II. Clinical Relevance of Pretransplant Testing for Anti-Human Leukocyte Antigen Antibodies in Iraqi Renal Transplant Patients
This study showed that the information obtained through pretransplant antibody testing is essential for making transplant decisions and for facilitating transplant in sensitized patients through proper selection and well-designed immunosuppression protocols.
- How did the authors make this conclusion?
- Critically appraise this article.
- What is the level of evidence provided by this study?
The study was done in IRaQ and they concluded that : pretransplant testing for anti-HLA antibodies is undoubtedly useful for the assessment of patient risk, to facilitate decisions regarding patient and donor selection, and to plan treatment strategies. The 1-year survival rate for sensitized patient was lower than for nonsensitized patients. More knowledge, experience, technologic advance- ments, and support are needed to improve the Iraqi practice of transplanting sensitized patients.
Study was conducted on 336 patients who were living donor ,blood group compatible ,tested by complement dependent cytotoxicity and by the Luminex for anti-HLA antibodies .
donors are living-donor, blood group-compatible donor .
They divided the patients into 2 groups :sensitized and non sensitized
desensitization was done with plasmapheresis, IVIG and rituximab with rATG for induction while basiliximab was used for induction in non sensitized recipients.
sensitization mostly due to blood transfusion .
it is level 2 of evidence ,limitations include:Follow up was only within 1 year ,small sample size
This study is a cross-sectional study, with level 3 to 4 of evidence. I think with this study we cannot draw this conclusion, and we need studies with more robust and precise design and higher levels of evidence such as clinical randomized trials for drawing such a conclusion. This study is only a report of kidney transplantation in one center and evaluated the effect of using Luminex assay for immunological assessment on transplantation outcomes without any control group for comparison or even true randomization.
The study was conducted in medical city,Baghdad, Iraq to study the effect of sensitization befor Tx on long term graft survival.
They included 336 patients who were tested by complement dependent cytotoxicity and by the Luminex for anti-HLA antibodies .
donors are living-donor, blood group-compatible donor .
All transplant patients (sensitized or not) were followed for 1 year( short period).
The patients are divided into 2 groups sensitized and non sensitized patients positive CDC are excluded from this study while positive luminex and DSA patients are considered sensitized group they were 63 patients. desensitization was done with plasmapheresis, IVIG and rituximab with rATG for induction while basiliximab was used for induction in non sensitized recipients.
sensitization mostly due to blood transfusion .
no hyperacute rejections in all patients
graft survival is better in non sensitized patients for one year post transplant which is short period.
No follow up of post transplant DSA
Therefore study of pre-transplant anti-HLA antibodies helped in determining immunosuppression protocol and desensitization improved graft survival over the 1 year period of the study .
prospective cross sectional study level of evidence 2.
Small sample size.
Short follow up period.
Clear method and conclusion
The study include 63 sensitized potential renal transplantation recipients, only 13 patients received renal transplantation after desensitization. 2 of these sensitized patients are died while waiting for more compatible donor. The study show that transplantation of sensitized patients was associated with better graft & patients survival when compared to patients who were waiting for more suitable donor.
Cross sectional study, level 2.
Aim of the study: Impact of pre-transplantation assessment of sensitization on patients & graft outcome.
The study included 336 potential renal transplantation recipients, only 63 of them are sensitized. Most of sensitized patients were below age 40 (74.3%), mostly female (60%). Desensitization by PP, IVIG & rituximab. High risk recipients induction with ATG with maintenance therapy based on CNI, MMF & steroids. Acute rejection diagnosed by histopathological finding on graft biopsy ( Banff 97).
The sample size was small & follow-up period limited to 1 year
It’s a prospective cross sectional study with level of evidence 2 , the study explained the effect of sensitisation on graft function and survival.
The study has been done in medical city,Baghdad, Iraq by following 336 patients who are candidates for kidney transplant most of them are below the age of 40 years old .
The patients are divided into 2 groups sensitized and non sensitized patients by doing CDC and luminex test patients with positive CDC are excluded from this study while positive luminex and DSA patients are considered sensitized group treated by desensitization protocol with plasmapheresis, IVIG and rituximab with rATG for induction while basiliximab has been used as induction therapy for non sensitized patients,without mentioning the donor characteristics like whether relative or no and the donor age .
Most sensitized patients are due to blood transfusion .
There is no hyperacute rejection in all patients but graft survival is more better with 90% in non sensitized patients and 61.1% in sensitized patients but this follow up is just for one year post transplant which is short period.
How did the authors make this conclusion?
The study was performed among 336 transplant recipients with or without history of sensitization. Sensitized patients were transplanted after desensitization{ intravenous immunoglobulins, plasmapheresis, and Rituximab} . positive CDC were excluded from transplant The study showed that the sensitized patients had poorer graft survival than the non-sensitized patients. Protocol biopsies were not done and there is no mention of post-transplant DSA in the study.
Critically appraise this article.
This study show that pre-transplant anti-HLA antibody evaluation has a role in management of sensitized patients. The study was relevant with respect to the cohort of patients in the country of study. The study included 336 patients but only 172 complete the study this reflect on the power of this study . the follow-up term is just one year, lengthier follow-up periods are required. The study answered the questions and made aconclusion , pretransplant testing for anti-HLA antibodies is undoubtedly useful for assessment of patient risk, to facilitate decisions regarding patient and donor selection, and to plan treatment strategies .
What is the level of evidence provided by this study?
The level of evidence provided by this study is level 2: Prospective cohort study.
How did the authors make this conclusion?
Pretransplant testing for anti HLA antibodies is useful for assessment of patient’s risk, the need for desensitization, and follow up after desensitization. in addition to follow up post transplantation.
Critically appraise this article.
Abstract, title and references:
the aim of the study is clear( to understand how much the testing for pretransplant anti-HLA antibody could affect the decision of transplantation and 1 year survival.
The findings of the study are clear and the authors made it clear how they did them.
The references are relevant, recent and referenced correctly.
Introduction:
The authors made it clear( what is already known about anti HLA antibody testing, HLA typing, and cross matching testing).
The research question( is testing for anti HLA antibodies important for transplantation outcome) is clearly outlined and justified.
Methods:
patient selection is clear.
All the variables are well defined and measured.
The study methods are valid and reliable.
There is enough information to repeat the study in future.
Results:
Tables and figures are relevant and clearly presented.
Titles are labeled correctly and clearly.
Categories are grouped appropriately.
The findings are clear ( 1 year survival rate of sensitized and non sensitized patients).
Discussion and conclusion:
The results are discussed appropriately without being over interpreted.
The conclusions answer the aim of the study and are supported by references.
No fatal limitations to this study.
Overall:
the study design was appropriate to answer the aim of this study and the article is consistent with itself.
What is the level of evidence provided by this study?
This is e retrospective cohort study, level of evidence II.
The introduction of the paper is informative. The study itself evaluated according to the time it was performed is good and not underpowered in terms of number. The handicap was the refusal of protocol biopsies which underpowered the value of the study in relation to giving real information about the probable clinically non-obvious rejections (subclinical rejections). as far as we know the eGFR will be affected later.
one limitation is that the exact question is not clear. the aim was to evaluate the effect of pretransplant testing by LUMINEX but the evaluation may have missed non-biopsied cases.
*** The authors did not mention limitations of the study
This is very short Mahmud
I will extend that inshaallah
The authors studied 336 transplant recipients in Iraq From January 2014 to June 2017. All of them performed CDC and Luminex and all of them received kidneys from living blood compatible donors. They were followed for 1 year. Sensitized patients were 63(18.75%) and DSA were present in 52.3% .The decision to use which drug for induction whether antithymocyte globulin or basiliximab was dependent on the result of antibody testing. 15.3% (13 patients )of the sensitized patients underwent transplant .Non sensitized patients received basiliximab then calcineurin inhibitors, myco phenolate mofetil, and steroids. Sensitized patients with positive CDC were excluded from transplant while sensitized with positive Luminex and DSA underwent desensitization by intravenous immunoglobulins, plasmapheresis, and rituximab .There was no case of hyper acute rejection. The 1 year survival of sensitized patient was 61.5% compared with 90% for non sensitized.
Critically appraise this article.
The study started with 336 patients and only 172 completed the study (159 of 273 non sensitized and 13 out of 63% sensitized) . This will affect the power of the study. Those who were not transplanted need to be evaluated. So the study design in the start was a retrospective cohort but the authors focused only on those who underwent transplantation. He stated it is cross sectional but it looks like an observational comparative more than a cross sectional.The research question included two aspects one was the survival after one year which was precisely answered by the end of the study . The other domain was to understand how much the testing for pretransplant anti-HLA antibodies affects the decision for transplant. This objective was phrased in a non measurable terminology. It needed more specifications. Actually they measured the decision of induction type of medication. In the study the auhors said that those tested negative received induction with basiliximab and maintenance with triple therapy. While they did not specify in clear terminology what induction the sensitized patients received. They have mentioned at one point that the decision to choose between ATG and basiliximab was based on antibody testing. Secondary outcomes , DGF, ACR and AMR were more in the sensitized group but the authors did not mention the statistical significance of these differences.
What is the level of evidence provided by this study?
VI (Evidence from a single descriptive or qualitative study.)
THANK YOU All FOR YOUR CONTRIBUTIONS
Through implementation of CDC and Luminex technique ,one 1 year follow up of Tx of sensitized patients with desensitization(negative CDC and positive SAB Luminex to detect DSA), authors had their conclusion. Pre transplantation risk stratification influences Tx decision and post Tx care plan.
Critical appraisal
-Small desensitized group(13/63)
-Age as patients less than 40 years represent 60% affecting risk of ABMR
-Short duration of follow up ;1 year
-Unavailability of FCXM
Level of evidence 2 as it is prospective cohort
This is very short Ahmed
The study involved 336 patients with and without history of sensitization(blood T r and multiparity).Those with positive CDC were excluded; and for who were sensitized, desensitization done by IV Ig, plasmapheresis and rituximab.IS in non sensitized patients included basiliximab, then CNI ,MMF and steroids. Sensitized patients had increased incidence of ABMR (6 PATIENTS OF 13).
It was found that 1 year survival of sensitized patients was lower (61.5%) in comparison to that of non sensitized patients(90%).In sensitized patients, careful decision for transplantation should include thorough patient evaluation including DSA assay, desensitization ,induction therapy and proper maintenance IS with DSA monitoring with IS modulation according to graft biopsy if needed.
The study is prospective cohort exploring Tx outcome considering condition of sensitization .Level of evidence 2.
How the authors make this conclusion?
To minimize hyperacute antibody-mediated rejection, very sensitive Luminex technology was used to detect immunologic risk in kidney transplant candidates. Our goal was to learn how pretransplant anti-HLA antibody testing influences transplant decisions and 1-year survival.
Methods: From January 2014 to June 2017, our nephrology and renal transplant clinic evaluated 336 transplant candidates for HLA antibodies using the Luminex technology (The Medical City, Baghdad, Iraq). Clinical and laboratory data were recorded. Our program accepts live, blood group-compatible donors.
The Kaplan-Meier approach was used to calculate the survival rate of all transplant patients, sensitive or not.
The research group’s mean age was 34.07 12.4. There were 63 sensitized individuals (18.75%) and 159 nonsensitized patients (47.35%) out of 336 tested. Sensitization was caused by a blood transfusion. Anti-HLA antibodies were found in 54 of 63 sensitized individuals (85.7%) and 39 of 63 sensitized patients (39.3%). (61.9 per cent). 33/63 had donor-specific antibodies (52.3 per cent). 13 hypersensitive individuals (15.3%) had transplants. No hyperacute rejections were noted. The nonsensitized patient group had 90% 1-year survival, whereas the sensitized patient group had 61.5 per cent.
Pretransplant anti-HLA antibody testing is clearly valuable for assessing patient risk, deciding on patient and donor selection, and planning treatment methods.
Sensitized patients had shorter 1-year survival than nonsensitized patients. Transplanting sensitive patients in Iraq requires more knowledge, expertise, technology, and assistance.
critical appraisal:
-Only 13 instances were desensitized out of a total of 63 sensitized cases, hence the desensitized group is too small to draw any conclusions.
-It was not possible to use flow cytometry or complement-fixing anti-HLA DSAs or non-HLA antibodies since they were not accessible.
-the follow-up term is just one year, lengthier follow-up periods are required.
level of evidence:
– it is prospective cross-sectional research, the level of evidence is 2.
This study showed that the information obtained through pretransplant antibody testing is essential for making transplant decisions and for facilitating transplant in sensitized patients through proper selection and well-designed immunosuppression protocols.
1. How did the authors make this conclusion?
The study was performed among a cohort of transplant recipients with or without history of sensitization. Sensitized patients were transplanted after desensitization. The study showed that the sensitized patients had poorer graft survival than the non-sensitized patients. The sensitized group had wide MFI range of class I and II antibodies and had increased incidence of AMR (6 out of 13). Patients who were CDC positive were not transplanted, sensitized patients were transplanted after desensitization. Protocol biopsies were not done and there is no mention of post-transplant DSA in the study.
In light of these findings it is appropriate to select transplant candidate among sensitized patients carefully after proper counselling of the patient as well as detailed evaluation, including single antigen bead assay for measuring the level of DSA. The protocol for managing sensitized patients should be defined and involve desensitization, induction and maintenance immunosuppression. But, equally important is the post-operative follow-up, especially DSA monitoring and protocol biopsy, if required.
2. Critically appraise this article.
Looking at the various parameters:
The question here is whether pre-transplant anti-HLA antibody testing is relevant in kidney transplantation. This is a relevant question as it has a bearing on the transplant outcomes.
This study would add to the data available which shows that pre-transplant anti-HLA antibody evaluation has a role in management of sensitized patients. The study was relevant with respect to the cohort of patients in the country of study.
The research question identifies the target population (Sensitized patients), Studied parameter (presence of anti-HLA antibodies and transplantation after desensitization) and the outcome of interest (graft survival)
This study was a prospective cohort study, comparing results of transplantation in kidney transplant recipients with respect to their sensitization status. This study design was appropriate. It could have been better with adding FCXM in pre-transplant workup, but the technology was not available in the country of study.
The methodology was simple with clinical and laboratory parameter follow-up of the patients. There is no scope of bias in the methodology as the test methods were defined and the data was taken from electronic database.
Yes.
Yes. The investigators were trying to find out the relevance of pre-transplant antibody testing with respect to transplant outcomes.
Yes
Yes. But there are mistakes in the data presented in the paper (Table 4).
Yes.
No.
3. What is the level of evidence provided by this study?
The level of evidence provided by this study is level 2: Prospective cohort study.
Level of evidence is 2
This study showed that the information obtained through pre-transplant antibody testing is essential for making transplant decisions and for facilitating transplant in sensitized patients through proper selection and well-designed immunosuppression protocols.
This study illustrated the results of Luminex testing of 336 patients for nearly 3 years , following them for 1 year and showed that testing of anti-HLA antibody affects the decision of transplant and the 1-year survival graft survival by performing CDC and Luminex to 20 donors.
Non-sensitized patients received induction therapy of simulect and triple maintenance therapy Tac , MMF , steroids .Sensitized patients are at higher risk of hyper acute rejection .
Sensitized patients were desensitized by intravenous immunoglobulins, plasmapheresis, and rituximab .
The results revealed that better 1-year graft survival rate of nonsensitized patients .
Critically appraise this article.
It was a cross-sectional study
The study targeted to identify the importance and impact of testing for pre-transplant anti-HLA antibodies on the transplant decision and one year survival .The study included 336 patients
Total number of patients was
important potential confounders is Absence of flow cytometry cross match
How did the authors make this conclusion?
In this prospective study, the authors evaluated the outcomes at one year of sensitized patients, based on the results of CDC and SAB luminex technique. Most sensitized patients were young, female 60%.
Sensitization is linked to multiparity and/or blood transfusion. Patients with positive CDC crossmatch were not transplanted. Patients who were defined as sensitized based on Luminex were desensitized and received CNI based maintenance therapy.
Results: Detection of DSAs in recipients using solid phase assays- Luminex with negative pretransplant CDC a increases the risk of acute antibody mediated rejection. That’s why pretransplantation stratification of patient based on the presence and strength of DSA affect the decision of transplantation.
Critically appraise this article
• Aim was evaluate renal outcomes at one year in sensitized patients using Luminex technoque
• It is a prospective cross-sectional study.
• Mean age of studied population was 30years.
• Most patients were female 60%.
• Sensitization was attributed mostly to blood transfusion of multiparity.
• No flow cytometry typing or cross match was performed.
• Desensitization of sensitized recipients was performed using intravenous immunoglobulins, plasmapheresis, and rituximab
• The authors used Kaplan-Meier Graft Survival Analyses at 12 Months in sensitized recipients.
What is the level of evidence provided by this study?
Level of evidence 2
How did the authors make this conclusion?
Fifty patients of the 63 sensitized patients were below the age of 40 years and the characteristics of the immune system in younger patients may represent another challenge in tailoring immune suppression and in planning immune monitoring .
On the other hand1.2% of patients over a 5-year transplant period were older than 60 years and the risk of antibody-mediated rejection in older patients with moderate sensitization is less compared with patients below 40years.
Also there were 38 female patients (60.3%) in the sensitized group of patient ,this can be explained by multiparity and probably by the common practice of blood transfusion with delivery.
Only 13 of 63 sensitized patients underwent renal transplant with desensitization . Two patients died waiting for transplant. This may indicate improvement in dialysis services but can also unfortunately indicate the difficulty in mitigating immune barriers in renal transplant in limited resource situations.
Critically appraise this article.
The aim of the study ;
was to understand how much the testing for pretransplant anti-HLA antibodies affects the decision for transplant and survival at 1 year posttransplant.
Study area; (The Medical City, Baghdad, Iraq).
Study design ; It’s a cross-sectional study
Population ;
Total number of patient is 336
Mean age of the study group was 34.07 ± 12.4 years
Outcome factors are AR avoided in those who are sensitized, measure by biopsy.
important potential confounders is Absence of FCXM, one year time CAI can not
be assessed.
statistical method ;
used in the study, Kaplan-Meier Graft Survival Analyses at 12 Months in Sensitized and
Conclusions:
Pre transplant testing for anti-HLA antibodies is undoubtedly useful for assessment of patient risk, to facilitate decisions regarding patient and donor selection, and to plan treatment strategies. The 1-year survival for sensitized patient was lower than for no sensitized patients.
What is the level of evidence provided by this study?
Level of evidence is 2 as it is a prospective cross- sectional study
Your reply is more consiced. Well done
thanks professor
1. How did the authors make this conclusion?
The 1-year graft survival rate of nonsensitized patients was 90%, whereas the rate of
sensitized patients was 61.1%.
affects the decision for transplant and survival at 1 year post transplant.
Outcome factors are AR avoided in those who are sensitized, measure by biopsy.
be assessed.
Kaplan-Meier Graft Survival Analyses at 12 Months in Sensitized and
Conclusions:
Pretransplant testing for anti-HLA antibodies is undoubtedly useful for assessment of
patient risk, to facilitate decisions regarding patient and donor selection, and to plan
treatment strategies. The 1-year survival for sensitized patient was lower than for no
sensitized patients.
Level of evidence 2 .
HLA typing and test for the presence of DSA is crucial step in pre transplant evaluation and selection of donor and recipient.
In addition, graft survival at 1 year is lower in sensitized patient than non-sensitized patients.
Sensitization is due to multiple transplant, multiple pregnancies, blood transfusion should be managed when cross match becomes positive to guard against hyperacute rejection which leads to immediate graft loss.
level 3 evidence
-HLA antibodies detection correlate with long-term graft failure with the risk of developing chronic antibody-mediated rejection, transplant glomerulopathy, and chronic allograft dysfunction.
Sensitised patients are at high risk of hyperacute rejection so they wait for longer periods to find a crossmatched donor.
This study demonstrated the results of Luminex testing of 336 candidates with living donor for nearly 3 years , following them for 1 year and showed that testing of anti-HLA antibody affects the decision of transplant and the 1-year survival
By performing CDC and Luminex tests to 20 donors including most HLA antigens.
Flowcytometry and complement-fixing anti-HLA DSAs and non-HLA antibodies detection are not available in Iraq.
Nonsensitized patients received induction therapy of basiliximab as induction therapy and maintainence therapy calcineurin inhibitors, mycophenolate mofetil, and steroids.
Sensitized patients were desensitizated by intravenous immunoglobulins, plasmapheresis, and rituximab .
The results revealed that 1-year graft survival rate of nonsensitized patients was higher than sensitized patients
Desensitizing highly sensitised patients provided survival benefit for them , compared with waiting for a compatible organ.
The presence of DSAs-solid phase antibodies with negative pretransplant CDC and flow cytometric crossmatches increases the risk of acute antibodymediated rejection .
This is how the authors concluded this conclusion
– 60 % of the patients age was less than 40 years and the risk of antibody-mediated rejection in older patients with moderate sensitization is less compared with patients below 40 years making the studied group less representative
Only desensitising 13 cases of 63 sensitised cases ,so the desensitised group is small in number to be conclusive .
Flowcytometry and complement-fixing anti-HLA DSAs and non-HLA antibodies was not available
The follow up period is 1 year so longer follow up periods are needed.
-Level of evidence is 2 as it is a prospective crossectional study