney exchange program is the other choice for cases fit for ABOi rTx
2- level of evidence is I
3-Strong points are
-that the systematic review and the meta-analysis were done according to the most accepted practices regarding assessment of study quality and risk of bias.
-Large number of cases and studies were enrolled
-It included outcome data for graft or recipient survival available for at least 1 year or more followup .
-Statistical heterogenicity was detected by inspecting the forest plots and the estimates of the diversity (D²) and inconsistency (I²) statistics.
-In this study they used calculations to enable the statistical inference concerning a cumulative meta-analysis that has not yet reached the required information size to be noticed
-The funder of the study did not interfere in the study details.
-Absence of publication bias with regard to the mortality outcome Weak points are
-the evidence given has the inherent drawbacks of observational studies and there was no randomised controlled studies identified in the search
-Not mentioning all consented fundamental outcome items for studies of kidney transplantation as cardiovascular disease, graft function stabiliy, and diabetes.
-Ununified desensitisation protocol used rendered it impossible to assess their outcomes.
-Most studies followed the cases for less than 5 y and small centre studies were not excluded
-Lack of heterogenicity of studied population
-Inaccuracy of determining the accurate time of occurrence of complications
-ABOc-rTx from deceased donors was not included in the study
Heba Wagdy
3 years ago
Summary
ABO incompatible (ABO-i) kidney transplant is increasing to overcome the shortage of organs from deceased donors, this was enabled by desensitization strategies.
Results of studies comparing the outcome of ABO compatible (ABO-c) and ABO-i kidney transplants are controversial.
The safety and outcome of ABO-i kidney transplants are not well determined.
A meta-analysis and systemic review of observational studies reporting the outcome of ABO-i kidney transplant after one year or more of follow up and included ABO-c transplants as control group.
Predefined primary outcomes were graft survival and all-cause mortality at 1,3,5 and 8 years post transplant.
secondary outcomes were infectious and non infectious complications and graft rejections. It showed that
ABO-i renal transplant is associated with poorer graft survival and higher immunological risk.
ABO-c transplants are more beneficial than ABO-i transplant in the first 5 years with similar long-term outcome.
Patient mortality was higher in first 5 years with ABO-i renal transplant than with ABO-c transplants.
ABO-i transplants are associated with higher risk of AMR.
ABO-i transplants had higher rates of bleeding events, wound infection, hematomas and surgical revisions.
Decrease of initial immunosuppression may decrease early mortality rates in selected patients
ABO-i transplants are associated with significant higher risk of polyoma nephropathy than in HLA incompatible transplants.
ABO-i transplants with rituximab based desensitization protocols have the same risk of AMR as in ABO-c transplants 5 years post transplant. Type of study meta-analysis systemic review level of evidence 1 Strength
Meta-analysis systemic review
Excluded case reports, editorial reviews and studies with unextractable data Limitations
Couldn’t analyze all outcome data in studies of kidney transplantation.
Couldn’t assess the effectiveness of specific desensitization regimens.
Most studies have short observation period less than 5 years so failed to analyze the outcome after 5 years.
Possibility of duplication due to inclusion of patient cohorts in national registry analysis and smaller single-centre studies.
Didn’t state the time of complication post transplant.
Patients characteristics were not reported in most studies and they may affect transplant outcome.
Didn’t include ABO-c transplants from deceased donors.
Mohamed Saad
3 years ago
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis.
This systematic review and meta-analysis for 40 eligible studies for assessing clinical outcomes of ABOi-rTx in comparison with ABOc-rTx which comprising more than 65000 patients, 7000 of whom had undergone ABOi-rTx.
All studies were published between Jan 27, 1998, and Sept 1, 2017 were included considered to be drawbacks of observational studies and references identified by database searches. Introduction:
ABO-incompatible renal transplantation is considered one option which contributes to shorten the time of potential kidney recipients on waiting list specially with promising graft and patients survival with the new strategy of desensitization specially for patients with end-stage renal disease presenting with a living donor with an unsuitable blood group. Data analysis:
Predefined primary outcomes were graft survival and all-cause mortality at 1, 3, 5, and more than 8 years after transplantation.
Secondary outcomes were infectious and non-infectious complications, and graft rejections. Results:
=37 (65 063 participants) for 1 year.
=27 (44 213 participants) for 3 years.
=15 (56 640 participants) for 5 years.
=Three studies (11 039 participants) for more than 8 years were included in the analysis of mortality after transplantation.
* ABOi-rTx was associated with a higher risk of 1-year mortality , 3-year mortality , 5-year mortality, but not of 8-years or more mortality.
* At 1 year, death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx , as was death-uncensored graft survival.
* At 3 years, death-censored and death-uncensored graft survival was lower after ABOi-rTx than after ABOc-rTx.
* Death-uncensored but not death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx.
* The proportion of patients with sepsis was higher after ABOi-rTx than after ABOc-rTx.
* A greater proportion of patients who had ABOi-rTx had surgical revision than those who had ABOc-rTX, bleeding or hematomas , and lymphoceles.
* No significant difference between treatment groups was observed in overall , borderline , or T-cell mediated rejections
* By contrast, the proportion of patients with ABMR was higher after ABOirTx than after ABOc-rTx.
* Higher 1-year and 3-year mortality after ABOi-rTx than after ABOc-rTx regardless of the initial desensitization protocols (with or without Rituximab).
* There was a trend for a higher risk of ABMR after AB0i-rTx than after AB0c-rTx with both desensitization protocols. Discussion:
Systemic review and meta-analysis of 40 studies including more than 65000 patients which generally shown The clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation.
Only long-term data after 8 years indicate equal performance of the procedures for survivors.
Statistical analysis shows that even with the most advanced desensitization protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX so PKD should be considered as a great option before shifting to ABOi TX or be complementary together.
Higher rates of surgical complications specially bleeding events are reported after ABOirTx than after PEX or immunoadsorption.
Higher early mortality after ABOi-rTx than after ABOc-rTX could be overcome by refining the initial immunosuppressive protocols and some studies with lowering IS has the better outcome with less infectious complications and without increased incidence of acute rejection.
The risk of ABMR with rituximab-based desensitization protocols was clearly reduced (in comparison with splenectomy) and the risk of ABMR in the ABOi-rTX group was similar to that in the ABOc-rTX group 5 years after transplantation if rituximab was initially used.
Similar results were obtained in immunologically high-risk recipients of ABOc-rTx given rituximab within the course of induction therapy.
The alternate option to ABOi-rTx would be paired kidney exchange, or even more complex scenarios have been successfully managed, such as three-way and multiple-way kidney exchanges. Our results should encourage clinicians, health-care providers, and health policy makers to facilitate and expand the network of kidney exchange programs. a systematic review and meta-analysis Level of evidence I. Limitations or weakness:
– Cardiovascular disease, stability of graft function, diabetes, or meaningful patient reported outcomes, could not addressed.
– The observational periods were shorter than 5 years and so less data were available for the analyses of clinical outcomes after 5 years. Strength points:
– meta-analysis level evidence .
-Large number of studies and large number of patients.
-multiple centers international experience.
Ban Mezher
3 years ago
Systemic review & meta-analysis, level 1
Due to shortage of both deceased & live donor pools, the ABOi transplantation became an accepted option to overcome this shortage.
Aims of the study:
assess the effect of ABOi transplantation on graft survival, patient survival, infectious & non infectious compared to ABOc transplantation.
effect of different desensitization protocols.
Method:
It is a systemic review & meta-analysis ( PROSPERO protocol. Include 40 studies (65000 patients) of pediatric & adult ABOi transplantation with AbOc patients as control group from USA, Europe, Asia & Australia, with follow-up for >1 year.
Exclusion include case report, editorial, review & letters, animal studies, meeting paper, non renal solid organ transplant & bone marrow transplant & non English studies.
Primary outcome: graft survival & all cause mortality at 1,3,5 & > 8years.
Secondary outcome: infectious( sepsis, UTI, CMV, BK virus, P. jirovecii ) & non infectious ( surgical revision, hematoma, lymphocyte, ureteral) complication & graft rejection.
Results & discussion:
Statistical analysis shows that the benefit of ABOc-T is more than ABOi-T in first 5 years post transplant.
patients mortality was higher in ABOi-T in first 5 years which may be due to result of over immunosuppression of immune system.
ABOi-T associated with higher rate of bleeding due to changes of coagulation system after PP.
ABOi-T associated with more post operative surgical complication
serious infection was associated with use of rituximab( high dose) during desensitization or during peri-transplant conditioning.
High rate of mortality among ABOi-T patients which can be overcome by using low dose of rituximab, no rituximab, or no PP during induction phase or using lower MMF dose in maintenance phase without increase incidence of acute rejection.
High risk of BK associated nephropathy among ABOi-T patients, the risk is significantly higher than HLA incompatible transplantation.
Risk of ABMR in patients with rituximab was reduced & it comparable to ABOc-T 5 years after transplantation.
Limitations of the study:
endpoint of the study didn’t address all consented core outcome domain.
Different immunosuppressant regime in different studies making difficult to assess effect on specific induction & desensitization regimes.
Short observational period <5 years for most of studies.
accurate onset of infectious & non infectious complication can’t be determined
differences in patients characteristic may had an effect on transplant outcome.
heterogeneity of included studies
Sherif Yusuf
3 years ago
This is a systematic review and meta-analysis of observational studies including 65 063 patients
Addressing graft and patient survival 1, 3, 5, and more than 8 years after transplantation In ABO-incompatible transplantation
Results and conclusion
ABOi when compared to ABO-compatible transplantation is associated with the following :
Higher risk of ABMR but not TCMR
Lower graft survival in the first 3 years post transplantation, but long term graft survival is comparable to ABO compatible transplantation
Lower patient survival at 1, 3, and 5 years post transplantation but long term patient survival at 8 years is comparable to ABO compatible transplantation
Lower Death-censored graft survival at 1 and 3 years but not at 5 years post transplantation
Bleeding is the most common surgical complications related to ABO I transplantation due to removal of clotting factors by plasmapharesis
Surgical revisions and lymphoceles are more frequently seen in ABOi transplantation due to unclear cause some relate this to the early initiation of MMF
There is an increase in the risk of infections and sepsis in ABOi when compared to compatible transplantation including pneumonia, UTI, wound infection, PCP, CMV and BK virus, which may be attributed to the use of rituximab
What is the level of evidence provided by this article?
It is a systematic review and meta-analysis, level of evidence I
What are the week and strong points of this study?
The strength of this study arise from its nature as it is a meta-analysis study with level I of evidence and including very large pool of patients from different populations
Weakness arise from the lack of addressing other endpoints, absent information regarding if the recipient has comorbid conditions such as DM and cardiovascular disease, different protocols used so increasing bias when interpreting the results, moreover most of the studies duration is not exceeding 5 years
Riham Marzouk
3 years ago
CLINICAL OUTCOMES AFTER RENAL TRANSPLANTATION INVOLVING ABOI
Mortality in the patients transplanted from ABO incompatible donor is higher at 1, 3 and 5 years post-transplant than the patients transplanted from ABO compatible donor, and become the same at 8 years post transplant, this mostly related to side effects of heavy immunosuppression given to these patients like infections either bacterial and viral like BK virus, CMV, coagulation disorders.
the incidence of AMR is higher in the patient with ABO incompatible donor than those with ABO compatible donor in spite of heavy immunosuppression and giving rituximab.
level of evidence 1
strong points it is large number of studies from different areas allow diversity of the patients and results.
weak points lack of randomized clinical trials, there are some endpoints not mentioned or addressed by the studies like cardiovascular risk, DM, graft function stability, also different protocols of immunosuppression allow impossible comparison to get right assessment based on specific immunosuppressive protocol, also years of follow up was 5 years only, not extended to be longer than that
Parameters compared between ABOi and ABOc transplant –
graft survival
patient survival
infectious complications
non-infectious complications
systematic review and meta-analysis was done according to the PROSPERO protocol.
Inclusion criteria –
studies of paediatric or adult recipients of ABOi-rTx
if an ABO-compatible control group was included
if outcome data for at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria –
case reports
editorials
reviews and letters
animal studies
meeting papers
studies with unextractable data
non-renal solid organ transplant studies
bone-marrow transplant studies.
Non English articles
40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia were included.
The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation.
Only long-term data after 8 years indicate equal performance of the procedures for survivors.
With use of rituximab instead of splenectomy excess mortality with ABOi-rTx was only seen within the first 3 years, and death-censored graft survival became similar to that of ABOc-rTx within the first year.
patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX due to emergence of life threatening infections due tp over suppressed immune system.
Higher rates of bleeding events are reported after ABOirTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis.
Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles are more common after ABOi-rTx.
The risk of postoperative bleeding appears to be especially high if immunoadsorption is used.
risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination.
Stately to decrease infection risk and mortality include-
reduced dose of rituximab
no rituximab
no plasmapheresis during the induction phase
lower doses of mycophenolate mofetil during the
maintenance phase.
The lower (death-censored) graft survival with ABOi-rTx
was in line with a high risk of ABMR.
Polyoma nephropathy was more common after ABOi-rTx
than after ABOc-rTX in patients who received rituximabbased desensitisation protocols.
The risk of developing polyoma virus-associated nephropathy in patients who have undergone ABOi-rTx is even significantly higher than in recipients of HLA-incompatible kidney transplants.
The improvement in graft survival at 3 years in the
ABOi-rTx group that received rituximab mainly reflects
evolution in the preconditioning procedure.
Patients undergoing ABOi-rTx are at higher immunological risk because of –
re-transplant condition
older age
unrelated donors
more HLA mismatches
higher panel reactive and donorspecific antibody amounts.
risk of ABMR in the ABOi-rTX group was similar to that in the ABOc-rTX group 5 years after transplantation if rituximab was initially used.
Limitations-
endpoints did not address all consented core outcome
domains for studies of kidney transplantation.
Different immunosuppressive protocols were used
between studies, making it impossible to assess the effect
of a specific induction and desensitisation regimen.
The observational periods were shorter than 5 years in most studies.
Duplication of patient data is a possibility.
An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
The alternate option to circumvent ABOi-rTx would be
paired kidney exchange, which has been established in
numerous centres.
Summary of the Article:
ABOi renal transplantation was considered unwise in the past because of ABMR and early graft loss. The long stay, waiting for a compatible donor was the real potentiation toward ABOi-rTX especially after development in the pre-transplant management.
This systemic review and meta-analysis reviewed the registered data up to 2017, looking for the outcome of ABOi-rTX in comparison to ABOc-rTX
Study findings:
· Study findings showed that ABOi-TX had an inferior outcome regarding: patient and graft survival, infectious and non-infectious complications, and graft rejection episodes.
· The refinement in the desensitisation protocols and the implementation of less intensive immunosuppressive regimens improved patient and graft survival.
· Inclusion of rituximab therapy decreased the risk of ABMR 5 years after transplantation.
· Rituximab seems not to be effcient in reducing the concentration of preformed anti- HLA antibodies or preventing the development of de-novo anti-HLA antibodies, both well known and strong risk factors for chronic ABMR and poor graft outcomes.
· The risk for polyoma nephropathy was not lower after ABOi-rTx than after ABOc-rTx in patients who received non-rituximab-based desensitisation protocols. This higher mortality could be a result of side-effects due to an over- suppressed immune system following desensitisation with emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus).
· Polyoma nephropathy is probably another reason for the lower graft survival after ABOi-rTx,
· Higher rates of bleeding events are reported after ABOi- rTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis or high- volume plasma exchange, or both.
level of evidence:
systemic review and meta-analysis; level of evidence I a
The week points in the study:
· The study’s endpoints did not address all consented core outcome domains for studies of kidney transplantation.
· The study didn’t address other comorbidities like cardiovascular diseases, DM and stability of graft function.
· Different immunosuppressive protocols were used between studies.
· The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years.
· An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
· Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
· Diferences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
· The analyses didn’t cover ABOc-rTx from deceased donors.
The strong points in the study:
· Systemic review and meta-analysis.
· 40 studies out of 1216 studies were included in the systemic review.
· The study group was fair enough to conclude that the outcome data for ABOi-rTx within the first 3 years after transplantation are worse than for ABOc-rTx, but the results should not be considered conclusive.
A systematic review and meta-analysis was done to investigate differences in outcome after ABOi-rTX and ABOc-rTX.
This meta-analysis included 40 studies . All studies were published between Jan 27, 1998, and Sept 1, 2017, and included 65063 patients in total. The number of paediatric and adult recipients of ABOi-rTx ranged between ten and 1878 for the included studies, and the number of ABOcrTx recipients ranged between 21 and 26504.
level of evidence provided by this article?
systematic review and meta-analysis : level of evidence 1
The week points of this study
The strong points of this study
the study level 1 evidence systematic review and meta-analysis
with large numbers of studies included large number of patients with different countries and ethnicity.
This systematic review and meta-analysis is based on transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia.
The advent of ABOi-rTx provides novel options for patients in need of a transplant organ with a living donor. For most countries, a paired donation programme
to circumvent the immunological challenge of ABO incompatibility is precluded by law. Thus, ABOi-rTx remains the only option.
This meta-analysis clearly shows that even with the most advanced desensitisation
protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX. This higher mortality could be a result of side-effects due to an oversuppressed immune system following desensitization with emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus)
– endpoints did not address all consented core outcome domains for studies of kidney transplantation. Only some items of the core outcome sets were encompassed in the primary studies and could be analysed.
– Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
– Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
– The observational periods were shorter than 5 years in most studies and
therefore less data were available for the analyses of clinical outcomes after 5 years.
– An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
– Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
– Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis
before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
• What is the level of evidence provided by this article?
Level I
Summary of the article:
This was a systematic review and meta analysis of a large number of observational studies published till Dec 31, 2017. It included different population groups like adults and pediatrics…The study was published in the LANCET in 2019…Outcome data was reported for ABOi renal transplants when compared to ABOc transplants…small case reports and editorials were excluded from inclusion in the meta analysis. It included more than 40 studies from Us, Europe, Asia and Australia….The primary end points were all cause mortality and graft survival at 1,3,5 and >8 years after transplantation….
The meta analysis concluded that ABO-i has a higher mortality at 1-, 3- & 5-year compared to ABO-c transplantation. The high mortality was related to the intense immunosuppression from desensitization treatments.
Graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants.
At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants.
The risk of infections & surgical complications was higher in ABO-i vs ABO-c renal transplants.
TCMR rates was not different between both groups
However the rate Antibody mediated rejection was higher in ABO-i vs ABO-c transplants.
Discussion:
The analysis of the Lancet Metanalysis demonstrates a clear benefit of ABOc renal transplants as compared to ABOi renal transplants at 1,3,5 years….Graft survival and Patient survival improved and equaled ABOc transplants only after 8 years of ABOi renal transplants. This is due to the current desensitization strategies used which is associated with higher incidence of bacterial sepsis and viral infections (Polyoma and CMV)…Various studies have addressed the issue for tailored desensitization to reduced the risk of over immunosuppression….Surgical complications like wound infection, bleeding and lymphocele were more common after ABOi renal transplants. …The use of IA columns have been associated with thrombocytopenia and increased risk of post operative bleeding….The study also emphasizes the need of other studies using rituximab lower dose protocols like 200mg instead of 375mg/m2…Few studies even did transplants even without rituximab…The meta analysis also used the risk of increased risk of BK virus nephropathy which can cause graft loss…..The reason to use rituximab was a reduced incidence of ABMR after transplant….Although this was seen across many observational studies, the side effects of over immunosuppression namely infections and development of PTLD have been reported….
The limitations of the metanalysis was randomized trails were not included…The analysis compared studies using different protocols which used different cut off of Anti A/b titre and different isoagglutinin measurement strategies….Other parameters like cardiovascular diseases, graft outcome were not analyzed…
The evidence of the article is Level 1
Systemic review -meta-analysis of level 1 evidence the ABOi transplantation became an accepted option to overcome the shortage of both deceased & live donor pools .
It is a systemic review that Included 40 studies of ABOi transplantation with AbOc patients as control group from USA, Europe, Asia & Australia, with follow-up for more than 1 year.
Primary outcome: graft survival and all cause mortality at 1,3,5 and 8 years .
Secondary outcome: infections , surgical complications and graft rejection.
Results:
The benefit of ABOc Tx is more than ABOi Tx in the first 5 years post transplant.
patients mortality was higher in ABOi Tx in the first 5 years .
ABOi-T associated with higher rate of bleeding as well as more post op surgical complications .
serious infection was associated with use of rituximab( high dose) during desensitization or during peri-transplant conditioning.
High rate of mortality among ABOi-T patients which can be overcome by using Rituximab As risk of ABMR in patients with rituximab was reduced & it comparable to ABOc-T 5 years after transplantation.
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis.
This is a systematic review and meta-analysis of observational studies with level 1 evidence.
The objective of this systemic review is to study all-cause mortality and graft survival among the ABO incompatible kidney recipients at 1, 3, 5, and more than 8 years after transplantation. This meta-analysis included observational studies published up until Dec 31, 2017, that reported outcome data (at least 1 year of follow-up) after ABO incompatible kidney transplant and ABO-compatible as control group. However, case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABO compatible kidney transplant were excluded. This meta analysis revealed that ABO incompatible kidney transplant was associated with significantly higher 1-year mortality (odds ratio [OR] 2.17 [95% CI 1.63–2.90], p<0.0001; I²=37%), 3 years (OR 1.89 [1.46–2.45], p<0.0001; I²=29%), and 5 years (OR 1.47 [1.08–2.00], p=0.010; I²=68%) following transplantation. Death-censored graft survival was lower with ABO incompatible kidney transplant than the control group at 1 year (OR 2.52 [1.80–3.54], p<0.0001; I²=61%) and 3 years (OR 1.59 [1.15–2.18], p=0.0040; I²=58%) only. Graft losses were equivalent to that of ABO compatible transplant recipients after 5 years and patient survival after 8 years. There is clear advantages for ABO compatible renal transplant compare to ABO incompatible renal transplant in the first 5 years following transplantation. Higher mortality were observe among ABO incompatible group due to risks of over immune suppression by intensified desensitization protocol and complicated with opportunistic infections. Besides, bleeding risks was higher among ABO incompatible group due to unselective plasmapheresis and immunoadsorption. In the first 5 years post ABO incompatible transplantation, risk of graft failure was high due to antibody mediated rejection and polyoma nephropathy especially HLA incompatible kidney recipients. However, long term data after 8 years revealed that no difference between both groups among the survivors. To overcome the negative outcome in ABO incompatible kidney transplant we need to refine and individualising the desensitising protocol and carefully select the maintenance immunosuppressive regimen for ABO incompatible kidney recipients. Limitations of this meta analysis include not assessing some of the important risk factors such as diabetes mellitus, cardiovascular disease and stability of graft function. Besides, variation of immunosuppressive protocol were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen. Furthermore, most of the observational studies were shorter than 5 years. On the other hand, this meta analysis involved large number of patients with high level of evidence in field of ABO incompatible renal transplant. In my opinion, we should carefully select potential candidate for ABO incompatible kidney transplants. We should explain in details regarding the risks and the long journey of immune desensitisation and immunosuppressant protocol. Early detection of complications and prompts action are crucial. Paired kidney exchange may serve as alternative for the deficiency of ABO incompatible kidney transplant. However, ethical issues and administrative barriers exist need to be taken into consideration.
summery
meta-analysis of 40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia>>>
The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-RTX in the first 5 years following organ implantation. Only long-term data after 8 years indicate the equal performance of the procedures for survivors
Graft losses were equivalent to that of ABOc-RTX after 5 years and patient survival after 8 years but the risks of post-operative complications, infections, and rejection were higher in ABOi-RTX so ABOi-RTX transplantations are still an option for ESRD patients but still inferior to ABOc. The alternate option to circumvent ABOi-RTX would be paired kidney exchange, which has been established in numerous centers
What is the level of evidence provided by this article?this study is a meta-analysis of observational studies >>> level of evidence 2a
strong points of this study??
· very large number of patients
· different races were included from different countries
The limitations??
o endpoints did not address all consented core outcome domains for studies of kidney transplantation.
o Only some items of the core outcome sets were encompassed in the primary studies and could be analyzed. Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient-reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
o Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitization regimen. Therefore, the effectiveness of the principal isoagglutinin removal technique, starting isoagglutinin thresholds, or the exposure to a specific combination of immunosuppressive drugs could not be assessed.
o The observational periods were shorter than 5 years in most studies and therefore fewer data were available for the analyses of clinical outcomes after 5 years.
o duplication for the same patient cohorts could not be ruled out.
o An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
also
o the results should not be considered conclusive due to the heterogeneity in the included study cohorts, with discordances in donor and recipient ages and immunological risk factors. Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
o the study did not cover ABOc-RTX from deceased donors or HLA-incompatible renal transplantation. A multipronged comparison of all four modalities (ABOi-RTX vs living ABOc-RTX vs deceased donor ABOc-RTX vs continued dialysis) in the context of a multicentre study or a network meta-analysis could help to further clarify the raised safety and efficacy issues.
Future questions need to be answered
· Further improvements in the immunological tests to combat blood group incompatibility-related complications can be achieved.
· A reduction in the dose of the immunosuppressive drugs applied could be beneficial
· how to use Pre-emptive antibiotics and virus-static therapy are also options to consider.
· how to monitor the coagulation system to decrease the risk of bleeding following plasmapheresis and immunoadsorption.
Summarise this article
The ABOi transplantation became an accepted option to overcome this shortage of both deceased & live donor pools. This systematic review and meta-analysis of observational studies assess the effect of ABOi transplantation on graft survival, patient survival at 1, 3, 5, and more than 8 years after transplantation ,infectious & non -infectious compared to ABOc transplantation.
Results and conclusion
ABOi when compared to ABO-compatible transplantation is associated with the following :
1-Higher risk of ABMR and mortality but not TCMR
2-Lower graft survival in the first 3 years post transplantation, but long term graft survival at 08 years is comparable to ABO compatible transplantation
4-Lower Death-censored graft survival at 1 and 3 years but not at 5 years post transplantation
5-Bleeding is the most common surgical complications related to ABO I transplantation due to removal of clotting factors by plasmapharesis.
6-There is an increase in the risk of infections and sepsis in ABOi when compared to compatible transplantation including pneumonia, UTI, wound infection, PCP, CMV and BK virus, which may be attributed to the use of rituximab.
7-Surgical revisions and lymphoceles are more frequently seen in ABOi transplantation due to unclear reason.
In short,efforts toward paired kidney donation programs should be maximized and combined with desensitization protocols to get more favourable outcomes.
What is the level of evidence provided by this article?
It is a systematic review and meta-analysis, level of evidence I
What are the weak and strong points of this study?
The strength of this study is its meta-analysis nature with level I of evidence and including very large pool of patients from different populations . ABOi-rTX may better than remaining on dialysis
Weakness arise from the lack of addressing other endpoints- no reports from the included studies about comorbid conditions like DM, cardiovascular disease, stability of graft function, different protocols used so increasing bias when interpreting the results, moreover most of the studies are of short term duration < 5 years, and clinical outcomes after 5 years cannot be analyzed. The exact time of complications( infections,surgical, and immunological) were not reported
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis
Kidney transplantation is the best renal replacement therapy, however, most patients remain long on a waiting list because of the scarcity of organs from deceased donors. ABO-incompatible kidney transplantation has been driven to overcome the problem of organ shortage by expanding the living donor pool. Pre-transplant desensitization strategies have been developed to overcome the isoagglutinin immunological barrier. This is done by plasmapheresis or immunoadsorption and the depletion of antibody-producing cells with rituximab. Many studies revealed no differences between ABO-incompatible transplantation and ABO-compatible transplantation, others; show conflicting results. Therefore, ABOi renal transplantation is still not universally adopted by all transplant centres.
Method:
This systemic review and meta-analysis were done according to the PROSPERO protocol. The authors followed the recommendations by the Cochrane Collaboration, the PRISMA statement, and the GRADE guidelines.
Paediatric and adult recipients of ABOi renal transplant, if an ABO-compatible control group was included and if data of outcomes of at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria were case reports, editorials, reviews, and letters, animal studies, meeting papers, studies with extractable data, non-renal solid organ transplant studies, and bone-marrow transplant studies. Also, non-English articles. All full texts of all trials that fulfilled the eligibility criteria were investigated.
Result and discussion:
The studies reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation. While long-term data after 8 years indicate the equal performance of both procedures for survivors. By the use of desensitization protocol with rituximab excess mortality with ABOi-rTx was only seen within the first 3 years, and death censored graft survival became similar to that of ABOc-rTx within the first year.
Paired kidney donation is one of the options to overcome the immunological barriers, although it is precluded by many countries by the law. Thus, ABOi-rTx remains the only option.
The study reveals that patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTx. This contributed to the over-suppressed immune system following desensitization causing high rate of infection such as CMV and polyoma nephropathy was higher in ABOi-rTx.
ABOi-rTx carries a higher incidence of bleeding, as a result of changes in the coagulation system. Lymphoceles are more common after ABOi-rTx.
The graft survival with ABOi-rTx was lower which is in line with a high risk of ABMR.
Rituximab-based desensitization protocols were clearly reducing the risk of humoral rejection, and the risk of ABMR in ABOi-rTx group was similar to that in the ABOc-rTx group 5 years after transplantation if rituximab was initially used.
Limitations: weak points
1- Not all consented core outcome domains did not address.
2- Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient-reported outcomes, could not be addressed.
3- Different immunosuppressive protocols and isoagglutinin thresholds were used between studies, so it is impossible to assess the effect of a specific induction and desensitization regimen.
4- The observational periods were short.
5- Heterogeneity in the included study was substantial, with discordances in donor and recipient ages and immunological risk factors.
6- Accurate report of the time after transplantation at which complications occurred was not stated.
7- Different patients characteristics.
strong points:
1- high level of evidence
2- a large number of patients
3- many countries
level of evidence:
Level 1- a meta-analysis
This article is a systematic review and meta-analysis of only observational studies up to 2017. Inclusion: All recipients of ABOi-KT were assessed if there was a control group of ABO compatible and at least one-year follow-up or more. Forty studies used for analysis among 1264 references that were published up to 2017. Cochrane, Embase, MEDLINE and PubMed were searched. Primary outcome were graft survival and mortality at 1, 3, 5 and more than 8 after TX. Secondary outcomes were infections and non-infections complications and rejections. Totally 40 studies were included for adult and pediatric recipients. ABOi-TX was associated with higher risk of 1,3 and 5 years mortality but not for 8-years or more mortality. At one and three years, death-censored graft survival was lower in ABOi-TX group comparing ABOC-TX group. More patients with sepsis, and surgical revision were included in ABOi-TX group. In addition, ABMR was more common in patients in ABOi-TX group. So, even with advanced protocols, patient mortality is higher in ABOi-TX due to over-immunosuppression or infections, especially if rituximab is used, although it decreased rate of ABMX.
The level of evidence provided by this article is 1.
Weak points: Not including outcomes such as cardiovascular diseases, stability of graft, diabetes, different desensitization and immunosuppression protocols. Not including isoagglutinin thresholds or removal technique, less data for outcome after 5 years.
Duplication bias can’t be ruled out. No RCTs
Strong points:
No bias regarding the outcome was seen. The level of evidence of this article is high and included large number of patients.
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis
Summarise this article
summary
This is a systematic review & meta-analysis of a large number of observational studies published up until Dec 31, 2017. It included a diversity of population of both adults & pediatrics.
The primary endpoints were all-cause mortality & graft survival at 1, 3, 5, & >8 years after transplantation.
ABO-i has a higher mortality at 1-, 3- & 5-year compared to ABO-c transplantation. The high mortality was related to the intense immunosuppression from desensitization treatments.
Graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants.
At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants.
The risk of infections & surgical complications was higher in ABO-i vs ABO-c
TCMR rates was not different between both groups, however the rate AMR was higher in ABO-i vs ABO-c transplants.
results
Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality 3 years and 5 years following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year and 3 years only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
discussion
This systematic review and meta-analysis is based on transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies involving more than 65000 patients . The analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation. Only long-term data after 8 years indicate equal performance of the procedures for survivors
even with the most advanced desensitisation protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX.
Type of study meta-analysis systemic review
Level 1
Summarise this article :
Introduction :
ABO-incompatible renal transplantation (ABOi-KT) is considered other option for patients on waiting list for long periods with no comptatible donors
This systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that compare data of 2 groups of ABOI-KT and ABOC-KT including 40 studies including 49 patient groups were identified.
65063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx.
Results :
At 1 , 3 and 5 year graft survival was lower after ABOi-KT than after ABOc-KT.
But at 8 years. Death-uncensored and death-censored graft survival weren’t lower after ABOi-KTthan after ABOc-KT.
-Sepsis was higher after ABOi-KTthan after ABOc-KT
-Surgical revision for hematoma, bleeding, and lymphocele was more in ABOI-KT than ABOc-KT.
-ABMR was higher in ABOi-KT than in ABOc-KT but No significant difference between ABOi-KT and ABOc-KT according to T-cell mediated rejection.
Using Rituximab in desensitization in ABO i making graft survival equal with ABO c KT
The risk of sepsis and cytomegalovirus infections was significantly higher in ABOi-KT patients that didn’t receive rituximab on desensitization protocol than in ABOc-KT.
No significant differences between ABOi-KT and ABOc-KT were found according to P jirovecii pneumonia and urinary tract infections, with any of the different desensitization protocols.
the risk of ABMR was significantly lower in ABOi-KT if Rituximab was used in desensitization protocols.
Discussion:
ABOc-KT was more beneficial with fewer hazards than ABOi-KT in the first 5 years of renal transplantation however they were equal on follow-up after 8 years.
The introduction of rituximab in desensitization protocols improves death-censored graft survival of ABOi-KT to be equal to ABOc-KT within the first year.
Patient mortality is higher in the first 5 years after ABOi-KT than after ABOc-KT.
What is the level of evidence provided by this article?
level 1 ( meta-analysis )
Strong points :
– Large numbers of the study sample
• Meta-analysis study with a high level of evidence
Weak Points :
· Cardiovascular risks and stability of graft functions were not studied.
· No specific protocol of desensitization or immunosuppression due to many different protocols were included in the studies used in meta-analysis
· Observational period was mostly 5 years with less information of outcome after 5 years.
· Accurate time of infectious and non-infection complications weren’t reported accurately.
· Differences in patients characteristics that may affect the outcome of KT, such as frailty status, duration of dialysis before transplantation, cardiovascular disease, and primary diseases, were not assessed in most of the studies
Summarise this article :
Introduction :
ABO-incompatible renal transplantation (ABOi-KT) is now indicated as another option for patients on the long waiting lists with no available compatible donor.
This systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that compare data of 2 groups of ABOI-KT and ABOC-KT including 40 studies including 49 patient groups were identified.
65063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx.
Results :
At 1-year graft survival was lower after ABOi-KTthan after ABOc-KT.
At 3 years graft survival was lower after ABOi-KTthan after ABOc-KT.
at 5 years. Death-uncensored, but not death-censored graft survival was lower after ABOi-KTthan after ABOc-KT
At 8 years. Death-uncensored and death-censored graft survival weren’t lower after ABOi-KTthan after ABOc-KT.
Sepsis was higher after ABOi-KTthan after ABOc-KT No statistically significant difference was observed in the risk of urinary tract infections, CMV.BK and P jirovecii pneumonia.
Surgical revision for hematoma, bleeding, and lymphocele was more in ABOI-KT than ABOc-KT.
ABMR was higher in ABOi-KT than in ABOc-KT.
No significant difference between ABOi-KT and ABOc-KT according to T-cell mediated rejection.
Death-censored graft survival at 1 year and 3years were equal in the ABOi-KT and the ABOc-KT if the desensitization program included Rituximab however was higher in ABOi-KT if Rituximab wasn’t used.
Death-censored graft survival at 5 years was equal in the ABOi-KT and the ABOc-KT if the desensitization program included Rituximab or not.
The risk of sepsis and cytomegalovirus infections was significantly higher in ABOi-KT patients that didn’t receive rituximab on desensitization protocol than in ABOc-KT.
No significant differences between ABOi-KT and ABOc-KT were found according to P jirovecii pneumonia and urinary tract infections, with any of the different desensitization protocols.
the risk of ABMR was significantly lower in ABOi-KT if Rituximab was used in desensitization protocols.
Discussion:
ABOc-KT was more beneficial with fewer hazards than ABOi-KT in the first 5 years of renal transplantation however they were equal on follow-up after 8 years.
The introduction of rituximab in desensitization protocols improves death-censored graft survival of ABOi-KT to be equal to ABOc-KT within the first year.
Patient mortality is higher in the first 5 years after ABOi-KT than after ABOc-KT.
level 1 ( meta-analysis )
Strong points :
Weak Points :
Kidney transplantation is the renal replacement therapy option with the greatest benefit for patients with end-stage renal disease . For this reason , many strategies developed to overcome organ shortage including transplantation against ABO incompatibility barrier.
In order to compare the outcomes between ABOi & ABOc Kidney Transplantation , a systematic review and meta-analysis of observational studies published up until Dec 31, 2017 , was conducted to compare ABOi-rTx in terms of graft survival, patient survival, and infectious and non-infectious complications to those of ABOc-rTx, and whether the effects were similar after taking different desensitisation strategies into consideration, such as the incorporation of rituximab based protocols.
Data analysis
Predefined primary outcomes were graft survival and all-cause mortality at 1, 3, 5, and more than 8 years .
after transplantation. Secondary outcomes were infectious and non-infectious complications, and graft rejections.
(Infectious complications included sepsis, urinary tract infections, cytomegalovirus infection, BK polyomavirus infection, and Pneumocystis jirovecii pneumonia. Non-infectious complications included surgical revisions, haematomas, lymphocoeles, and ureteral complications)
Results
After excluding incompete reports , 40 studies were included in the meta- analysis.
. as compared to ABOc KT :
1) MORTALITY. ABOi- rTx was associated with with a higher risk of 1-year mortality , 3-year mortality , 5-year mortality ), but not of 8-years or more mortality . However, subgroup analyses shows that 5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group
2 ) GRAFT SURVIVAL .At 1 year & 3 years :, death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx, as was death-uncensored graft survival . Althogh , Death-censored graft survival at 1 year was equal in the ABOi-rTx and the ABOc-rTx group, if the inital desensitisation protocol included rituximab . ( so it was worse in the non rtuximab group)
3) graft survival data after 5 years did not show significant differences between treatment groups when groups were analysed according to whether or not they received a rituximab desensitisation protocol
4) INFECTIONS. The risk of sepsis and cytomegalovirus infections after ABOi-rTx was significantly higher than after ABOc-rTx in patients who received non-rituximab-based desensitisation
protocols, but no difference was seen between treatment groups in those who received rituximab-based desensitisation protocols .
A higher risk for polyoma nephropathy was observed after ABOi-rTx than after ABOc-rTx in patients who received rituximab-based desensitisation
Regarding P jirovecii pneumonia and urinary tract infections, no significant differences between ABOi-rTx and ABOc-rTx were found with any of the initial desensitisation protocols
Additionally, the risk of serious infections and infectionrelated mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant
conditioning regimens
5)REJECTION.ABOi-rTx (rituximab or non rituximab group ) was not associated with significantly more overall rejections, borderline rejections, or T-cell mediated transplant rejections than was ABOc-rTx .
There was a trend for a higher risk of ABMR after AB0i-rTx than after AB0c-rTx with both desensitisation protocols .Nevertheless, the risk of ABMR was significantly lower if
an initial rituximab-based desensitisation protocol was used.
6)SURGICAL COMPLICATIONS .
Higher rates of bleeding events are reported after ABOirTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis .
Surgical revisions, with more postoperative wound infections, haematomas, and
lymphocoeles are more common after ABOi-rTx.
LEVEL OF EVIDENCE : level 1 ( meta-analysis )
Weak points in this study :
1) The endpoints did not address all consented core outcome domains for studies of kidney transplantation.
2) Other important domains, such as cardiovascular disease, stability of graft function or diabetes could not be addressed because studies included in the meta-analysis did not report them.
3)Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
4) The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years.
Strong points :
Being a meta-analysis study with high level of evidence and involving a large overall No. of patients .
This paper reviewed observational studies performed up to 2017,to compare ABOi with ABOc renal transplant outcome in term of patient and allograft survival. elaborating on infectious and non infectious complications reporting on all cause mortality and allograft survival.
features of this study:
1] 40 studies .
2] 65000 patients, with ABOi and ABOc transplantation.
3] All studies were systematically reviewed and were only observational conducted until the year 2017.
4 ]End points were all -cause mortality and and graft survival at 1,3, 5 and 8 years after transplantation.
Results:
1] it clearly showed statically significant benefit of ABOc over ABOi transplantation in term of all cause mortality and Allograft survival in the 1,3 and 5 years post transplant and they are equal after wards.
2]The high mortality rate in the first 5 years in the ABOi transplantation is obviously related to over immunosuppression and desensitization protocol.
3]The over immunosuppression predisposed to bacterial infection ,like sepsis and viral infection as CMV and BKV Nephropathy.
3] High rate of bleeding events in ABOi transplantation due to PP and IA.
4] Surgical complication, lymphocele and hematoma, surgical revision and wound infection.
5]Death censored graft survival was less in line with higher AMR in ABOi.
6]Polyoma nephropathy was more common in ABOi ,which might explain the lower graft survival in this group.
7] Early mortality post ABOi transplantation was shown to be less when the immunosuppression protocol modified to avoid Rituximab or to reduce the dose of MMF.
8]There is improvement in graft survival after 3 years post ABOi transplantation.
9] Risk of AMR is less 5 years after ABOi transplantation.
limitations and drawbacks
1]The general limitations related to meta analysis study.
2]Other important end points domains like cardiovascular disease, stability of allograft function ,DM, and meaningful patients reported outcomes were not addressed in this study.
3]The observational period was less than 5 years in most studies, therefore no information was available to assess long term outcome of study.
4]duplication of patients cohort.
5] Heterogeneity in the included study cohorts was substantial.
6]differences in patients characteristics ,that might affect the transplantation outcome were not reported.
points of strength in this study:
1] Involvement of large no. of patients.
2]Different countries.
3] Long term follow up period.
level of evidence is 1 as its a meta-analysis study.
Summary
It’s a systematic review and meta-analysis of observational studies published up until Dec 31, 2017 to investigate di!erences in outcome after ABOi-rTX and ABOc-rTX.
Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
A total of 1264 studies were screened and 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx. Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year , 3 years and 5 years mortality following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
Level of evidence
1.
What are the week and strong points of this study?
This study did not address all the core outcomes as endpoint supposed to be for studies of kidney transplantation e.g cardiovascular disease, and stability of graft function.
Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
outcome analysis after 5 yrs was not possible as Less data were available for the analyses of clinical outcomes after 5 years.
Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
. Differences in patients’ characteristics that might have an effect on transplantation outcomes was not reported in most of studies.
Strength of study
It was the most extensive synthesis of available evidence assessing clinical outcomes of ABOi-rTx in comparison with ABOc-rTx.
Summarise this article
*This systematic review and meta-analysis
Level of evidence is 1.
*ABOI-KT was considered a contraindication indication in the past but it started to be widely accepted in many centres due to shortage of donors and long waiting time on dialysis.
Recent advances in immunosuppssion and desensitization protocols allowed more ABOI-RTX.
*This is a systemic review of transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies including 49 patient groups and more than 65000 patients of which 7098 had ABOi-Tx.
aiming to investigate differences in outcome.
*Results
-There was a clear benefit of ABOc-Tx over ABOi-Tx in 5 years after implantation.
– longer follow up for 8 years both groups showed the same survival rates .
– Inclusion of rituximab therapy decreased the risk of ABMR within 5 years after transplantation also
desensitisation with rituximab improved survival and death-censored graft survival after 1 year to be equal to recipients of ABOc-rTx
But still the risk of ABMR
higher after ABOi-rTx than after ABOc-rTX.
-patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX.
infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus) was the main cause of death
– other common complications includes hemorrhage, Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles.
-avoidance of aggressive initial immunosuppressive protocols and individualising the immunosuppressive therapy reduced the higher early mortality.
*What are the weak and strong points of this study?
•Strength points
-Systemic review with high level of evidence
-Large number of studies were reviewed with large number of patients.
-showed good results of adding rituximab to induction and good resullts avoiding aggressive immunosuppression.
•Limitations:
-endpoints did not address all consented core outcome domains for studies of kidney transplantation.
– didn’t addresse other complications as CVD, stability of graft function, diabetes, or meaningful patient-reported outcomes.
-Different immunosuppressive protocols were used between studies.
-The observational periods were shorter than 5 years in most studies and less data were available for the analyses of clinical outcomes after 5 years.
– inclusion criteria of patients in the studies were not uniform .
-didn’t cover ABOc-rTx from deceased donors.
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis:
Aim:
To investigate differences in outcome after ABOi-rTX and ABOc-rTX.
Introduction:
Removal of is isoagglutinins by plasmapheresis or Immunoadsorption and the depletion
of antibody producing cells with rituximab, have enabled ABO incompatible renal
transplantation (ABOi-rTx).
Methods:
A systematic review and meta-analysis of observational studies.
Search strategy and selection criteria this systematic review and meta-analysis.
Data analysis Predefined primary outcomes were graft survival and all-cause mortality at
1, 3, 5, and more than 8 years.
Secondary outcomes were infectious and non-infectious complications, and graft
rejections. Infectious complication.
Result:
Mortality risk:
Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year
mortality, 3 years and 5years posttransplant. Death-censored graft survival was lower
with ABOi-rTx than with ABOc-rTx at 1 year and 3yearsbut not at 8years.
Rituximab-based versus no rituximab-based desensitation protocols revealed higher 1-
year and 3-year mortality after ABOi-rTx than after ABOc-rTx regardless of the initial
desensitisation protocol.
5 years after transplantation, ABOi-rTx was not associated with significantly higher
mortality than was ABOc-rTx in the rituximab group, compared with the group without
rituximab.
Graft losses:
Were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
At 1 and 3 year, death-censored graft survival was lower after ABOi-rTx than after ABOc-
rTx , as was death-uncensored graft survival.
At 5years, Death-uncensored but not death-censored graft survival was lower after
ABOi-rTx than after ABOc-rTx.
At 8 years or more Death-censored and death-uncensored graft survival were not lower
after ABOi-rTx than after ABOc-rTx.
Infection risk:
Sepsis was higher after ABOi-rTx than after ABOc-rTx .
No statistically significant difference was observed in the risk of urinary tract infections,
cytomegalovirus infection, BK polyomavirus infection, and P jirovecii pneumonia.
Surgical complication risk:
A greater proportion of patients who had ABOi-rTx had surgical revision than those who
had ABOc-rTX (, bleeding or hematomas, and lymphoceles.
No significant difference in the proportion of patients with surgically treated
lymphoceles or ureteral complications, between patients who had ABOi-rTx and those
who had who had ABOc-rTx.
Rejection Risk:
No significant difference between treatment groups was observed in overall, borderline,
or T-cell mediated rejections.
By contrast, the proportion of patients with ABMR was higher after ABOi rTX than after
ABOc-rTx .
Discussion:
The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5
years following organ implantation.
Only long-term data after 8 years indicate equal performance of the procedures for
survivors.
Excess mortality with ABOi-rTx was only seen within the first 3 years, and death-
censored graft survival became similar to that of ABOc-rTx within the first year.
Refining the initial immunosuppressive protocols may reduce risk of infection, bleeding
and surgical complication.
level of evidence 1.
Weak points:
Not include all consented core outcome domains for studies of kidney transplantation.
Other important domains, such as cardiovascular disease, stability of graft function,
diabetes, or meaningful patient reported outcomes, could not be addressed.
Different immunosuppressive protocols were used between studies, making it impossible
to assess the effect of a specific induction and desensitisation regimen.
The observational periods were shorter than 5 years in most studies and therefore less
data were available for the analyses of clinical outcomes after 5 years.
Differences in patients’ characteristics.
Discordances in donor and recipient ages and immunological risk factors.
strong points :
metanalysis study .
Large number of patient.
High level of evidence.
The aim of the study;
was to investigate differences in outcome after ABOi-Tx and ABOc-Tx
The type of the study;
This systematic review and meta-analysis.
Population;
More than 65 000 patients originated from the USA, Europe, Asia, and Australia. 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-Tx.
Conclusions
Compared with ABOc-Tx, ABOi-Tx was associated with significantly higher 1-year mortality 3 years and 5 years following transplantation. Death-censored graft survival was lower with ABOi-Tx than with ABOc-Tx at 1 year and 3 years only. Graft losses were equivalent to that of ABOc-Tx after 5 years and patient survival after 8 years.
What is the level of evidence provided by this article?
Level 1
What are the weak and strong points of this study?
This is a systematic review and meta-analysis with a level of evidence: I
This paper reviewed studies of ABO-incompatible transplantations till December 2017 compared to compatible ones. subgroup analyses included analysis of death censored and non-censored graft survival, sepsis, surgical revision, and rituximab based desensitization.
compare with ABO compatible Tx, ABOi-RT was associated with higher mortality in the first and 3rd years but equal after 8th year.
In 36 studies (59970 patients) death censored survival at one year was lower in the BO compatible group
Rituximab based desensitization protocols had higher mortality in the AO incompatible group both at 1st and 3rd years post-transplantation.. especially in the first 5 years the survival was higher with ABO compatibility compared to ABOi Tx. immune suppression and related infection seem to play a role in lower graft survival in ABOi transplants.
when we decide to transplant against ABO incompatibility, evaluation is beneficial to compare in relation ABO compatibility, deceased donor transplant, on and remaining on dialysis. Kidney paired donation should be considered as well
Summary:
Systematic review and meta-analysis assessing the best evidence available from the review of observational studies with > 1 year follow up. tin his review they compare the clinical outcome of ABOi TX with control group of ABOc KTX, about 1265references available for analysis and around 40 studies included from 1998- till 2017 by reviewing all the studies published in Cochrane(CENTRAL) , PubMed, embase , Midline
They exclude all case reports or editorial comments , letters, in adequate data or follow up < 1 year, animal studies, non-renal solid organ transplant, and non-English articles, they included 65000 of patients and about 7000 patients underwent ABOi KTX compared with ABOc living donor KTX as control group .the primary endpoint of 1,3 and 5 years graft survival , 8 Years mortality as secondary endpoint outcome.
Results:
ABOi-KTX associated with higher rate of infection in the first-year post TX, more surgical complication hematoma, bleeding lymphocele
The graft and patient survival were found lower in ABOI ktx in the first three years which can be explained by higher rate of infection and rejection, while 5 years clinical graft outcome were similar in the two group .and this review highlight the inferiority effect of ABOI ktx by all the points.
early higher mortality rate correlated to the intense immunosuppression including high dose rituximab with associated high risk of serious infections like CMV ,polyoma Viral infection , bacterial infection ,subgroup analysis from some studies reported better outcome and graft survival with desensitization protocols using low dose rituximab or rituximab free regimens
Death (censored and uncensored) graft survival was lower in ABOi KTX at one year,3 Years respectively , and its associated with higher ABMR rate while at 8 years the death censored and uncesord was not lower in ABOi tx compared to ABOcTX .
Using rituximab based desensitization protocol associated with lower rate of ABMR and more infections including sepsis , cmv ,BKV ,pjp
Over all the ABOi TX still associated with favorable outcome in highly sensitized patients compared to long waiting list on dialysis .according to the results from this review we should expand and encourage the use of paired kidney exchange program and limit the use of ABOI tx with tailored immunosuppression protocol for those whom failed to be included in PKD program .
Strength of the study
1-High level of evidence
2- using different statistical data analysis including sequential analysis to avoid bias
3-No publication bias correlated to graft survival as outcome.
Limitation of the study:
1- No RCT in this systematic review and meta-analysis
2- Not all outcome points are answered some domains that could affect the outcome other than infection and rejection not assessed like frailty score , cardiovascular disease, DM
3- heterogenicity of the patients characteristics might affect the outcome.
4- different immunosuppression and desensitization protocols
5- 5 years follow-up consider short observational period to address solid outcome .
Level of evidence : 1B( no single RCT , all from observational studies with heterogenicity in patients selections criteria and desensitization protocols )
Introduction
The ABO blood group barrier has long been considered a contraindication to renal transplantation due to increased risk for humoral rejection and early graft loss. Now, this barrier is being crossed after the development of pretransplant desensitization strategies.
Methods
Search strategy and selection criteria
Systematic review and meta-analysis
Results
Compared with ABOc-rTX, ABOi-rTx was associated with a higher risk of 1-year mortality, 3-year mortality, 5-year mortality, but not of 8-years or more mortality.
At 1 year, death-censored graft survival was lower after ABOi-rTx than after ABOc-rTX.
At 3 years, death-censored and death-uncensored graft survival was lower after ABOi-rTx than after ABOc-rTX.
The proportion of patients with sepsis was higher after ABOi-rTx than after ABOc-rTX.
No statistically significant difference was observed in the risk of urinary tract infections, cytomegalovirus infection, BK polyomavirus infection, and P jirovecii pneumonia.
A greater proportion of patients who had ABOi-rTx had surgical revision than those who had ABOc-rTX, bleeding or hematomas, and lymphocele.
The proportion of patients with ABMR was higher after ABOirTx than after ABOc-rTX.
Subgroup analyses of rituximab-based versus nonrituximab-based desensitization protocols revealed higher1-year and 3-year mortality after ABOi-rTx than after ABOc-rTX regardless of the initial desensitization protocol.
5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTX in the Rituximab group.
Death-censored graft survival at 1 year was equal in the ABOi-rTx and the ABOc-rTX group, if the initial desensitization protocol included rituximab.
Death-censored graft survival at 3 years was worse in the ABOi-rTx group given nonrituximab-based desensitization protocols than in the ABOc-rTX group.
The risk of sepsis and cytomegalovirus infections after ABOi-rTx was significantly higher than after ABOc-rTX in patients who received non-rituximab-based desensitization protocols.
A trend for higher risk for Polyoma nephropathy was observed after ABOi-rTx than after ABOc-rTX in patients who received rituximab-based desensitization protocols.
Regarding P jirovecii pneumonia and urinary tract infections, no significant differences between ABOi-rTx and ABOc-rTX were found with any of the initial desensitization protocols.
The risk of ABMR was significantly lower if an initial rituximab-based desensitization protocol was used.
level of evidence :1
weak points:
No RCT (randomized controlled trial) was included in the review.
No standard protocol was used in the different studies.
strong points:
large size of population.
high level of evidence.
· A systematic review and meta-analysis of multiple observational studies from different populations of different age groups..
OUTCOMES following ABOI-KT
Mortality rate in the patients transplanted from ABOI donor is higher at 1, 3 and 5 years post-transplant in comparison with recipients with ABO compatible donor, and become similar at 8 years post transplantation; mostly attributed to side effects of aggressive immunosuppression like infections either bacterial and viral like BK virus, CMV, and coagulation disorders.
Incidence of AMR is higher in the patient with ABO incompatible compared to those with ABO compatible donor in spite of aggressive immunosuppression and use of rituximab.
level of evidence 1(Systematic review with meta analysis)
Strong points include involvement of large number of studies from different areas allow good scope of the patients and results.
Weak points include lacking of randomized clinical trials, some endpoints not mentioned in studies like cardiovascular risk, graft function stability, also use of different protocols of immunosuppression not allowing possible comparison to get real assessment , and follow up 5 years.
.-The ABO blood group barrier has long been considered a contraindication to renal transplantation because of the increased risk for humoral rejection and early graft loss.
-Pretransplant desensitization strategies, such as the removal of isoagglutinins by plasmapheresis or immunoadsorption and the depletion of antibody-producing
cells with rituximab, have enabled ABOincompatible renal transplantation (ABOi-rTx).
-It systematic review and meta-analysis were done according to the PROSPERO protocol.
-It is based on transplantation data (patient and graft survival) for ABOc-rTX and ABOi-rTx from 40 studies involving more than 65 000 patients originating from the USA, Europe, Asia, and Australia.
-The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation. Only long-term data after 8 years indicate the equal performance of the procedures for survivors.
-With the introduction of a desensitization strategy that includes rituximab excess mortality with ABOi-rTx was only seen within the first 3 years, and death-censored graft survival became similar to that of ABOc-rTx within the first year.
-The advent of ABOi-rTx provides novel options for patients in need of a transplanted organ with a living donor.
-Patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX. -This higher mortality could be a result of side effects due to an over suppressed
immune system following desensitization with the emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus).
-Higher rates of bleeding events are reported after ABOirTx than after ABOc-rTX, probably due to changes in the coagulation system following plasmapheresis or high volume plasma exchange, or both.
-Surgical revisions, with more postoperative wound infections, hematomas, and
lymphoceles are more common after ABOi-rTx.
-The risk of postoperative bleeding appears to be especially high if immunoadsorption is used.
-Cytomegalovirus prophylaxis protocols might explain the reduced proportion of patients with early cytomegalovirus infections at present, which obviates viral infections regardless of the cytomegalovirus risk status.
-The risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant conditioning regimens, or other immunosuppressive agents, in the course of the induction therapy.
-The higher early mortality after ABOi-rTx than after ABOc-rTX could be overcome by refining the initial immunosuppressive protocols and individualizing the immunosuppressive therapy.
– In smaller studies, selected patients receiving either a reduced dose of rituximab, no rituximab, or no plasmapheresis during the induction phase, or
lower doses of mycophenolate mofetil during the maintenance phase after ABOi-rTx showed exceptionally good outcomes with less infectious complications and
without increased incidence of acute rejection.
– The lower graft survival with ABOi-rTx was in line with a high risk of ABMR. Inclusion of rituximab therapy decreased the risk of ABMR 5 years after transplantation.
-Polyoma nephropathy was more common after ABOi-rTx than after ABOc-rTX in patients who received rituximab based desensitisation protocols.
-The risk of developing polyoma virus-associated nephropathy in patients who have undergone ABOi-rTx is even significantly higher than in recipients of HLA-incompatible kidney transplants.
-Patients undergoing ABOi-rTx are at higher immunological risk because of a
re-transplant condition, older age, unrelated donors, more HLA mismatches, or higher panel reactive and donorspecific antibody amounts, than are those undergoing ABOc-rTX.
– Rituximab isnot efficient in reducing the concentration of preformed DSA or preventing the development of de-novo DSA, both well known and strong risk factors for chronic ABMR and poor graft outcomes.
Limitations of this study:
– Endpoints did not address all consented core outcome domains for studies of kidney transplantation. Only some items of the core outcome sets were encompassed in the primary studies and could be analyzed. Other
important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient-reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
-Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitization regimen.
-The observational periods were shorter than 5 years in most studies and
therefore fewer data were available for the analyses of clinical outcomes after 5 years.
–the strong point,it is meta analysis study involved large number of studies from different centres .
Level of evidence: 1
INTRODUTION
The ABO blood group barrier has long been considered a contraindication to renal transplantation because of the increased risk for humoral rejection and early graft loss. However, pretransplant desensitisation strategies, such as the removal of isoagglutinins by plasmapheresis or immunoadsorption and the depletion of antibody producing cells with rituximab, have enabled ABO-incompatible renal transplantation (ABOi-rTx).
Although smaller studies evaluating patient and graft outcome after ABOi-rTx did not show any striking differences compared with living donor ABO-compatible renal transplantation (ABOc-rTx), larger registry data have showed conflicting results.
METHODS
This systematic review and meta-analysis was done according to the PROSPERO protocol, followed the recommendations by the Cochrane Collaboration, the PRISMA statement and the GRADE guidelines.
Were analysed studies of paediatric or adult recipients of ABOi-rTx, if an ABO-compatible control group was included and if outcome data for at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria were case reports, editorials, reviews and letters, animal studies, meeting papers, studies with unextractable data, non-renal solid organ transplant studies, and bone-marrow transplant studies. Non-English articles were excluded.
The following keywords were used, with the use of wildcard characters to account for variations in spelling and plurals: “ABO” OR “AB0” in combination with “incompatible” AND “renal” OR “kidney”; “ABOi” OR “AB0i” in combination with “renal” OR “kidney”. No other search restrictions were Applied.
DATA ANALYSIS
Data analysis Predefined primary outcomes were graft survival and all-cause mortality at 1, 3, 5, and more than 8 years after transplantation. Secondary outcomes were infectious and non-infectious complications, and graft rejections.
Because of the absence of randomised controlled studies identified in the search, the risk of bias was assessed by the use of the Newcastle-Ottawa Scale and included the following items: representativeness of the exposed population, appropriate election and comparison of the study groups, adequate ascertainment of exposure (preconditioning therapies), and accuracy of outcome assessment.
We calculated the summary estimates using Review Manager (RevMan, version 5.3) and trial sequential analysis program version 0.9 beta.15 We used a p value of 0∙033. Because cumulative meta-analyses are at risk of producing random errors due to sparse data and multiple testing of accumulating data, we used trial sequential analysis to assess this risk.
RESULTS
Compared with ABOc-rTX, ABOi-rTx was associated with a higher risk of 1-year mortality (D²=65%), 3-year mortality (D²=58%), 5-year mortality (D²=83%), but not of 8-years or more mortality (D²=0%).
The proportion of patients with sepsis was higher after ABOi-rTx than after ABOc-rTx (D²=0%). No statistically significant difference was observed in the risk of urinary tract infections (D²=48%), cytomegalovirus infection (D²=71%), BK polyomavirus infection (D²), and P jirovecii pneumonia (D²=0%).
A greater proportion of patients who had ABOi-rTx had surgical revision than those who had ABOc-rTX (D²=0%), bleeding or haematomas (D²=2%), and lymphocoeles (D²=82%). We found no significant difference in the proportion of patients with surgically treated lymphocoeles (D²=61%) or ureteral complications (D²=0%) between patients who had ABOi-rTx and those who had who had ABOc-rTx.
No significant difference between treatment groups was observed in overall (D²=69%), borderline (D²=74%), or T-cell mediated rejections (D²=0%). By contrast, the proportion of patients with ABMR was higher after ABOi-rTx than after ABOc-rTx (D²=51%).
Subgroup analyses of rituximab-based versus non-rituximab-based desensitation protocols revealed higher 1-year and 3-year mortality after ABOi-rTx than after ABOc-rTx regardless of the initial desensitisation protocol without rituximab. 5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group compared with the group without rituximab.
Death-censored graft survival at 1 year was equal in the ABOi-rTx and the ABOc-rTx group, if the inital desensitisation protocol included rituximab and was worse in the ABOi-rTx group than the ABOc-rTx if the inital desensitisation protocol did not include rituximab. Death-censored graft survival at 3 years was worse in the ABOi-rTx group given non-rituximab-based desensitisation protocols than in the ABOc-rTx group but was similar to the ABOc-rTX group in those who received rituximab-based desensitisation protocols. Studies reporting graft survival data after 5 years did not show significant differences between treatment groups when groups were analysed according to whether or not they received a rituximab desensitisation protocol.
The risk of sepsis and cytomegalovirus infections after ABOi-rTx was significantly higher than after ABOc-rTx in patients who received non-rituximab-based desensitisation protocols, but no difference was seen between treatment groups in those who received rituximab-based desensitisation protocols.
The risk for polyoma nephropathy was not lower after ABOi-rTx than after ABOc-rTx in patients who received non-rituximab-based desensitisation protocols, but there were only two studies reporting such data.
Regarding P jirovecii pneumonia and urinary tract infections, no significant differences between ABOi-rTx and ABOc-rTx were found with any of the initial desensitisation protocols.
In patients who received either rituximab or non-rituximab-based desensitisation protocols, ABOi-rTx was not associated with significantly more overall rejections, borderline rejections, or T-cell mediated transplant rejections than was ABOc-rTx. Nevertheless, the risk of ABMR was significantly lower if an initial rituximab-based desensitisation protocol was used.
DISCUSSION
The meta-analysis clearly shows that even with the most advanced desensitisation protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX. This higher mortality could be a result of side-effects due to an over-suppressed immune system following desensitisation with emergence of life-threatening infections of bacterial (sepsis) and viral origin (eg, cytomegalovirus).
Higher rates of bleeding events are reported after ABOi-rTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis or high volume plasma exchange, or both. Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles are more common after ABOi-rTx.
Cytomegalovirus prophylaxis protocols might explain the reduced proportion of patients with early cytomegalovirus infections at present, which obviates viral infections regardless of the cytomegalovirus risk status.
Additionally, the risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant conditioning regimens, or other immunosuppressive agents, in the course of the induction therapy.
The lower (death-censored) graft survival with ABOi-rTx was in line with a high risk of ABMR. Inclusion of rituximab therapy decreased the risk of ABMR 5 years after transplantation; however, the OR for ABMR was still in the group that had not received rituximab. Polyoma nephropathy was more common after ABOi-rTx than after ABOc-rTX in patients who received rituximab-based desensitisation protocols, which could be explained by viral escape from the immune surveillance. Polyoma nephropathy is probably another reason for the lower graft survival after ABOi-rTx, although we did not find a statistically significant difference in the analysis.
This is a secondary study – with systematic review and meta-analysis. Level evidence – 01.
– Week : risk of bias
– Strong: Allows generalizing data
summarize the contents of this article
Renal transplantation for patients with ABO incompatibility is becoming more popular as a means of addressing organ shortages. Evidence of its non-inferiority in contrast to ABO-compatible kidney transplantation must be evaluated at both the early and late stages of the disease process, the researchers say.
An observational study with outcome data (at least one year after ABOi-Tx) and an ABO-compatible control group was included in this systematic review and meta-analysis, which was published on December 31, 2017.
Methods: In order to be included, trials on recipients of ABOi-Tx had to include an ABO-compatible control group, as well as outcome data on at least graft or recipient survival with at least one year of follow-up available.
Case reports, editorials, reviews, and letters were all excluded, as were animal studies, meeting papers, studies that we’re unable to extract data, non-renal solid organ and bone-marrow transplant studies, and dead donor ABOc-Tx. Case reports, editorials, reviews, and letters were all excluded.
The information in this study was derived from previously published papers.
At 1, 3, 5, and more than 8 years following transplantation, the primary outcomes were all-cause death and graft survival, respectively.
Finding: ABOi KT treated with rituximab against ABOc KT: At the first and third years, mortality rose but remained stable after that. Survival of filtered grafts is comparable to death.
At 1 and 3 years, the risk of AMR is higher, but at 5 years, the risk is the same. ABOi KT with or without rituximab against ABOc KT:
At the ages of 1, 3, and 5 years, mortality rose, and the trend remained similar at the age of 8. Graft survival was decreased at 1, 3, and 5 years after transplantation when death was filtered out.
An increased risk of CMV and sepsis, with an equal incidence of Polyoma nephropathy, urinary tract infections, and pneumocystis infections.
Level of evidence: Level 1
-a few elements from the main outcome sets were included in the original investigations and were thus able to be examined.
There were no studies included in the meta-analysis that reported on other critical categories such as cardiovascular disease, graft function stability over time, diabetes, or relevant patient-reported outcomes.
-The research cohorts included in this analysis were very heterogeneous, with significant differences in donor and recipient ages as well as immunological risk factors.
-The majority of the studies did not describe differences in patient variables that can have an impact on transplantation outcomes, such as frailty status, length of dialysis before transplantation, cardiovascular disease load, and primary illnesses.
Strong point: high level of evidence and a large number of studies and a variety of populations.
· Summary:
· This is a systematic review & meta-analysis of many observational studies from different populations of adults & pediatrics.
· The primary outcome is all-cause mortality & graft survival at 1, 3, 5, >8 years after transplantation.
· ABO-i transplantation has higher mortality at 1, 3, 5 year post transplant which can be attributed to intense immunosuppression from desensitization treatments. However, graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants.
· At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants.
· The risk of infections & surgical complications was higher in ABO-i vs ABO-c.
· TCMR rates was not different between both groups, however the rate of AMR was higher in ABO-i vs ABO-c transplants.
· It is last option in case of failure of PKD to get compatible donor.
· Q2 . level of evidence: Level I
· Q3. Week points:
· The incidence of many complications as cardiovascular disease, stability of graft function & diabetes were not addressed.
· it depends on observational studies, no randomized controlled trials.
· No comparison as regard different immunosuppressive regimen used.
· Strong points:
· No publication bias regarding the mortality outcome.
· The meta-analysis was conclusive regarding the mortality at 1 year, 5 years.
Summary of this article-
1.ABOi tx is a/w higher 1yr,3yr,5yr mortality but not 8yr mortality as compared to ABOc tx.(due to overimmunesuppression- infections)
2.Death censored and uncensored graft survival is lower in ABOi tx than ABOc tx at 1yr,3yr,but only death uncensored graft survival at 5yr is lower not death censored with no change of graft survival at 8yr between ABOc and ABOi tx.(mainly due to ABMR,polyoma nephropathy)
3.Though sepsis is more common in ABOi tx than ABOc tx but no difference in incidences of uti,pcp,bkv and cmv infections in between the two groups even though this difference even not exist between two grps whether recieved rtx or not in ABOi tx.(though bit of contradictory but cannot be ascertained on the basis of varied populations and in some studies rtx is more a/w with bkv nephropathy)
4.Greater no of surgical complication (hematoma,lymphocele…)occurs in ABOi tx than ABOc tx.(due to loss of coagulation protein in plasma exchange)
5.More no of ABMR occurs in ABOi tx than ABOc tx with simmilar incidence of TCMR in both the groups with more abmr in non rituximab group than rituximab group in ABOi tx.(due to ABO ag barrier)
6.whether rituximab given or not will not change the fate of patient and graft after 5yrs,but death censored graft survival is lesser at 1yr,3yr in ABOi tx group who were not recieved rituximab than who recieved rituximab.(due to less ABMR)
LEVEL OF EVIDENCE IS 1
LIMITATION OF THIS STUDY
A.not a rct
B.different immunesuppressive protocol
C.other domain like CVS,DM,graft outcome not addressed
D.used allmost observational studies
E.different method used for ab titre, ab removal
F.observational period is shorter than 5yrs in many studies, so very grey zone to comment above 5yrs outcome.
STRONG POINTS
A.varied population group included
B.high level of evidence.
SO CONCLUDING that ABOi tx will decrease the waiting time with increases the organ pool, but infection still a alarming point which require lesser immune suppression with rejection ,which still needs kidney paired donation before ABOi tx.
ABOi vs ABOc
ABOi KT were associated with lower patient survival at 1,3 and 5 years while comparable to ABOc KT after 8 years post-transplant. ABOi that were not given rituximab had lower patient survival at 5 years than those with ABOc KT. The increased mortality is due to intensive immunosuppression causing increased infections and sepsis, especially with high dose rituximab. ABOi KT was associated with lower death censored and death uncensored graft survival at 1- and 3-years post-transplant while death censored graft survival was comparable to ABOc KT after 5 years and death uncensored graft survival was like ABOc KT after 8 years. Lower graft survival is due to increased AMR and polyoma nephropathy. ABOi KT had increased incidence of sepsis, but similar rates of UTI, CMV, BK virus and Pneumocystis jirovecii pneumonia. ABOi KTwere associated with increased surgical revisions, although there was no difference in bleeding or hematoma, lymphocele, or ureteral complications. There was increased risk of AMR in ABOi group, although the rates of overall rejections, T cell mediated rejections and borderline rejections were similar.
ABOi KT using rituximab VS ABOc KT:
· Mortality increased at 1 and 3 years, but similar after that
· Death censored graft survival similar
· Increased risk of Polyoma nephropathy, but similar risk of CMV, sepsis, UTI and pneumocystis infections
· Increased risk of AMR at 1 and 3, but similar at 5 years
ABOi KT w/out rituximab VS ABOc KT:
· Mortality increased at 1, 3 and 5 years, similar after 8 years.
· Death censored graft survival lower at 1,3- and 5-years post-transplant.
· Increased risk of CMV and sepsis with similar rates of Polyoma nephropathy, UTI and pneumocystis infections
· Significantly Increased risk of AMR.
Level 1 evidences
Strong points
large number of studies from different aspects to allow diversity of the patients and results.
Weak points
lack of RCTs
endpoints not measured- cardiovascular risk, DM, graft function stability
Various protocols of immunosuppression
study follow up was 5 years only
ABO-incompatible renal transplantation is increasingly used to overcome organ shortages. Evidence about its non-inferiority in comparison with ABO-compatible renal transplantation needs to be analysed at early and late time points.
Methods: a systematic review and meta-analysis of observational studies published till Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-Tx and included an ABO-compatible control group.
Searching Methods:
Trials on recipients of ABOi-Tx were assessed if an ABO-compatible control group was included and if outcome data on at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-Tx.
Data were extracted from published reports.
Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
Data analysis:
1264 studies were screened.
1121 studies were excluded
143 abstracts reviewed
90 articles excluded
51 full-text articles reviewed
16 articles excluded
40 studies including 49 patient groups were identified.
65063 patients were eligible for analysis, 7098 of whom had undergone ABOi-Tx.
The risk of bias was assessed by the use of the Newcastle-Ottawa Scale because of the absence of RCTs.
The summary estimate was calculated using Review Manager version 5.3.
The statistical heterogeneity was identified by forest plots.
Findings:
Compared with ABOc-Tx, ABOi-Tx was associated with significantly higher 1-year, 3 years and 5 years mortality.
Death-censored graft survival was lower with ABOi-Tx than with ABOc-Tx at 1 year and 3 years only.
Graft losses were equivalent to that of ABOc-Tx after 5 years and patient survival after 8 years.
No publication bias was detected
There was statistical heterogeneity
Interpretation:
Despite progress in desensitisation protocols and optimisation of ABOi-Tx procedures, excess mortality and loss of kidney grafts were found compared with ABOc-Tx within the first 3 years after transplantation.
Only long-term outcomes after 5 years yielded equivalent survival rates and organ function.
Awareness of the increased risks of infection, organ rejection, and bleeding could improve the care of patients and promote efforts toward paired kidney exchange programmes.
Level I
Limitations:
Strong points:
This article is systemic review and meta analysis study involving 40 studies and large number of population more than 65000 patients to investigate differences between ABOI and ABOc renal transplant in base of graft survival, patients survival and infectious and non infectious complications related to ABOI.
This article shows increase incidence of ABMR in those with ABOI who not receive rituximab as part of desensitisation protocol and worse graft survival in those patients in comparison to ABOc rt. also decrease patients survival in ABOI because high incidence of sepsis due to intensified immunosuppressive drug, However no significant difference in related to urinary tract infection and CMV or BK polyomavirus.
Also shows increase incidence of bleeding and hematoma due to plasma pharesis and immunoadsorption in patients with ABOI renal transplant and there’s increase risk of lumphocele and infected wounds in dose patients with ABOI renal transplant.
PKD better than desensitisation protocol in ABOI.
This article evidence 1
weak point / This article is observation study
it’s not randomised control trials
system review less than 5 years
No assessed age of patients/ primary disease/ time of waiting list and long time staying on dialysis / cardiovascular disease and diabetes.
Not assessed different desensitisation protocol
strong point large size of population
address survival of graft and patients survival and complications in ABOI in comparison to ABOc
· Summarise this article
ABO incompatible transplantation has increased transplant numbers and reduced waiting times for a kidney transplant. This systematic review was done to analyse the graft outcomes in ABO incompatible transplants vis-à-vis ABO compatible transplants.
The review included 40 studies with more than 65000 patients out of which more than 7000 patients underwent ABO incompatible transplant. Patient and graft survival at 1, 3 , 5 and more than 8 years was assessed.
ABO incompatible transplants were associated with lower patient survival at 1,3 and 5 years while patient survival was similar to ABO compatible transplants at more than 8 years post-transplant. Patients who were not given rituximab had lower patient survival at 5 year than those with ABO compatible transplants. The increased mortality is due to intensive immunosuppression causing increased infections and sepsis, especially with high dose rituximab.
ABO incompatible transplant was associated with lower death censored and death uncensored graft survival at 1 and 3 years post-transplant while death censored graft survival was similar to ABO compatible transplants after 5 years and death uncensored graft survival was similar to ABO compatible group after 8 years. Lower graft survival is due to increased AMR and polyoma nephropathy.
ABO incompatible transplants had increased incidence of sepsis, but similar rates of UTI, CMV, BK virus and Pneumocystis jirovecii pneumonia. ABO incompatible transplants were associated with increased surgical revisions, although there was no difference with respect to bleeding or hematoma, lymphocele or ureteral complications.
There was increased risk of AMR in ABO incompatible group, although the rates of overall rejections, T cell mediated rejections and borderline rejections were similar.
Comparing ABO incompatible transplants using rituximab with ABO compatible transplants:
1) Mortality increased at 1 and 3 years, similar later
2) Death censored graft survival similar
3) Increased risk of Polyoma nephropathy, but similar risk of CMV, sepsis, UTI and pneumocystis infections
4) Increased risk of AMR at 1 and 3 , but similar at 5 year
Comparing ABO incompatible transplants without using rituximab with ABO compatible transplants:
1) Mortality increased at 1, 3 and 5 years, similar after 8 years.
2) Death censored graft survival lower at 1,3 and 5 years post trasnplant.
3) Increased risk of CMV and sepsis with similar rates of Polyoma nephropathy, UTI and pneumocystis infections
4) Significantly Increased risk of AMR.
· What is the level of evidence provided by this article?
This is a systematic review and meta-analysis. Level of evidence is level 1.
· What are the weak and strong points of this study?
The weak points of the study are:
1) The study includes observational studies only. No RCT (randomized controlled trial) was included in the review.
2) No standard protocol was used in the different studies, hence it is difficult to compare outcomes especially regarding the effects of desensitization, immunosuppression and titre threshold.
3) Detailed datasets were not available, including patient characteristics like dialysis vintage, primary disease, cardiovascular and frailty status etc.
4) The patient cohorts were heterogeneous.
5) Various important domains, including stability of graft function, cardiovascular disease, diabetes, patient-reported outcomes could not be assessed.
The strong points of the study are:
1) The heterogeneity of the patient cohort is a strong point as the results of the meta-analysis are applicable on a large population/ geographical area.
2) Despite lack of detailed datasets, this meta-analysis gives important insights in the graft and patient survival in ABO incompatible transplants, coming to the conclusion that ABO compatible transplants have advantage over ABO incompatible transplants and hence kidney paired programs should be encouraged.
III. Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis
Summarise this article
This is a systematic review & meta-analysis of a large number of observational studies published up until Dec 31, 2017. It included a diversity of population of both adults & pediatrics.
The primary endpoints were all-cause mortality & graft survival at 1, 3, 5, & >8 years after transplantation.
ABO-i has a higher mortality at 1-, 3- & 5-year compared to ABO-c transplantation. The high mortality was related to the intense immunosuppression from desensitization treatments.
Graft survival, death-censored & death-uncensored, was lower at 3 years in ABO-i transplants.
At 5 years death-uncensored, but not death censored, graft survival was lower in ABO-i vs ABO-c transplants.
The risk of infections & surgical complications was higher in ABO-i vs ABO-c
TCMR rates was not different between both groups, however the rate o AMR was higher in ABO-i vs ABO-c transplants.
Conclusion:
Compared to ABO-c living donor, ABO-i renal transplantation is worse in all clinical outcomes.
KPD is favored in place of ABO-i transplantation.
================================================
What is the level of evidence provided by this article?
Level I
================================================
What are the week and strong points of this study?
Week points:
– Some of the consented outcomes were not addressed in the endpoints.
These included cardiovascular disease, stability of graft function, & diabetes.
– The results were not robust >5 years after transplantation.
– No randomized controlled trials.
– The effect of specific induction 8 desensitization regimen could not be
assessed.
Strong points:
– No publication bias regarding the mortality outcome.
– The meta-analysis was conclusive regarding the mortality at 1 year, 5 years
(inconclusive for mortality at >8 years).
The aim of the study;
was to investigate differences in outcome after ABOi-rTX and ABOc-rTX .
The type of the study;
This systematic review and meta-analysis .
Population;
More than 65 000 patients originating from the USA, Europe, Asia, and Australia . 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx.
Exclusion criteria;
included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-rTx.
The primary end points;
were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
The result of the study ;
Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality 3 years and 5 years following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year and 3 years only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
what is the level of evidence provided by this article ?
Level 1
What are the weak and strong points of this study ?
1-Only some items of the core outcome sets were encompassed in the primary studies and could be analyzed.
2-Other important domains, such as cardiovascular disease, stability of graft function, diabetes, or meaningful patient- reported outcomes, could not be addressed because studies included in the meta-analysis did not report them.
3-Different immunosuppressive protocols were used between studies, making it impossible to assess the effect of a specific induction and desensitisation regimen.
4- The observational periods were shorter than 5 years in most studies and therefore less data were available for the analyses of clinical outcomes after 5 years.
5-An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
6-Heterogeneity in the included study cohorts was substantial, with discordances in donor and recipient ages and immunological risk factors.
7- Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
8- Ethical considerations and administrative barriers exist and have to be taken into consideration.
Summarise this article :
1- ABOi-rTx involves a significantly higher mortality at 1,3 and 5 years post-transplantation, in comparision to ABOc-rTx. however, mortality rates and so patient survival were almost equivalent in both groups, 8 years post-transplantation.
2- ABOi-rTx involves a lower graft survival at 1,3 years post-transplantation, in comparision to ABOc-rTx. however, graft losses and so graft survival were almost equivalent in both groups, 5 years post-transplantation.
What is the level of evidence provided by this article?
What are the week and strong points of this study?
ABOi renal transplantation provides novel options for patients in need of a transplant organ with a living donor. This is a systematic review and meta-analysis of observational studies with level of evidence 1, from 40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia, published up until Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-rTx and included an ABO-compatible control group.
Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation.
Results
• Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality, 3 years, and 5 years. Following transplantation. Meta-analysis clearly shows that even with the most advanced desensitisation protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX.
• Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year.
• Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years.
• Higher rates of bleeding events are more common after ABOirTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis or highvolume plasma exchange, or both.
• The risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination with peritransplant conditioning regimens.
The observed higher early mortality after ABOi-rTx than after ABOc-rTX could be overcome by refining the initial immunosuppressive protocols and individualising the immunosuppressive therapy.
Weak points
– No randomized controlled studies identified in the search
– Cardiovascular disease, graft function stability, and diabetes were not all mentioned as outcomes in most of the studies.
– Desensitisation protocols used were not unified which makes impossible to assess their outcomes.
– The followup of most studies is for less than 5 y
– Lack of heterogenicity of studied population
– Inaccuracy of determining the accurate time of occurrence of complications
– ABOc-rTx from deceased donors was not included in the study
Strong points
– Large number of cases and studies were enrolled
– It included outcome data for graft or recipient survival available for at least 1 year or more follow-up.
– Statistical heterogenicity was detected by inspecting the forest plots and the estimates of the diversity (D²) and inconsistency (I²) statistics.
– In this study they used calculations to enable the statistical inference concerning a cumulative meta-analysis that has not yet reached the required information size to be notice.
– The funder of the study did not interfere in the study details.
– Absence of publication bias with regard to the mortality outcome
With increasing organ shortage the trend to do more ABOi- KT has emerged . The outcome of ABOi- KT and ABOc- KT needs to be assessed at early and late points. In this sytemic review the authors have investigated the difference in outcome of ABOi- KT and ABOc- KT. in this review data was analyzed from published reports.
Methodology.
This was a systemic review and meta analysis looking at outcome at>= 1 year post ABOi- KT and ABOc- KT. Data was searched on Medline Ovid , Pubmed, Central Embass Ovid. Inclusions– all studies comparing ABOi- KT and ABOc- KT
Exclusions– Case reports, Editorials, letters, meeting reports and studies where data could not be extracted .
Primary End point– Mortality at 1,3,5 and 8 years post KT
They used a fixed effect model if I2 value was 0 and both random and fixed effect model if I2
was more than 0.
Results.
About 40 studies were analyzed and it was noted that outcome was inferior in ABOi- KT as compared to ABOc- KT as regards graft survival and mortality. Graft loss were almost similar at 5 years and patient survival was similar at 8 years.
Conclusions.
In short term the outcome of ABOi- KT was poor that ABOc- KT
Level of evidence -1
Weakness of study
Short duration and non randomization
Did not include ABO compatible deceased donors.
onset of infectious and non infectious complications could not be determined
Didn’t assess the effectiveness of specific desensitization protocols
Strength of study
Meta analysis
Case reports, Editorials, letters, meeting reports and studies where data could not be extracted .
Introduction
Methodology
systematic review and meta-analysis of observational studies publish between Jan27,1998 and Set 1,2017 was looking at reported outcome data >=1 year follow up following ABOi-rTX and ABOc-rTX control group. The literature was searched by the CENTRAL, Embase Ovid, MEDLINE Ovid, and PubMed. All studies of ABOi-rTX and ABOc-rTX control group were evaluated. This study excluded ; case reports, editorials, review and letters, meeting reports, animal studies,deceased donor ABOc-rTX, non-renal solid organ and bone marrow transplant studies, and studies where data cannot be extracted. Primary outcomes were all cause mortality and graft survival at 1,3,5 and > 8 years post-transplantation. Fixed-effects model was considered when I2 = 0 and both fixed-effect and random-effects model were considered when I2>0
Results
Conclusion
Despite the advances and progress in the techniques of desensitization protocols this meta-analyses showed significant mortality and grafts loss associated with ABOi-rTX compared to ABOc-rTX at least in the short term. The outcomes appeared to be the same after 5 years.
Level of evidence = 1
Limitation of the study
1.Good points , this is systematic review and meta-analysis
2.Weak points
continue
versus the group without rituximab;
promote effective PKDE program to over come the disadvantages of ABOi -KT such as infection ,rejection and bleeding .
level of evidence 1
weakness of this study
short time duration of this study
not randomized control trial
exclude deceased ABOc -KT in the study
strength of the study
meta analysis systemic review.
proper data collection as excluded case report and others in proper data.
large number of studies comparing more than 65000 patients and 7000 whom undergo ABOi-KT were identified.
no publication bias was detected.
summary
ABO incompatibility is increasing used to overcome organ shortage.
this systemic review investigate difference in out come after ABOi-rTX and ABOc-rTX.
Data were extracted from published reports.
primary endpoint were all cause mortality and graft survival at 1.3.5 and 8 years after transplantation
comparing ABOi-rTX and ABOc-rTX the result is higher mortality 1.3.5years following transplant
mortality attributed mainly to intensify immunosupressin therapy which result in infection such as viral (CMV) and bacterial ,in addition to bleeding mainly realted to use of anti coagulation during plasmapharesis
also death-censored graft survival has lower with ABOi-rTX with ABOc-rTX at 1 year and 3 year . only graft loss were equivalent to that of ABOc-rTX after 5 years and patient survival after 8 year.
incidence of AMR is higher in patient with ABOi- than ABOc years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group versus the group without th
.
1- Summary
Smaller studies adressing patient and graft outcome after ABOi-rTx did not show any differences compared with living donor ABO-compatible renal transplantation (ABOc-rTx), larger registry data results were equivocal.
This study is a systematic review and meta-analysis of the published data to evaluate if the effects of ABOi-rTx in terms of graft survival, patient survival, and infectious and non-infectious complications are comparable to that of ABOc-rTx, taking into consideration the different desensitisation strategies .
Results
It showed that ABOi-rTx was associated with a higher risk of 1-year , 3-year and 5-year mortality , but not of 8-years or more mortality when compared with ABOc-rTx .
Sepsis was higher after ABOi-rTx than after ABOc-rTx but there was no statistically significant difference in the risk of urinary tract infections , cytomegalovirus infection , BK polyomavirus infection , and P jirovecii pneumonia.
No significant difference in the number of ABOi-rTx patients with surgically treated lymphocoeles or ureteral complications and those with ABOc-rTx meanwhile surgical revisions for hematoma ,lymphocele and surgical complications were more in ABOi-rTx group.
No significant difference between both groups regarding overall , borderline , or T-cell mediated rejections but ABMR rate was higher after ABOi -rTx than after ABOc-rTx
Rituximab-based versus non rituximab-based desensitation protocols revealed higher 1-year and 3-year mortality after ABOi-rTx than after ABOc-rTx apart from the initial desensitisation protocol
5 years after transplantation, ABOi-rTx was not associated with significantly higher mortality than was ABOc-rTx in the rituximab group versus the group without the rituximab.
In groups with rituximab usage in desensitisation, death-censored graft survival at 1 year and 3 year was equal between ABOi-rTx and ABOc-rTx groups while in cases of densenstisation without rituximab usage death-censored graft survival at 1 year and 3 year was worse in the ABOi-rTx than ABOc-rTx groups.
Rituximab usage in desensitisation protocols or not didnot reveal significant difference regarding graft survival data after 5 years between the 2 groups.
In non-rituximab-based desensitisation protocols ,sepsis and cytomegalovirus infections risk after ABOi-rTx was significantly higher than after ABOc-rTx, but no difference was seen between the 2 groups in those who received rituximab-based desensitisation protocols
A trend for higher risk for polyoma nephropathy was noticed after ABOi-rTx than after ABOc-rTx in patients who received rituximab-based desensitisation protocols.
Concerning P jirovecii pneumonia and urinary tract infections, no significant differences were detected between ABOi-rTx and ABOc-rTx with either of the desensitisation protocols.
A higher risk of ABMR after AB0i-rTx than after AB0c-rTx with both desensitisation protocols was noticed but it was significantly lowered if rituximab based protocol was applied.
Discussion
The study demonstrated that ABOc-rTx has better outcome than ABOi-rTx in the first 5 years after transplantation but after 8 years equal otcomes was noticed for survivors of the 2 groups.
In rituximab based protocols mortality with ABOi-rTx was only seen within the first 3 years, and death-censored graft survival became similar to that of ABOc-rTx within the first year.
The study showed that with the introduction of different advanced desensitisation protocols, mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX due to overimmunosuppression , life threatening infection and higher risk of bleeding and surgical complications ,this can be solved by individualising immunsuppresion protocol , as in some studies concluding that using lower doses of immunosuppression can decrease infection risk and won’t increase the rejection risk ,leading to favourable overall outcome.
Paired kidney exchange program is the other choice for cases fit for ABOi rTx
2- level of evidence is I
3-Strong points are
-that the systematic review and the meta-analysis were done according to the most accepted practices regarding assessment of study quality and risk of bias.
-Large number of cases and studies were enrolled
-It included outcome data for graft or recipient survival available for at least 1 year or more followup .
-Statistical heterogenicity was detected by inspecting the forest plots and the estimates of the diversity (D²) and inconsistency (I²) statistics.
-In this study they used calculations to enable the statistical inference concerning a cumulative meta-analysis that has not yet reached the required information size to be noticed
-The funder of the study did not interfere in the study details.
-Absence of publication bias with regard to the mortality outcome
Weak points are
-the evidence given has the inherent drawbacks of observational studies and there was no randomised controlled studies identified in the search
-Not mentioning all consented fundamental outcome items for studies of kidney transplantation as cardiovascular disease, graft function stabiliy, and diabetes.
-Ununified desensitisation protocol used rendered it impossible to assess their outcomes.
-Most studies followed the cases for less than 5 y and small centre studies were not excluded
-Lack of heterogenicity of studied population
-Inaccuracy of determining the accurate time of occurrence of complications
-ABOc-rTx from deceased donors was not included in the study
Summary
ABO incompatible (ABO-i) kidney transplant is increasing to overcome the shortage of organs from deceased donors, this was enabled by desensitization strategies.
Results of studies comparing the outcome of ABO compatible (ABO-c) and ABO-i kidney transplants are controversial.
The safety and outcome of ABO-i kidney transplants are not well determined.
A meta-analysis and systemic review of observational studies reporting the outcome of ABO-i kidney transplant after one year or more of follow up and included ABO-c transplants as control group.
Predefined primary outcomes were graft survival and all-cause mortality at 1,3,5 and 8 years post transplant.
secondary outcomes were infectious and non infectious complications and graft rejections.
It showed that
ABO-i renal transplant is associated with poorer graft survival and higher immunological risk.
ABO-c transplants are more beneficial than ABO-i transplant in the first 5 years with similar long-term outcome.
Patient mortality was higher in first 5 years with ABO-i renal transplant than with ABO-c transplants.
ABO-i transplants are associated with higher risk of AMR.
ABO-i transplants had higher rates of bleeding events, wound infection, hematomas and surgical revisions.
Decrease of initial immunosuppression may decrease early mortality rates in selected patients
ABO-i transplants are associated with significant higher risk of polyoma nephropathy than in HLA incompatible transplants.
ABO-i transplants with rituximab based desensitization protocols have the same risk of AMR as in ABO-c transplants 5 years post transplant.
Type of study meta-analysis systemic review
level of evidence 1
Strength
Meta-analysis systemic review
Excluded case reports, editorial reviews and studies with unextractable data
Limitations
Couldn’t analyze all outcome data in studies of kidney transplantation.
Couldn’t assess the effectiveness of specific desensitization regimens.
Most studies have short observation period less than 5 years so failed to analyze the outcome after 5 years.
Possibility of duplication due to inclusion of patient cohorts in national registry analysis and smaller single-centre studies.
Didn’t state the time of complication post transplant.
Patients characteristics were not reported in most studies and they may affect transplant outcome.
Didn’t include ABO-c transplants from deceased donors.
Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis.
This systematic review and meta-analysis for 40 eligible studies for assessing clinical outcomes of ABOi-rTx in comparison with ABOc-rTx which comprising more than 65000 patients, 7000 of whom had undergone ABOi-rTx.
All studies were published between Jan 27, 1998, and Sept 1, 2017 were included considered to be drawbacks of observational studies and references identified by database searches.
Introduction:
ABO-incompatible renal transplantation is considered one option which contributes to shorten the time of potential kidney recipients on waiting list specially with promising graft and patients survival with the new strategy of desensitization specially for patients with end-stage renal disease presenting with a living donor with an unsuitable blood group.
Data analysis:
Predefined primary outcomes were graft survival and all-cause mortality at 1, 3, 5, and more than 8 years after transplantation.
Secondary outcomes were infectious and non-infectious complications, and graft rejections.
Results:
=37 (65 063 participants) for 1 year.
=27 (44 213 participants) for 3 years.
=15 (56 640 participants) for 5 years.
=Three studies (11 039 participants) for more than 8 years were included in the analysis of mortality after transplantation.
* ABOi-rTx was associated with a higher risk of 1-year mortality , 3-year mortality , 5-year mortality, but not of 8-years or more mortality.
* At 1 year, death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx , as was death-uncensored graft survival.
* At 3 years, death-censored and death-uncensored graft survival was lower after ABOi-rTx than after ABOc-rTx.
* Death-uncensored but not death-censored graft survival was lower after ABOi-rTx than after ABOc-rTx.
* The proportion of patients with sepsis was higher after ABOi-rTx than after ABOc-rTx.
* A greater proportion of patients who had ABOi-rTx had surgical revision than those who had ABOc-rTX, bleeding or hematomas , and lymphoceles.
* No significant difference between treatment groups was observed in overall , borderline , or T-cell mediated rejections
* By contrast, the proportion of patients with ABMR was higher after ABOirTx than after ABOc-rTx.
* Higher 1-year and 3-year mortality after ABOi-rTx than after ABOc-rTx regardless of the initial desensitization protocols (with or without Rituximab).
* There was a trend for a higher risk of ABMR after AB0i-rTx than after AB0c-rTx with both desensitization protocols.
Discussion:
Systemic review and meta-analysis of 40 studies including more than 65000 patients which generally shown The clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation.
Only long-term data after 8 years indicate equal performance of the procedures for survivors.
Statistical analysis shows that even with the most advanced desensitization protocols, patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX so PKD should be considered as a great option before shifting to ABOi TX or be complementary together.
Higher rates of surgical complications specially bleeding events are reported after ABOirTx than after PEX or immunoadsorption.
Higher early mortality after ABOi-rTx than after ABOc-rTX could be overcome by refining the initial immunosuppressive protocols and some studies with lowering IS has the better outcome with less infectious complications and without increased incidence of acute rejection.
The risk of ABMR with rituximab-based desensitization protocols was clearly reduced (in comparison with splenectomy) and the risk of ABMR in the ABOi-rTX group was similar to that in the ABOc-rTX group 5 years after transplantation if rituximab was initially used.
Similar results were obtained in immunologically high-risk recipients of ABOc-rTx given rituximab within the course of induction therapy.
The alternate option to ABOi-rTx would be paired kidney exchange, or even more complex scenarios have been successfully managed, such as three-way and multiple-way kidney exchanges. Our results should encourage clinicians, health-care providers, and health policy makers to facilitate and expand the network of kidney exchange programs.
a systematic review and meta-analysis
Level of evidence I.
Limitations or weakness:
– Cardiovascular disease, stability of graft function, diabetes, or meaningful patient reported outcomes, could not addressed.
– The observational periods were shorter than 5 years and so less data were available for the analyses of clinical outcomes after 5 years.
Strength points:
– meta-analysis level evidence .
-Large number of studies and large number of patients.
-multiple centers international experience.
Systemic review & meta-analysis, level 1
Due to shortage of both deceased & live donor pools, the ABOi transplantation became an accepted option to overcome this shortage.
Aims of the study:
Method:
It is a systemic review & meta-analysis ( PROSPERO protocol. Include 40 studies (65000 patients) of pediatric & adult ABOi transplantation with AbOc patients as control group from USA, Europe, Asia & Australia, with follow-up for >1 year.
Exclusion include case report, editorial, review & letters, animal studies, meeting paper, non renal solid organ transplant & bone marrow transplant & non English studies.
Primary outcome: graft survival & all cause mortality at 1,3,5 & > 8years.
Secondary outcome: infectious( sepsis, UTI, CMV, BK virus, P. jirovecii ) & non infectious ( surgical revision, hematoma, lymphocyte, ureteral) complication & graft rejection.
Results & discussion:
Limitations of the study:
This is a systematic review and meta-analysis of observational studies including 65 063 patients
Addressing graft and patient survival 1, 3, 5, and more than 8 years after transplantation In ABO-incompatible transplantation
Results and conclusion
ABOi when compared to ABO-compatible transplantation is associated with the following :
What is the level of evidence provided by this article?
What are the week and strong points of this study?
CLINICAL OUTCOMES AFTER RENAL TRANSPLANTATION INVOLVING ABOI
Mortality in the patients transplanted from ABO incompatible donor is higher at 1, 3 and 5 years post-transplant than the patients transplanted from ABO compatible donor, and become the same at 8 years post transplant, this mostly related to side effects of heavy immunosuppression given to these patients like infections either bacterial and viral like BK virus, CMV, coagulation disorders.
the incidence of AMR is higher in the patient with ABO incompatible donor than those with ABO compatible donor in spite of heavy immunosuppression and giving rituximab.
level of evidence 1
strong points it is large number of studies from different areas allow diversity of the patients and results.
weak points lack of randomized clinical trials, there are some endpoints not mentioned or addressed by the studies like cardiovascular risk, DM, graft function stability, also different protocols of immunosuppression allow impossible comparison to get right assessment based on specific immunosuppressive protocol, also years of follow up was 5 years only, not extended to be longer than that
Thank you Riham
That is how to summarise an article, basically, we need to know your understanding. I will wait for others to reply.
Parameters compared between ABOi and ABOc transplant –
graft survival
patient survival
infectious complications
non-infectious complications
systematic review and meta-analysis was done according to the PROSPERO protocol.
Inclusion criteria –
studies of paediatric or adult recipients of ABOi-rTx
if an ABO-compatible control group was included
if outcome data for at least graft or recipient survival with 1 year or more of follow-up were available.
Exclusion criteria –
case reports
editorials
reviews and letters
animal studies
meeting papers
studies with unextractable data
non-renal solid organ transplant studies
bone-marrow transplant studies.
Non English articles
40 studies involving more than 65000 patients originating from the USA, Europe, Asia, and Australia were included.
The statistical analyses reveal a clear benefit of ABOc-rTx over ABOi-rTx in the first 5 years following organ implantation.
Only long-term data after 8 years indicate equal performance of the procedures for survivors.
With use of rituximab instead of splenectomy excess mortality with ABOi-rTx was only seen within the first 3 years, and death-censored graft survival became similar to that of ABOc-rTx within the first year.
patient mortality is higher in the first 5 years after ABOi-rTx than after ABOc-rTX due to emergence of life threatening infections due tp over suppressed immune system.
Higher rates of bleeding events are reported after ABOirTx than after ABOc-rTX, probably due to changes of the coagulation system following plasmapheresis.
Surgical revisions, with more postoperative wound infections, haematomas, and lymphocoeles are more common after ABOi-rTx.
The risk of postoperative bleeding appears to be especially high if immunoadsorption is used.
risk of serious infections and infection related mortality increases considerably if rituximab is used at higher doses or in combination.
Stately to decrease infection risk and mortality include-
reduced dose of rituximab
no rituximab
no plasmapheresis during the induction phase
lower doses of mycophenolate mofetil during the
maintenance phase.
The lower (death-censored) graft survival with ABOi-rTx
was in line with a high risk of ABMR.
Polyoma nephropathy was more common after ABOi-rTx
than after ABOc-rTX in patients who received rituximabbased desensitisation protocols.
The risk of developing polyoma virus-associated nephropathy in patients who have undergone ABOi-rTx is even significantly higher than in recipients of HLA-incompatible kidney transplants.
The improvement in graft survival at 3 years in the
ABOi-rTx group that received rituximab mainly reflects
evolution in the preconditioning procedure.
Patients undergoing ABOi-rTx are at higher immunological risk because of –
re-transplant condition
older age
unrelated donors
more HLA mismatches
higher panel reactive and donorspecific antibody amounts.
risk of ABMR in the ABOi-rTX group was similar to that in the ABOc-rTX group 5 years after transplantation if rituximab was initially used.
Limitations-
endpoints did not address all consented core outcome
domains for studies of kidney transplantation.
Different immunosuppressive protocols were used
between studies, making it impossible to assess the effect
of a specific induction and desensitisation regimen.
The observational periods were shorter than 5 years in most studies.
Duplication of patient data is a possibility.
An accurate report of the time after transplantation at which infectious, non-infectious, and immunological complications occurred was not stated.
Differences in patients’ characteristics that might have an effect on transplantation outcomes, such as frailty status, duration of dialysis before transplantation, cardiovascular disease burden, and primary diseases, were not reported in most of the studies.
The alternate option to circumvent ABOi-rTx would be
paired kidney exchange, which has been established in
numerous centres.
level 1 evidence