Introduction:
– Our bodies become sensitized in 3 main ways, pregnancy, blood transfusion, and previous transplantation. ABO-incompatible transplant in sensitized recipient is associated with increased risk for ABMR and inferior graft outcomes.
– ABOi transplant is one of the strategies done to overcome the donor pool shortage. It could by done after the development of advanced techniques regarding the detection of preformed antibodies, decreasing their levels, and subsequent management preventing their new formation.
-In this study, 66 kidney recipients were evaluated for HLA sensitization before receiving ABOi graft. HLA sensitization was tested by CDC-XM, FC-XM, single antigen bead using Luminex and finally, lysate-based solid phase crossmatch. Anti ABO abs were detected by gel cards (neutral gel cards for ABO IgM and AHG for IgM).
– Then they were prospectively included, they were divided according to their risk as group A with MFI <1000 and high-risk group with MFI > 1000. The induction regimens were basiliximab or ATG for sensitized patients. All were maintained on triple immunosuppression including tacrolimus, MMF, and steroids. Desensitization protocols were done with target 1/8 and negative CDC XM. The results:
Five of the 66 patients developed ABMR, accounting for 4% in non-sensitized patients and 18.8 in sensitized patients. Rebound DSA level increase in the sensitized group. More aggressive ABMR in the sensitized group with MFI above 5000 and they lost their graft 1 week after transplantation. Conclusion:
Despite the excellent one-year survival of ABOi transplantation, those with pre-transplant DSA with MFI above 5000 had poor outcomes even after desensitization. The presence of both barriers’ high sensitization and ABO incompatibility carry a poor prognosis and warrant searching for a more suitable solution i.e. paired exchange donation.
Esmat MD
2 years ago
This study is an observational prospective cohort study with level 2 of evidence that has evaluated and compared the kidney transplant outcomes in the ABO incompatible kidney transplant in the presence and absence of donor specific anti-HLA sensitization.
For expanding the donor pool, ABO-incompatible (ABO-I) renal transplantation is considered as an option.
Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of antibody- mediated rejection (AMR), and graft loss. Presence of both ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss. Development of new techniques such as gel card for ABO titer and, solid phase anti-HLA antibody assays to evaluate histocompatibility barriers, has improved our ability to assess and predict the risk of presence of ABOi, and HLA incompatibility. In addition, there has been great improvement in therapeutic options for management ABOi and HLA sensitization that reduce the risk of acute AMR.
An ABO or HLA incompatible organ desensitization protocols provides the basic mechanisms to modulate the immune system consists of Splenectomy and cytotoxic therapies such as rituximab and bortezomib for depleting the size of B and plasma cell clones. Removal of circulating antibodies is accomplished by procedures such as plasmapheresis or double filtration or immunoadsorption. IVIG may also directly inhibit the function of circulating antibodies.
In this study patients with ABOi were evaluate for HLA sensitization by CDC, flow PRA and SAB.
A positive flow crossmatch can pick up low level of DSA, which is missed
by CDC crossmatch. Both CDC and flow crossmatch assays should be done before transplant especially, in sensitized recipients and repeat transplants.
In SAB assay, each bead detects antibody directed against a single HLA antigen. Median fluorescence intensity (MFI) values of SAB assay semi-quantitatively estimate of the intensity of each anti-HLA antibody present. Multiplex bead antibody assay systems for anti-HLA antibodies use a solid phase platform consist of all of the most frequently observed HLA alleles (97 class I and 91 class II alleles).
DSA screening by lysate-based crossmatch assay identifies anti-HLA antibodies for class I and class II and their titer without capability to give the HLA specificities.
IgM ABO antibody titers are done by neutral gel cards and IgG ABO antibody titers are done using AHG gel cards. Anti- Blood group titer of 1:8 is the target. In this study, desensitization protocols were rituximab and plasmapheresis with the aim of decreasing isoagglutinin level below 1/8 before and within 2 weeks after kidney transplantation.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized group, ABMR was seen in 4.0% and in sensitized group ABMR was seen in 18.75% with DSA positivity. Graft loss within one month post-transplant was seen in 2 patients due to ABMR in the sensitized group with pretransplant positive DSA and in none in the non-sensitized group.
ABO incompatible renal transplantation has excellent one year graft and patient survival. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
This study concluded that Anti HLA DSA positivity with ABO-incompatibility is associated with poor graft survival.
Assafi Mohammed
2 years ago
Conclusion of the article:
Pre-operative anti-HLA DSA carries high risk for the development of ABMR and have inferior outcome regarding graft survival in ABOi transplantation despite of desensitization therapy. Patients with combined incompatibility(ABOi and HLAi) are better to be advised for swabbing or other alternatives than proceeding to transplant with this risky combined incompatibility even if desensitization therapy is used.
Study type : Observational prospective cohort study.
Level of evidence: type 2.
Balaji Kirushnan
2 years ago
The study is a prospective observational study with level of evidence being 2 conducted by SGPGI Lucknow India
ABOi and Anti HLA antibodies causing high DSA are both contraindicated for renal transplants due to the higher risk of ABMR….Ideally swap transplants, selection of blood group compatible donor or getting listed in deceased donor renal transplant program are the available options
66 patients who were for ABO incompatible renal transplants were evaluated for donor specific antibodies by SAB Luminex, CDD and Flow cytometry cross matches. Desensitization protocol was started 10 to 12 days before ABOi renal transplant and HLA i renal transplant…Patients were evaluated for ABMR, donor specific HLA desensitization and graft survival with anti HLA DSA positivity. The results were analyzed after the participants were divided into non sensitized and sensitized group…In non sensitized group ABMR was seen in 4 percent while in the sensitized group ABMR was seen in 18.5%..2 patients had graft loss within 2 months after transplant and these patients had pre transplant high DSA SAB MFI >5000. After desensitization the patients were taken up for surgery….This study quoted a patient and graft survival of 91.4% ad 90% after 4 years of ABOi surgery
Based on the above results they have concluded that anti HLA antibody with high MFI>5000 are associated with poor outcomes after ABOi renal transplants.
MICHAEL Farag
2 years ago
Association of ABO_I and specific anti DSA with MFI more than 5000 is considered a high risk transplantation even after desensitization and it is better to go for another option Level of the evidence is II
ahmed saleeh
2 years ago
Anti-HLA antibodies develop after exposure to foreign HLA antigens through blood transfusions, pregnancies and previous transplants
New technique to evaluate the histocompatibility barriers as antiHLA antibodies and ABO antibodies titers (gel card for ABO titer and, solid phase anti-HLA antibody assays) have improved our ability to regulate the risk of rejection in the presence of ABO and histocompatibility barriers.
ABOincompatible renal transplantation has excellent one year graft and patient survival. But patients going for ABO-I transplant who had single antigen bead assay (SAB)– HLA-DSA positivity with mean uorescence intensity (MFI) strength above 5000 did poorly despite desensitization. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss. HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation.
ABO i kidney transplant shows excellent one year patient and graft survival while patients with HLA DSA positive and ABO i are associated with poor graft survival especially with MFI strength above 5000 by SAB.
Preoperative Desensitization in ABO i transplant can reduce theses antibodies but they rebound after transplant and can cause ABMR
. Desensitization preoperatively, in ABO-I transplants can reduce anti-HLA antibodies also to acceptable levels, but these antibodies can rebound post-operatively and cause ABMR with graft loss.
Abdullah Raoof
2 years ago
1- Summarise the conclusion of this article.
Anti-HLA ab appear if patient expose to graft, pregnancy, blood transfusion.
While anti ABO Ab, is part of innate immunity it is present from fetal development period.
Patient with ABOi transplant who has Ab against HLA with high titer are at high risk of ABMR and graft loss.
ABOi transplantation was used to increase the donor pool.
Presence of these immunological incompatibilities make patient at high risk of hyper acute rejection , acute rejection, and graft loss.
Result
n-66 group A n= 50 (non-sensitize) group B n=16 (sensitized)
Graft survival at 1 month 100% 87.5%
Graft loss at 1 month 0% 12.5%
ABMR 4% 18.7%
No ABMR 96% 81.2%
Conclusion
Graft outcome is better when there is no any immunological incompatibility . With the presence of any immunological barrier the outcome worsen.
Degree of HLA incompatibility which is assessed by the presence and the level of anti HLA Ab.
ABOi also has its own risk carry bad prognostic outcome.
But patient who had high MFI Anti HLA Ab above 5000 (by luminex SAB) and who underwent ABOi kidney transplantation usually has poor outcome.
This double incompatible kidney transplantation associated with high risk of ABMR and poor graft survival.
Paired kidney donation is a best choice in these patient , if it is available . in most country including my country this option is not available , then desensitization will be next option.
Although desensitization of these patient to reduce Anti HLA DSA and isoagglutinin(anti ABO Ab)and to make cross match negative is helpful to transplant these patient but these Ab may rebound and predispose to rejection.
======
2- What is the type of this study and the level of evidence?.
This study is a prospective study with level of evidence of II.
Ahmed Omran
3 years ago
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO-incompatible renal transplantation Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of antibody- mediated rejection (AMR), and graft loss. Presence of both ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss.
. Patient with anti HLA DSA positivity and ABO incompatibility is associated with poor graft survival especially if MFI strength was more than 5000 .Preoperative desensitization in ABO-I transplants can reduce anti-HLA antibodies also to acceptable levels, but these antibodies can rebound and cause ABMR with graft loss.
DSA at baseline has a more significant impact on graft survival than isoagglutinin in case of combination of ABOi and HLAi transplantation which is considered high-risk to be managed carefully, and patient should preferably go for swap transplantation.
Prospective study, level 2
Mohamed Essmat
3 years ago
This is a prospective Cohort study of level 2 evidence
66 dialysis patients were checked for HLA antibodies before ABO incompatible transplantation using the CDC , flow CCx, and single antigen bead assays , all were -ve .
Antibody titers for IgM ABO antibodies are determined using neutral gel cards on serially diluted patient serum while titers of IgG anti-ABO antibodies were determined using AHG gel cards. The goal is to have an anti-blood group titer of 1:8.
After each session of PTx + IVIg, the ABO titration was done before and after each session.
Protocol for immunosuppressive drugs;
The induction therapy for all ABO-i KT patients consisted of either Simulect (on days 0 and 4) or ATG induction in high-risk patients was given in a total dose of 3–4.5 mg/kg on three doses given startin on day zero .
Triple IS : FK , MMF , steroids which started 10 days before surgery and continues .
Anti-HLA DSA positive in conjunction with ABO incompatibility was associated with poor graft survival.
Esmat MD
3 years ago
This study is an observational prospective cohort study with level 2 of evidence that has evaluated and compared the kidney transplant outcomes in the ABO incompatible kidney transplant in the presence and absence of donor specific anti-HLA sensitization.
For expanding the donor pool, ABO-incompatible (ABO-I) renal transplantation is considered as an option.
Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of antibody- mediated rejection (AMR), and graft loss. Presence of both ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss. Development of new techniques such as gel card for ABO titer and, solid phase anti-HLA antibody assays to evaluate histocompatibility barriers, has improved our ability to assess and predict the risk of presence of ABOi, and HLA incompatibility. In addition, there has been great improvement in therapeutic options for management ABOi and HLA sensitization that reduce the risk of acute AMR.
An ABO or HLA incompatible organ desensitization protocols provides the basic mechanisms to modulate the immune system consists of Splenectomy and cytotoxic therapies such as rituximab and bortezomib for depleting the size of B and plasma cell clones. Removal of circulating antibodies is accomplished by procedures such as plasmapheresis or double filtration or immunoadsorption. IVIG may also directly inhibit the function of circulating antibodies.
In this study patients with ABOi were evaluate for HLA sensitization by CDC, flow PRA and SAB.
A positive flow crossmatch can pick up low level of DSA, which is missed
by CDC crossmatch. Both CDC and flow crossmatch assays should be done before transplant especially, in sensitized recipients and repeat transplants.
In SAB assay, each bead detects antibody directed against a single HLA antigen. Median fluorescence intensity (MFI) values of SAB assay semi-quantitatively estimate of the intensity of each anti-HLA antibody present. Multiplex bead antibody assay systems for anti-HLA antibodies use a solid phase platform consist of all of the most frequently observed HLA alleles (97 class I and 91 class II alleles).
DSA screening by lysate-based crossmatch assay identifies anti-HLA antibodies for class I and class II and their titer without capability to give the HLA specificities.
IgM ABO antibody titers are done by neutral gel cards and IgG ABO antibody titers are done using AHG gel cards. Anti- Blood group titer of 1:8 is the target. In this study, desensitization protocols were rituximab and plasmapheresis with the aim of decreasing isoagglutinin level below 1/8 before and within 2 weeks after kidney transplantation.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized group, ABMR was seen in 4.0% and in sensitized group ABMR was seen in 18.75% with DSA positivity. Graft loss within one month post-transplant was seen in 2 patients due to ABMR in the sensitized group with pretransplant positive DSA and in none in the non-sensitized group.
ABO incompatible renal transplantation has excellent one year graft and patient survival. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
This study concluded that Anti HLA DSA positivity with ABO-incompatibility is associated with poor graft survival.
Wee Leng Gan
3 years ago
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO- incompatible Renal Transplantation.
This is a prospective cohort single centre study in India with level II evidence. The objective of this research is to assess for antibody mediated rejection (ABMR), donor specific anti HLA sensitisation, graft survival with anti HLA DSA positivity in ABO-incompatible kidney transplant recipients upon 4 years follow up. A total of 66 end stage renal failure patients on dialysis were recruited. The mean age (34.56±11.13). 98.4% of the subjects received tacrolimus and 1.6% on cyclosporine as immunosuppressant. At the time of transplant 62.5% of subjects received Basiliximab and the remaining 37.5% received ATG as induction. CDC, flow crossmatch were negative for all subjects at the time of transplant. The donor-specific antibody with mean fluorescence intensity (MFI) of more than 1000 were present in two subjects; 3.0%, whereas 64 subjects had MFI less than 500; 97.0% on SAB assay. The outcomes are better in non-sensitised group with 100% graft survival and 0% graft loss at 1 month. ABMR was seen in 4.0% of subject. However, the sensitised group reported statistic significant graft loss due to ABMR in 3 subjects (8.75%) of which 2 subjects happened within one week post-transplant. Both these patients had SAB DSA positivity, with total MFI strength above 5000 before desensitisation. After desensitisation the MFI came down to less than 1000 at the time of transplant, but showed significant rebound after ABOi transplant resulting in severe ABMR and graft loss. Patient survival was 97% and graft survival was 95% at one year of follow up. At four years post transplantation patient survival was 91.6% and graft survival was 91.5%. In conclusion, ABO incompatible renal transplantation has excellent one year graft and patient survival except those with single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000. HLA and ABO incompatibility in combination has poor outcome in term of patient and graft survival despite desensitisation. Swap transplant provide alternative to overcome the immunological barrier.
Jamila Elamouri
3 years ago
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO-incompatible renal transplantation
ABO-incompatible kidney transplantation has excellent one-year graft and patient survival. Patient with anti HLA DSA positivity and ABO incompatibility in combination is associated with poor graft survival especially if MFI strength was more than 5000 by SAB. Desensitization preoperatively, in ABO-I transplants can reduce anti-HLA antibodies also to acceptable levels, but these antibodies can rebound post-operatively and cause ABMR with graft loss.
DSA at baseline has a more significant impact on graft survival (ABMR) than isoagglutinin in the case of combined ABOi and HLAi transplantation which is a high-risk situation that needs to be adjusted carefully, and the patient should preferably go for swap transplantation.
its prospective study, level 2
Theepa Mariamutu
3 years ago
ABO incompatible transplant recipients with anti-HLA antibodies have higher risk of AMR and graft loss.
The study conducted to assess the effect of donor specific anti HLA sensitization on ABOi KTR
66 patients underwent ABOi KT, out of which 16 patients were sensitized. AMR was seen in 5 out of 66 patients (7.5%). In the sensitized group, AMR was seen in 18.75% (3 out of 16), while it was seen in 4% (2 out of 50) of non-sensitized patients.
Graft loss was seen in 2 out of the 3 sensitized patients with AMR and both had MFI >5000 before desensitization. The overall patient and graft survival at 1 and 4 years was 97% and 95% and 91.6% and 91.5%.
The conclusions derived include:
ABOi transplants have excellent one-year patient and graft outcomes.
ABOi with anti HLA DSA positivity has poor graft outcomes, especially with baseline MFI > 5000.
Desensitization can reduce anti HLA antibodies, but there is increased risk of antibody rebound and consequent graft injury.
Patients with ABOi with anti HLA antibodies should be enrolled in a kidney paired donation transplant program.
What is the type of this study and the level of evidence?
This is a prospective cohort study.
Level of evidence: Level II
Last edited 3 years ago by Theepa Mariamutu
Dalia Eltahir
3 years ago
ABO incompatible increase the numbers of donor in renal transplantation and has very good outcome . But when it associated with DSA (MFI) more than 5000 despite desensitization this combination lead to very poor graft survival due to acute AMR . Desensitization in ABO-I transplants can reduce anti HLA antibodies at time of transplantation , after transplant antibodies can rebound and cause ABMR with graft loss. Also there are great risk of infection in such condition pair exchange is advisable .
What is the type of this study ?
Prospective cohort study .
the level of evidence?
Level 2
Ramy Elshahat
3 years ago
Donor specific anti HLA sensitization is associated with inferior short-term outcomes in ABO-incompatible renal transplantation
Sonia Mehrotra, Raj Kumar Sharma⁎, Kavita Vishwakarma, Narayan Prasad, Amit Gupta, Dharmendra S. Bhadauria, Anupama Kaul
ABOi kidney transplantation was a solution for 30% of cases that had donors but unfortunately ABO incompatible with the recipient
This was before absolute contraindication for kidney transplantation but it was overcome by desensitization protocols.
Desensitization protocol for ABOi is almost the same protocol of desensitization of anti HLA antibodies, so theoretically it may be cost beneficial to do a transplant against ABOi in HLA DSA patients to remove both kinds of antibodies
In this study, sixty-six patients were evaluated for donor-specific anti-HLA sensitization before they received ABO-incompatible kidney transplantation. Then the patients were divided to 2 groups group A 50 patients (non-sensitized) and group B 16 patients(sensitized)
Antibodies screening for each recipient was evaluated by complement-dependent cytotoxicity (CDC) crossmatch, flow cytometric crossmatch, single antigen bead assay (SAB) and lysate-based solid-phase crossmatch. Standard desensitization protocolwas started 10 to 12 days prior to kidney transplant for ABO-incompatible and anti-HLA incompatible transplants. A regimen of desensitization was modified according to anti the A/B IgG titer targeting level 1:8.
Patients were evaluated for antibody-mediated rejection (ABMR), donor-specific anti-HLA sensitization, and graft survival with anti-HLA DSA positivity in ABO-incompatible kidney transplant recipients.
Antibody-mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized group-A, ABMR was seen in 4.0%, and in the sensitized group (group B) ABMR was seen in 18.75% with DSA positivity.
Graft loss within one-month post-transplant was seen in 2 patients due to ABMR in group -B and non in group-A (p-value = 0.05). Both two were transplanted with CDC and flow CM negative after desensitization and had SAB DSA MFI strength came down to ≤1000 which means memory carries a very high risk of rejection even with acceptable parameters pretransplant.
In this study patient survival was 97% and graft survival was 95% at one year, at four years Patient survival was 91.6% and graft survival was 91.5% follow up period. Anti HLA DSA positivity with ABO- incompatibility is associated with poor graft survival even after successful desensitization.
level of evidence
its prospective cohort study but with a poor design especially the study group is numerically not matched with a control group
level of evidence 2
Ahmed Abd El Razek
3 years ago
Summarize the conclusion of this article:
ABO incompatible renal transplantation is a risky procedure but it is worthy in general and of good patient and graft survival about 97 % compared to deceased donor Tx.
Risk of acute ABMR increases with the presence of HLA incompatibility together, especially with high MFI exceeding 5000 even after desensitization due to rebound phenomenon after Tx.
Besides of risk of infections due to increased immunosuppression status of these patients.
The type of this study and the level of evidence:
Prospective Cohort Study
Level of evidence 2
CARLOS TADEU LEONIDIO
3 years ago
Summarise the conclusion of this article
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
What is the type of this study and the level of evidence?
This is a primary study prospective cohort – level 02 of evidence.
Thanks, Carlos Nice to see your contribution. I advise you to read the others’ contributions as well
amiri elaf
3 years ago
# Summarise the conclusion of this article
Summary:
# Exposure to foreign HLA antigens from blood transfusions, pregnancies and previous transplants can result in development of Anti HLA antibodies.
# Patients have both ABO incompatible and anti HLA DSA are at high risk of AMR and graft loss.
# ABO incompatible and positive cross match are contraindication to transplantation because the risk of hyper acute or acute AMR.
# New methods to evaluate anti HLA and ABO antibodies titers (gel card for ABO titer and, solid phase anti HLA antibody assays) and to remove or decrease it’s production by modulating the immuneresponse prior to transplantation to minimize the risk of rejection episodes.
Result:
** In this study 66 patients were evaluated for the DSA before they received ABO- I kidney transplantation and all of them evaluated by CDCXM, FCMXM, SAB and lysate based solid phase crossmatch.
** The desensitization protocol was started10 to 12 days prior kidney transplant for all patients.
** Patients were evaluated for ABMR, DSA and graft survival.
* ABMR was seen in 5 patients(7.5%).
* In non sensitized (group A) ABMR was seen in 4.0%.
*In sensitized (group B) ABMR was seen in 18.75% with positive DSA.
* Graft loss within one month posttransplant was seen in 2 patients due to ABMR in the sensitized group -B with pretransplant positive DSA and in none in the non-sensitized group-A (p value = 0.05).
*Both these 2 patients had FCXCM, SAB DSA and Lysate CM positivity, with total MFI strength by SAB more than 5000
*These 2 patients with CDC and FCXCM became negative after desensitization and MFI decrease to1000.
* At one year patient survival was 97% and graft survival was 95%.
*At four years patient survival was 91.6% and graft survival was 91.5%.
*Positive DSA with ABO- I is associated with poor graft survival.
# Conclusion
*ABO incompatible renal transplantation has excellent one year graft and patient outcomes.
* ABO-I with positive HLA-DSA (MFI) more than 5000 by SAB assay has poor outcomes despite desensitization.
* Preoperative desensitization in ABO-I can reduce anti HLA DSA, but it can rebound after transplant and cause ABMR with graft loss.
* Anti HLA antibodies and ABO- I in combination is at high immunological risk situation, so better to go for paired exchange kidney donation.
# What is the type of this study and the level of evidence?
Prospective Cohort Study
Level of evidence 2
◇Donor specific anti HLA sensitization is associated with inferior short term
outcome in ABO- incompatible renal transplantation
¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤
☆Introduction:
________________
▪︎An ABO or HLA incompatible organ desensitization protocols provides the basic mechanisms to modulate the immune system as splenectomy and cytotoxic therapies such as rituximab and bortezomib decrease the size of B and plasma cell clones.
▪︎Physical removal of circulating antibodies is accomplished by plasmapheresis, double filtration or immunoadsorption.
▪︎IVIG may also directly inhibit the function of circulating antibodies.
☆ Materials and methods:
_____________________________
▪︎Sixty six patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation.
▪︎ Each recipient was evaluated by complement dependent cytotoxicity (CDC)
crossmatch, flow cytometric crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch .
▪︎The desensitization protocol was started10 to 12 days prior kidney transplant for ABO incompatible and anti HLA incompatible transplants.
▪︎ Patients were evaluated for antibody mediated rejection (ABMR), donor specific anti HLA sensitization, graft survival with anti HLA DSA positivity in ABO-incompatible
kidney transplant recipients.
☆ Results:
___________________________
▪︎Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients.
▪︎In non-sensitized group-A, ABMR was seen in 4.0% and in sensitized group (group-B) ABMR was seen in 18.75% with DSA positivity.
▪︎ Graft loss within one month post-transplant was seen in 2 patients due to ABMR in the sensitized group -B with pretransplant positive DSA and in none in the non-sensitized group-A (p value = 0.05). Both these two patients sensitized group -B had flow CM, SAB DSA and Lysate CM positivity, with total MFI strength by SAB was above 5000, these two patients with CDC and flow CM negative after desensitization and had SAB DSA MFI strength came down to ≤1000.
▪︎In this study patient survival was 97% and graft survival was 95% at one year, at four
years patient survival was 91.6% and graft survival was 91.5% follow up period.
▪︎ Anti HLA DSA positivity with ABO- incompatibility is associated with poor graft survival.
☆Conclusion:
_______________
▪︎One year graft and patient survival in ABO incompatible renal transplantation is excellent . But patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean
fluorescence intensity (MFI) strength above 5000 did poorly despite desensitization.
▪︎Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB
assay.
▪︎ Desensitization in ABO-I transplants can reduce anti HLA Abs also to acceptable levels but the anti-HLA Abs can rebound after transplant and cause ABMR with graft loss.
▪︎It is preferable to go for swap transplantation in combined HLA and ABO incompatibility.
● Type of the study: prospective cohort
●Level of evidence: II
66 patients with end stage of kidney failure (92.2% male, 7.8% female) on dialysis their age mean (34.56 ± 11.13), were evaluated prospectively before ABO incompatible kidney transplantation.
Patients were evaluated for donor specific anti HLA sensitization by complement dependent cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch. Gel card method was used to measure anti ABO titers. AntiBlood group titer of 1:8 is the target. The ABO titration was performed before and after every session of PP/ IVIg.
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which is administered, 10 to 12 days prior to kidney transplant (KT). 2 to 10 sessions of plasmapheresis (anti- ABO titer) performed over 2 to 14 days before surgery until a recipient’s isoagglutinin titer decreased to a level below 1:8. Postoperative plasmapheresis was given if the anti-A,B isoagglutinin titer increased significantly above a level of 1:8 (within first two weeks of transplant) associated with graft dysfunction with allograft biopsy suggestive of ABMR.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized, group-A (n = 50, MFI ≤1000 on SAB assay) ABMR was seen in 4.0% of patients. In sensitized, group-B (n = 16, MFI≥1000), ABMR was seen in 18.75% of patients, with rebound of DSA positivity. Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in the sensitized group -B (p value = 0.05). Both these patients had SAB DSA positivity, with total MFI strength above 5000 before desensitization. After desensitization the MFI came down to ≤ 1000 at the time of transplant, but showed significant rebound after ABOi transplant resulting in severe ABMR and graft loss. Suggesting that patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000 did poorly despite desensitization. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
Patient survival was 97% and graft survival was 95% at one year and at four years Patient survival was 91.6% and graft survival was 91.5%.
HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation.
This is a prospective cohort study. so it’s level of evidence is II.
conclusion:
Althoug ABOi transplantation have excellent 1 year graft survival the higher MFI (more than 5000) the worse the prognosis. Ther rebound of DSAs is expected . The worst prosnosisi is in case of combined HLA and ABO incompatibility. In such case, paired exchange is worth.
Outcome of HLA sensitized patient comparing non-sensitized ABO incompatible kidney transplantation were evaluated in 66 patients. Five patients had ABMR, 4% in non-sensitized and 18.75% in sensitized patient and two graft loss was seen only in sensitized group. They concluded that HLA incompatible TX in context of ABOi-KT, is associated with poor graft survival. This is true especially if MFI was more than 5000. Because even after desensitization, DSA could rebound after TX and resulted in ABMR or even graft loss. So in this situation, choosing another options such as KPD is reasonable. This is a prospective cohort study with level of evidence 2.
Introduction
Anti-HLA antibodies develop after exposure to foreign HLA antigens
through blood transfusions, pregnancies and previous transplants.
Patients of ABO incompatible transplants who have antibody against
their donor HLA antigens with high strength are at high risk of antibody-
mediated rejection (AMR), and graft loss.
Materials and methods
Patient selection
Patients were evaluated for donor specifc anti HLA sensitization
before they received ABO incompatible kidney transplantation. Each
recipient was evaluated for anti-HLA sensitization by complement dependent
cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen
bead assay (SAB) and lysate based solid phase crossmatch.
Flow cross match serves as a sensitive cross match test for the detection
of DSA
The solid phase assays like (single antigen bead assay) SAB, detect
anti-HLA antibodies against the donor. Single antigen bead (SAB) assays
have increased sensitivity and specificity of detecting anti-HLA
antibodies results. A limitation of solid phase assays is that the beads could be coated with HLA molecule which could get altered during recombinant processing
Gel card method was used to measure anti ABO titers. Anti- Blood group titer of 1:8 is the target.
Desensittzation protocol with Rituximab , aphresis therapy preoperatively until isoagglutinin titre is less than 1:8 , postop aphresis is applied if the anti-A,B isoagglutinin
titer increased significantly above a level of 1:8 (within first two weeks
of transplant) associated with graft dysfunction with allograft biopsy
suggestive of ABMR.
On 66 studied patients , Antibody mediated rejection (ABMR) was seen in five (7.5%) patients. In non-sensitized, group-A (n = 50, MFI <1000 on SABassay) ABMR was seen in 4.0% of patients. In sensitized, group-B (n = 16, MFI>1000), ABMR was seen in 18.75% of patients, with rebound of DSA positivity. Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in
the sensitized group -B (p value = 0.05). Both these patients had SAB
DSA positivity, with total MFI strength above 5000 before desensitization.
After desensitization the MFI came down to ! 1000 at the time
of transplant, but showed signi!cant rebound after ABOi transplant
resulting in severe ABMR and graft loss
Discussion
Results shows that patients who were going for ABO-I transplant
who had anti-HLA antibodies before desensitization had increased
ABMR. Desensitization protocols effectively result in successful ABO-I
renal transplantation, but there is increased ABMR and graft loss in
sensitized patients with anti-HLA antibodies (DSA).
Although various desensitization strategies are attempted to overcome immunologic barriers to transplantation , however , there are still problems of de novo Abs and the rebound of Abs ( especially in those with high Ab level before desensitization )
Chung BH et al suggested that HLAi is more determining for the incidence of acute ABMR than ABOi . Loupy et al. and Amico et al. have reported that preformed DSA
antibodies correlate with a high incidence of subclinical AMR
both late rejections and resistance to treatment are strongly
associated with class II DSA, especially HLA-DQ, antibody
CONCLUSION
ABO incompatible renal transplantation has excellent one year graft
and patient survival. But patients going for ABO-I transplant who had
single antigen bead assay (SAB) – HLA-DSA positivity with MFI strength above 5000 did poorly despite desensitization. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies
can rebound after transplant and cause ABMR with graft loss
This report is concerned with anti HLA sensitization specifically for the donor and how this process may not have the expected outcomes but instead have poor short term outcome for ABOi kidney transplant.
In ABOi transplant, presence of HLA antibodies before desensitization is linked with ABMR. Desensitization results in successful ABOi transplants. Sensitized patients have increased risk of ABMR and graft loss.
De novo antibodies can lead to ABMR. Patients undergoing combined ABOi and HLAi kidney transplants have similar risk of ABMR as patients undergoing HLAi kidney transplant.
AMR impacts long term outcome of kidney transplant. DSA MFI does not correlate the chronicity or severity if AMR. Both late rejection and resistance to treatment are strongly linked with class II DSA, especially HLA DQ antibody.
ABOi renal transplant has been seen to have good one year outcome in terms of graft and patient survival. But patients undergoing ABOi transplant with HLA DSA positive and MFI above 5000 had poor outcome post transplant despite desensitization.
Preoperative desensitization in ABOi kidney transplant can reduce anti HLA antibodies to acceptable levels but rebound post transplant is possible, and this can cause ABMR and graft loss. In the case of combined HLAi and ABOi transplant, it is dangerous in terms of immunology and it is better for the patient to go for swap transplantation.
Type of study
Prospective cohort study
Level of evidence II
Prospective cohort observational study with level II .
This study shows that ABO-I kidney transplant patients with anti HLA- antibodies have more chance to develop ABMR although ABO-I transplant has excellent one year patient and graft survival,patients with MFI >5000and ABO-I have poor outcome even when desensitization protocols have been done.
Desensitization protocol can affect on anti HLA-Antibodies causing it to reduce to acceptable level but there will be rebound antibodies leading to ABMR and graft loss.
So the main message of this study is ABO-I with HLA (especially high titer)can put the patient in high immunological risk.
ABO incompatible kidney transplantation increase the donor pool with good patient and graft survival.
Presence of anti-HLA DSA especially with MFI> 5000 negatively affect the graft survival despite desensitization.
Kidney transplantation in presence of ABO incompatibility and DSA positivity is associated with higher immunological risk
Preoperative desensitization decreases DSA to acceptable levels before transplantation but with risk of antibody rebound post transplant which may lead to AMR and graft loss.
Kidney exchange programs are better alternative for patients with ABO incompatibility and DSA positivity due to the associated high immunological risk
What is the type of this study and the level of evidence?
Prospective study
level of evidence: 2
Mohamad Habli
3 years ago
Anti-HLA DSA and ABO incompatibility and positive has been considered a contraindication to transplantation. Sensitized patients due to anti-HLA DSA and ABO incompatibility are at higher risk of graft loss. The presence of blood group isoagglutunins is associated with significant risk of hyper acute or acute AMR.However, the development of desensitization protocols in ABOi and patients with preformed DSA has increased the donor pool.
66 patients with ESRD were included in this prospective study. The aim is to evaluate patient and graft survival in ABOi kidey transplantation in the presence of preformed anti-HLA DSA.
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab, plasmapheresis followed by IVIg (dose – 100 mg/kg per PP session) , until a recipient’s isoagglutinin titer decreased to a level below 1:8.
Induction therapy was either Basiliximab or r-ATG followed by maintenance therapy that included MMF, tacrolimus and steroids.
CDC and flowcytometry crossmatch were negative at time of surgery. DSA MFI were < 1000 after desensitization protocols , except in 2 patients.
Results
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients.
In non-sensitized, group-A ABMR was seen in 4.0% of patients.
In sensitized, group-B, ABMR was seen in 18.75% of patients.
Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in the sensitized group –B.
In conclsion, patients who were going for ABO-I transplant who had anti-HLA antibodies before desensitization had increased ABMR. Patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000 had poor graft survival despite desensitization.
In ABO-incompatible kidney transplantation, donor-specific anti-HLA sensitization is linked with a worse short-term prognosis than incompatible transplantation.
In this prospective research, 66 dialysis patients were screened for HLA antibodies before to ABOi transplantation using the CDC, flow cross-match, and single antigen bead assays, all of which were negative.
Testing for antibodies;
Luminex-based solid-phase tests, as compared with conventional CDC and flow crossmatch findings, require HLA labs to establish cut off (MFI) values for significance in order to standardize results across laboratories.
The anti-ABO titers were determined using the gel card technique.
Antibody titers for IgM ABO antibodies are determined using neutral gel cards on serially diluted patient serum.
Titers of IgG anti-ABO antibodies were determined using AHG gel cards. The goal is to have an anti-blood group titer of 1:8.
After each session of PP/IVIg, the ABO titration was done before and after each session.
Protocol for immunosuppressive drugs;
The induction therapy for all ABO-i KT patients consisted of either Basiliximab (an anti-CD25 monoclonal antibody) (on days 0 and 4) or Rabbit anti-thymocyte globulin (ATG) induction in high-risk patients was given in a total dose of 3–4.5 mg/kg on three doses given on days zero and then alternate days post-transplant.
The patients were given triple sequential immunosuppression, including mycophenolate mofetil (MMF; dose – 1500–2000 mg/day) and tacrolimus (dose – 0.1 mg/kg daily; adjusted to a 12 h, trough levels of 8–12 ng/ml), as well as low-dose steroids, which were started 10 days before surgery and continued for the duration of the study.
Anti-HLA DSA positive in conjunction with ABO incompatibility is linked with poor graft survival, particularly during the immunological evolution phase if the MFI strength measured by the SAB test was more than 5000, according to the study.
This is a prospective cohort study non-experimental observational study
Level 2
66 patients with end stage of kidney failure were evaluated prospectively before renal transplantation.
Patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation.
The patients demographics were :
Age
Patient Sex:Male
Patient Sex:Female
Weight
Height
duration of dialysis
HLA Mismatch
Immunosuppression
Tacrolimus
Cyclosporin
Induction
ATG
Basiliximab
CDC crossmatch
Flow crossmatch
donor-speci!c antibody (DSA) 1000 donor-speci!c antibody (DSA) <1000 age of donor
Donor Sex:Male
Donor Sex:Female
GFR donor
Each recipient was evaluated for anti-HLA sensitization by complement dependent cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch.
Gel card method was used to measure anti ABO titers.
The patients divided into 2 groups
group A(non-sensitized)
group B(sensitized)
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which is administered, 10 to 12 days prior to kidney transplant.
2 to 10 sessions of plasmapheresis were given performed over 2 to 14 days before surgery until a recipient's isoagglutinin titer decreased to a level below 1:8.
Postoperative plasmapheresis was given if the anti-A,B isoagglutinin titer increased signi!cantly above a level of 1:8 (within !rst two weeks of transplant) associated with graft dysfunction with allograft biopsy suggestive of ABMR.
induction therapy include basiliximab and ATG
The patients received triple sequential immunosuppression – mycophenolate mofetil (MMF; dose – 1500–2000 mg/day) and tacrolimus (dose – 0.1 mg/kg daily; adjusted to a 12 h, trough levels of 8–12 ng/ ml) and low dose steroids prednisolone were started 10 days prior to surgery.
The patients and graft survival outcome were studied at one and four year.
Results:
CDC,flow crossmatch were negative for all pa- tients at the time of transplant but donor-speci!c antibody mean fluorescence intensity (MFI) 1000 were present in two patients (3.0%).In rest 64 patients MFI was <500 (97.0%) on SAB assay.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized, group-A (n = 50, MFI <=1000 on SAB
assay) ABMR was seen in 4.0% of patients. In sensitized, group-B (n = 16, MFI1000), ABMR was seen in 18.75% of patients, with rebound of DSA positivity.
Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in the sensitized group -B .Both these patients had SAB DSA positivity, with total MFI strength above 5000 before desensitization.
Patient survival was 97% and graft survival was 95% at one year and at four years Patient survival was 91.6% and graft survival was 91.5%.
This study shows that patients who were going for ABO-I transplant who had anti-HLA antibodies before desensitization had increased ABMR. Desensitization protocols e#ectively result in successful ABO-I renal transplantation, but there is increased ABMR and graft loss in sensitized patients with anti-HLA antibodies (DSA).
In Conclusion:
ABO incompatible renal transplantation has excellent one year graft and patient survival. But patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000 did poorly despite desensitization. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss. HLA and ABO incompatibility in combination is a high risk situation from im- munological point of view. In such a situation patient should preferably go for swap transplantation.
Anti-HLA antibodies develop after exposure to foreign HLA antigens through
blood transfusions
pregnancies and
previous transplants.
As reported previously Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of anti- body-mediated rejection (AMR), and graft loss . To address this issue this study was conducted to confirm that Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO- incompatible renal transplantation.
Patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation. Each recipient was evaluated for anti-HLA sensitization by complement dependent cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch.
The desensitization protocol for ABO incompatible transplant included infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which was administered, 10 to 12 days prior to kidney transplant (KT). 2 to 10 sessions of plasmapheresis were given (depending on the
anti- ABO titer) performed over 2 to 14 days before surgery until a recipient’s isoagglutinin titer decreased to a level below 1:8.
Induction was either with basiliximab or ATG.
66 patients underwent ABO incompatible kidney transplant, out of which 16 patients were sensitized. AMR was seen in 5 out of 66 patients (7.5%). In the sensitized group, AMR was seen in 18.75% (3 out of 16), while it was seen in 4% (2 out of 50) of non-sensitized patients.
Graft loss was seen in 2 out of the 3 sensitized patients with AMR and both had MFI >5000 before desensitization. The overall patient and graft survival at 1 and 4 years was 97% and 95% and 91.6% and 91.5%.
Conclusion
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
. HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation
since succeed to overcome the barriers of ABO incompatible and positive cross match which has been considered as contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss via therapeutic options of desensitization protocols.
1. Removal of circulating antibodies via plasmapheresis, or immunoadsorption and decrease production of anti-AB and anti-HLA antibodies.
2. The supplementary immunosuppressive medications as well as IVIG via Fc receptor signaling pathways impair the ability of cells to make antibodies.
Aiming to reduce the risk of rejection through immune modulation pre transplant
Cohort study was conducted; sixty-six patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation. (CDC, flow cytometry cross match, (SAB) and lysate based solid phase cross match). The desensitization protocol was started10 to 12 days’ prior kidney transplant for ABO incompatible and anti HLA incompatible transplants at our center. Patients were evaluated for antibody mediated rejection (ABMR), donor specific anti HLA sensitization, graft survival with anti HLA DSA positivity in ABO-incompatible kidney transplant recipients.
Conclusion
1. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
2. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
3. HLA and ABO incompatibility in combination is a high risk situation from immunological point of view.
4. In such a situation patient should preferably go for swap transplantation. What is the type of this study and the level of evidence? Prospective Cohort study. Level of evidence -II
ABOi transplantation has an excellent one year graft and patient survival.
patients who have HLA-DSA of MFI > 5000 and ABOi did poorly despite desensitization.
ABOi + DSA> 5000 is associated with poor graft survival.
desensitization for ABOi can also reduce Anti-HLA antibodies to an acceptable level, but there is a risk of rebound and ABMR with graft loss.
ABOi + HLAi is a high-risk situation from an immunological point of view.
What is the type of this study and the level of evidence?
Prospective cohort study
Level of evidence: II
Wael Jebur
3 years ago
This is a prospective study involved 66 patients who undergone ABOi transplantation after desensitization protocol aiming at antibody titer of less than 1/8, Meanwhile pretransplant HLA assessment revealed 16 patients sensitized with SAB of more than 1000 MFI. AMR was reported in 3/16 patients in sensitized group and in 2/50 patients in non sensitized group, Rebound of DSAs was noticed and correlated with incidence of AMR. There was no rebound of AB antibodies
This study concluded that there is an increased incidence of AMR for patients who undergone ABOi transplant who are concurrently HLA incompatible.
I believe the result is not consistent and non related to anti ABOi transplantation, as the incidence of AMR is directly and conclusively related to rebound of DSAs or emergence of De novo HLA antibodies and there was no correlation to Anti B, A antibodies titer which was entirely maintained within the pre transplant titer with no rebound, refuting any link to the AMR. Furthermore the size of sample was small.
The study is prospective with level of evidence of 1
· Summarise the conclusion of this article:
Anti HLA antibodies can develop due to exposure to HLA antigens resulting from previous blood transfusions, pregnancy, and previous transplants. ABOi and positive crossmatch is a contraindication to transplantation due to the high risk of hyperacute rejection and acute AMR. Recipients with ESRD who are planned for ABOi-KT were evaluated for pre-formed Anti HLA antibodies. Donor-specific anti-HLA sensitization is associated with inferior short-term outcome in ABO-incompatible renal transplantation. · ABOi-KT has increased the potential donor pool. · Desensitization protocol modulates the immune system aiming to reduce antibodies titers (ABO&HLA) and to reduce the risk of ABMR posttransplant. ABO-incompatible renal transplantation has excellent one year graft and patient survival. · Patients going for ABO-I transplant who had DSA with MFI > 5000 did poorly despite desensitization and is associated with poor graft survival · Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss. · HLA and ABO incompatibility in combination is an immunologically high risk. And preferred to go for paired exchange transplant.
What is the type of this study and the level of evidence? Prospective Cohort study. Level of evidence -II
MOHAMMED GAFAR medi913911@gmail.com
3 years ago
ABOi transplantion is chalenging process, using aggresive stratiges and medical staff to acheive it
Transplanting patient with preperformed DSA aganist the recipent grfat is also chalenging but doable .
Combinning both is to some extent risky in terms of short and long term graft outcomes.
In this study 66 patient was evaluted befor ABOi transplantion with preperformed DSA aganist the grfat.
Using plex with IV IGg and RTX befor transplantion,for desentization was succeful to desrease the haemagltinin titre <1/8.
Induction was by simulect or ATG as the protocl .
Results showed inferior graft survival for patient with high MFI > 5000 DSA .
HLA and ABO incompatibility in combination is a high risk situation from im munological point of view, and pt showed be advised for PKD programm.
this is an obervational (prospective)studty with level of evidence 2
-ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has a signifcant risk of hyperacute or acute AMR and graft loss due to the presence of blood group antibodies or HLA antibodies in the recipient.
– Patients who have positive PRA or patients with persistent weakly positive cross matches may require therapy before transplant, lowing antibody titers (ABO and HLA) so that crossmatch becomes negative per transplant this reduces the risk of acute ABMR post-transplant especially in anti-HLA sensitized about transplant.
– 66 patients with end-stage kidney failure enrolled in study.
-Patients who were going for ABO-I transplant who had anti-HLA antibodies before desensitization had increased ABMR.
-Desensitization protocols effectively result in successful ABO-I renal transplantation, but there is increased ABMR and graft loss in
sensitized patients with anti-HLA antibodies (DSA).
– There could be a rebound of ant HLA DSA or anti-ABO antibody in high anti-ABO antibody producers which are difficult to desensitize.
-One study showed that KT in patients with combined ABOi and HLAi had a similar incidence of acute AMR to that in exclusively HLAi patients, and was inferior to that in ABOi patients or high baseline titer of anti-A/B antibody was no longer a significant predictor for acute AMR when the HLAi group was included, but a strong HLA-DSA at baseline was still a significant risk factor for acute AMR even when the ABOi group was included.
-Pre-transplant DSA is a risk factor for rejection, and preformed antibodies correlate with a high incidence of subclinical AMR and that pre-Tx DSA was associated with acute vascular and chronic rejection and poorer graft outcome.
-Acute AMR has a substantial impact on the long-term outcome and preoperative DSA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOi kidney transplantation.
-DSA MFI does not correlate with the chronicity and severity of pathology of AMR.
-Both late rejections and resistance to treatment are strongly associated with class II DSA, especially HLA-DQ, antibody.
-ABO-incompatible renal transplantation has an excellent one year graft
and patient survival.
– Patients going for ABO-I transplant who had SAB – HLA-DSA with MFI˃ 5000 did poorly despite desensitization.
-HLA and ABO incompatibility in combination patients should preferably go for swap transplantation.
_It is prospective study .
-Level II.
ABO incompatible transplant recipients with anti-HLA antibodies have higher risk of antibody mediated rejection (AMR) and graft loss. This study was conducted to assess the effect of donor specific anti HLA sensitization on ABO incompatible kidney transplant recipients. In this study, 66 patients underwent ABO incompatible kidney transplant, out of which 16 patients were sensitized. AMR was seen in 5 out of 66 patients (7.5%). In the sensitized group, AMR was seen in 18.75% (3 out of 16), while it was seen in 4% (2 out of 50) of non-sensitized patients. Graft loss was seen in 2 out of the 3 sensitized patients with AMR and both had MFI >5000 before desensitization. The overall patient and graft survival at 1 and 4 years was 97% and 95% and 91.6% and 91.5%.
The conclusions derived include:
a) ABO incompatible transplants have excellent one-year patient and graft outcomes.
b) ABO incompatibility with anti HLA DSA positivity has poor graft outcomes, especially with baseline MFI > 5000.
c) Desensitization can reduce anti HLA antibodies, but there is increased risk of antibody rebound and consequent graft injury.
d) Patients with ABO incompatibility with anti HLA antibodies should be enrolled in a kidney paired donation transplant program.
What is the type of this study and the level of evidence?
This is a prospective cohort study.
Level of evidence: Level II
*ABO incompatible and positive crossmatch barrier was considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss due to the presence of blood group antibodies (iso-agglutinins) or HLA antibodies in the recipient.
*This study was done on 66 recipients with positive DSA before transplantation and received ABOi-KT.
*They were evaluated by CDC crossmatch, FCXM, SAB.
*Different desensitization protocols were applied aiming to remove current Ab ,modulate immune response, deplete B cell and reduced Ab production mainly with rituximab, plasmapheresis, triple immunosuppression 10 days before transplantation and IVIg
with induction with basiliximab or ATG.
*RESULTS
– ABO-I recipients who had anti-HLA antibodies MFI strength above 5000 did poorly despite desensitization with increased ABMR.
-Desensitization protocols allowed successful ABO-I renal transplantation, but there is increased ABMR and graft loss in sensitized patients with DSA.
-AMR could be due to either de novo antibody, (either anti-ABO antibody or HLA antibody) or
rebound of ant HLA DSA or anti ABO antibody.
– KT in patients with combined ABOi and HLAi had a similar incidence of acute AMR to that in exclusively HLAi patients, and was inferior to that in ABOi patients.
– a strong HLA-DSA at baseline was still a signifcant risk factor for acute AMR even when the ABOi group was included .
-preoperative DSA have signifcant association with poor graft outcomes than anti-blood group antibodies, even in ABOi kidney transplantation.
-ABO incompatible renal transplantation has excellent one year graft and patient survival.
Therefore HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for paired kidney exchange programme
This is Prospective study with control group, level of evidence II
Q1. Summary Rationale for ABO-incompatible kidney transplantation:
o Potentially increase the donor pool.
o Advancement in immune suppression and techniques that deplete anti HLA antibodies or prevent their further production (desensitization).
o Newer Immunosuppression that decrease risk of rejection. Prerequisites for HLA i transplantation:
o Done till obtaining negative CDC cross match prior to transplant.
Materials and methods:
Patients were evaluated for DSA by CDC crossmatch, FCXM, Luminex SAB and lysate based solid phase crossmatch. Desensitization protocol: Rituximab 500 mg (RTX; dose – 375/mg/ m2) given, 10 to 12 days prior to transplant. PEX, 2 to 10 sessions of were given. Recipient’s isoagglutinin titer
decreased below 1:8. Followed by low dose IVIG (100 mg/kg /dose) (after each PP session). Postoperative PEX only if the anti-A, B isoagglutinin titer increased significantly above a level of 1:8 (within first two weeks of transplant) associated with
graft dysfunction with allograft biopsy suggestive of ABMR. Induction: All the ABO-i KT patients received Basiliximab Or ATG if high-risk patients. Maintenance: triple tacrolimus-based immunosuppression with MMF and prednisolone. Discussion and summary:
o ABO-I transplant in those who had anti-HLA antibodies before desensitization had increased risk of ABMR, especially if MFI strength was more than 5000 by SAB assay.
o ABOi plus anti-HLA DSA positive represents a double hit and better to be avoided. Even with effective desensitization protocols, it still carries a high risk of rejection and graft loss.
o Best for highly sensitized recipients is KPD with much reduced cost. Limitation: small sample size with short follow up Q2 What is the type of the study and level of evidence? Prospective cohort with control group, level II
Thanks dear professor for your effort and continuous encouragement.
kumar avijeet
3 years ago
ABOi transplant increases the donor pool, but ABOi along with HLAi with preformed DSA is a very complex and very high risk transplantation from immunological point of view.
1.ABOi tx has good graft and patient survival.
2.ABOi tx with HLAi with DSA having mfi >5000 have poor graft and patient survival, even after desensitization process pre tx to lower down the mfi value is basically due to rebound of anti-HLA ab after tx leading to abmr and graft loss and due to high desensitization patient survival decreases to other morbidities.
Hence before overcoming dual immunological barrier, it is better to undergo kidney paired donation if feasible.
Donor specific anti HLA sensitization is associated with inferior short-term outcome in ABO- incompatible renal transplantation Summarise the conclusion of this article:
This prospective cohort study included 66 cases with ABOi kidney transplant recipient with median age 34 and majority males 97%, induction with basiliximab in 62.5% of cases while ATG given in 37.5%
Majority received tacrolimus based conventional immunotherapy 98.4% only one case received cyclosporine based with MMF and prednisolone
All have negative crossmatch by CDC and FXCM, Luminex based solid phase assay for DSA with MFI cutoff value of 1000
Gel card method used for anti ABO titer measurements; IgM ABO ab titer done by neutral gel card while IgG ABO titer done by using AHG gel card with target level for transplantation of 1:8
Desensitization protocol of rituximab 375mg / m2 10-12 days, plasmapheresis 2-10 sessions alternate day with low dose IVIG 100mg/KG There is higher rate of graft loss and ABMR in the sensitized group 12.4 and 18.6 respectively in the first month post-transplant, the DSA rebound risk was higher in those with higher MFI prior to desensitization. Conclusion of this study:
1- ABOi kidney transplant alone help in expanding the donor pool and favor one year graft and patient survival.
2- ABOi KTX plus anti-HLA DSA positive double hit better to be avoided even with desensitization carry high risk of rejection and graft loss.
3- In ABOi ktx the Pre transplant desensitization will reduce the anti HLA abs to the acceptable level but associated with high risk of early rebound after transplantation and AMR so better to avoid such combination and allocate for KPD program will be safer and less cost
Limitation: small sample size with short follow up What is the type of this study and the level of evidence?
Prospective cohort with control group, level 2
You are the first one who notices the limitations of this study. Very impressed
Hinda Hassan
3 years ago
Summarise the conclusion of this article
This study included 66 patients who received ABO incompatible kidney transplantation who received desensitization protocol 10 to 12 days prior kidney transplant. Most of them were males (92.2% male, 7.8%female). CDC were negative for all patients at the time of transplant. ABMR
patients undergoing ABO-I transplant who had anti-HLA antibodies before desensitization had high risk of ABMR. ABMR was seen in 7.5% of all patients. Non-sensitized group with MFI< 1000,ABMR was seen in 4.0% and in sensitized group MFI> 1000, ABMR was seen in 18.75% . Graft loss within one month post-transplant
There is increased risk of graft loss in sensitized patients with DSA undergoing ABO-I transplant.
This was seen only in 2 patients due to ABMR in the sensitized group ( Both these patients had MFI > 5000 before desensitization which dropped to < 1000 at the time of transplant, but showed significant rebound after transplant) Patient and graft survival
At one year patient survival was 97% and graft survival was 95%. At four yearspatient survival was 91.6% and graft survival was 91.5%.
So despite the fact that ABOi renal transplantation has excellent one year graft and patient survival, those with MFI >5000 have poor outcome. The combination of DSA positivity and ABO- incompatibility is associated with poor graft survival especially if MFI is > 5000 by SAB. Furthermore , there is a risk of rebound of anti-HLA antibodies after desensitization.
What is the type of this study and the level of evidence?
This is a single centre cohort study. It is not clear whether it is retrospective or prospective, so it could be level 2 or 3.
ABOi transplantation associated with very good patient & graft outcome at 1year post transplant.
ABOi transplantation with positive DSA & MFI> 5000 had poor outcome ( patient & graft) even with desensitization.
ABOi transplantation with positive DSA ( MFI>5000) who had preoperative desensitization was associated with rebound of anti-HLA antibodies & high risk of ABMR & subsequent graft loss.
Combined ABOi & HLAi transplantation considered as high immunological risk transplant, & better to find more suitable donor through PKD program.
summary of the article:
exposure of recipient to blood transfusion, previous transplant and pregnancy result in anti-HLA bodies formation .
there are two barrier for renal transplantation: ABO incompatibility and HLA incompatibility.
ABO i has potential increase the donor pool.
ABO i and positive cross match contraindicated as high risk for hyper acute or acute AMR and graft loss.
desensitization protocol modulate immune system as to lowering antibodies titre (ABO&HLA) to keep cross match negative pre transplant to reduce risk of ABMR pos
transplant.
new technique to evaluate histocompitability and anti HLA antibodies and ABO titre such as gel card for antibodies titre and rejection in solid phase anti HLA anti body assays improved and regulate the risk of rejection in presence of ABO and histocompatibilty.
in this study paients were evaluate for donor specific anti -HLA sensation by CDC crossmatch,flow crossmatch,SAB as to measure anti ABO and lysate based solid phase crossmatch and ABO i kidney transplant using gel card method to measure anti ABO titre keep the target 1:8 .
desensitisation protocol:
for ABOi transplant,rituximab,plasmapharsis followed by:
basilixmab, ATG( induction) and triple immunosupression thearpy
HLAi group has significance risk factor for acute AMR and and poor graft survival for acute AMR than ABO i.
Class 11 DSA antibodies espcillay HLADQ antibody associated with late rejection and resistance to treatment. conclusion
ABOi renal transplant has excellent one year graft survival.
ABOi transplant and HLA DSA postive >500 has poor out come even with desensitization protocol .
rebound antiHLA antibodies even after desensitization which can cause ABMR with graft loss.
prospective cohort study.
level 11 evidence.
Patients of ESRD who are planned for ABO incompatible renal transplantation were evaluated for pre formed Anti HLA antibodies
Each such recipient was evaluated comprehensively for the presence of anti-HLA antibodies by the combination of CDC crossmatch, Flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch
A total of 66 patients were included in the study and were stratified into two groups – Group A contained Non Sensitised patients (N=50) and Group B contained the sensitised recipients (N=16)
The desensitisation protocol consisted of Rituximab and Plasmapheresis. Isoagglutinin titer decreased to a level below 1:8 was taken as an end point to accept for ABOi Transplantation
In Non- Sensitized group A (with MFI <1000), ABMR was seen in 4.0% of patients.
In contrary, in Sensitized group B ( MFI>1000), ABMR was seen in 18.75% of patients
Further, only in Sensitised patients group, rebound DSA were noted. Such rebound in DSA was severe enough to culminate in Graft loss in two patients. Both those patients had DSA titers of > 5000 MFI prior to desensitisation ( And had been demonstrated to have MFI < 1000 after sensitisation)
Graft Survival at one year was 100 % in Group A while it was 87.5 % in Group B.
Though ABO incompatible Transplantation had excellent one year survival , patients going for ABO-i transplant who had preformed DSA of MFI > 5000 did poorly despite desensitization
Anti HLA DSA positivity on the back drop of ABO- incompatibility is associated with poor graft survival especially if the titer of Anti HLA antibodies happens to be above 5000 MFI prior to the desensitisation therapy
ABO incompatibility and HLA incompatibility ( HLA sensitisation) poses an immunologically challenging situation and such patients might be considered for paired kidney donation ( Swap Renal Transplantation)
TYPE OF STUDY:
Prospective Cohort Study
Level-2 Evidence
Summarise the conclusion of this article
Anti HLA antibodies can develop due to exposure to HLA antigen resulting from previous blood transfusions, pregnancy and previous transplants. ABOi and positive cross match is a contraindication to transplantation due to high risk of hyper acute rejection and acute AMR. New diagnostic techniques like solid phase assays, desensitization protocols have made it possible to cross HLA and ABO incompatibility barriers. CONCLUSION
ABO incompatible kidney transplantation ( ABOi-KT) has excellent 1 year graft and patient survivals i.e., 97% patient and graft survival 95% at one year.
Donor specific antibodies (DSA) of anti-HLA type is a risk factor for subclinical rejection, acute vascular rejection and chronic rejection which will lead to worst graft survival.
HLA and ABO incompatibility together are considered high risk for graft rejection , rendering Kidney exchange program a more favourable option
the hazardous effect of DSA on graft survival is even more than that cuased by anti- ABO antibodies.
DSA with mean fluorescence intensity (MFI) of more than 5000 by single antigen bead assay (SAB) in patients with ABOi-KT, will result in poorer graft outcome even with desensitization.
Desensitization protocols in ABOi before transplant can reduce anti HLA DSA levels but antibody rebound occurs after transplant causing ABMR and graft loss. What is the type of this study and the level of evidence?
Prospective Cohort study
Level of evidence -II
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO- incompatible renal transplantation.
It is a prospective study on 66 patients on dialysis evaluated before ABOi transplantation for HLA antibody by CDC , Flow cross match and single antigen bead assay.
All received desensitization protocol for ABO I transplantation in the form of (Rituximab 2 weeks before, PEX with IVIg and induction by basiliximab or ATG with steroid and maintained on tacrolimus based therapy).
By comparing non-sensitized group which was 50 patients with MFI ≤1000 on SAB assay to sensitized group (n = 16, MFI≥1000)
Showed that patient survival was 97% and graft survival was 95% at one year and at four years and patient survival was 91.6% and graft survival was 91.5% respectively.
There is increased ABMR and graft loss in sensitized patients with anti-HLA antibodies (DSA).
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
Prospective cohort study.
Level of evidence II.
To evaluate the out come of combined HLA and ABO incompatibility kidney transplantation. So patients were evaluated for antibody mediated rejection (ABMR), donor specific anti HLA sensitization, graft survival with anti HLA DSA positivity in ABO-incompatible kidney transplant recipients.
Population;
Sixty six patients .
Patient selection;
Patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation.
Antibody testing ;
To standardize results, HLA labs need to identify cut off (MFI) values for significance for Luminex based solid phase tests when compared with traditional CDC and flow cross match results .
Gel card method was used to measure anti ABO titers.
IgM ABO antibody titers are done by neutral gel cards on serially diluted patient serum.
IgG ABO antibody titers were done using AHG gel cards. Anti- Blood group titer of 1:8 is the target.
The ABO titration was performed before and after every session of PP/ IVIg .
Desensitization Protocol ;
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which is administered, 10 to 12 days prior to kidney transplant (KT).
2 to 10 sessions of plasmapheresis were given (depending on the anti- ABO titer) performed over 2 to 14 days before surgery until a recipient’s isoagglutinin titer decreased to a level below 1:8.
Postoperative plasmapheresis was given if the anti-A,B isoagglutinin titer increased significantly above a level of 1:8 (within first two weeks of transplant) associated with graft dysfunction with allograft biopsy suggestive of ABMR.
Immunosuppressant protocol;
All the ABO-i KT patients received induction therapy with either Basiliximab (an anti-CD25 monoclonal antibody) (on day 0 and 4) or Rabbit anti- thymocyte globulin (ATG) induction in high-risk patients was given in a total dose of 3–4.5 mg/kg on in three doses given day zero and then alternate days post-transplant.
The patients received triple sequential immunosuppression – mycophenolate mofetil (MMF; dose – 1500–2000 mg/day) and tacrolimus (dose – 0.1 mg/kg daily; adjusted to a 12 h, trough levels of 8–12 ng/ ml) and low dose steroids prednisolone were started 10 days prior to surgery.
The study result ;
Anti HLA DSA positivity with ABO- incompatibility is associated with poor graft survival.
Conclusion;
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation.
What is the type of this study and the level of evidence?
This study assessed 66 patients for DSAs prior to ABOi-KT using CDC, FCXM, SAB, & lysate based solid phase XM. The patients were divided into two groups ; Group A(non-sensitized) & group B(sensitized patients). All patients were de-sensitized for average of 11 days before transplantation. They were assessed for ABMR,DSA, and graft survival.
The study concluded that; Desensitization didn’t help sensitized patients with transplant DSA > 5000. Combination of both HLA-incompatible and ABOi- transplantation were associated with adverse graft outcomes in particular when transplant DSA was > 5000.
Although desensitization decrease Anti A/B titers significantly before transplantation, DSAs can rebound after desensitization and results in ABMR and graft loss.
Therefore,this combination of double incompatibility(HLAi + ABOi)should best be avoided and the pairs can be enroll into paired kidney donation scheme to obtain better transplant outcomes.
This is prospective cohort study and level II evidence
Introduction:
– Our bodies become sensitized in 3 main ways, pregnancy, blood transfusion, and previous transplantation. ABO-incompatible transplant in sensitized recipient is associated with increased risk for ABMR and inferior graft outcomes.
– ABOi transplant is one of the strategies done to overcome the donor pool shortage. It could by done after the development of advanced techniques regarding the detection of preformed antibodies, decreasing their levels, and subsequent management preventing their new formation.
-In this study, 66 kidney recipients were evaluated for HLA sensitization before receiving ABOi graft. HLA sensitization was tested by CDC-XM, FC-XM, single antigen bead using Luminex and finally, lysate-based solid phase crossmatch. Anti ABO abs were detected by gel cards (neutral gel cards for ABO IgM and AHG for IgM).
– Then they were prospectively included, they were divided according to their risk as group A with MFI <1000 and high-risk group with MFI > 1000. The induction regimens were basiliximab or ATG for sensitized patients. All were maintained on triple immunosuppression including tacrolimus, MMF, and steroids. Desensitization protocols were done with target 1/8 and negative CDC XM.
The results:
Five of the 66 patients developed ABMR, accounting for 4% in non-sensitized patients and 18.8 in sensitized patients. Rebound DSA level increase in the sensitized group. More aggressive ABMR in the sensitized group with MFI above 5000 and they lost their graft 1 week after transplantation.
Conclusion:
Despite the excellent one-year survival of ABOi transplantation, those with pre-transplant DSA with MFI above 5000 had poor outcomes even after desensitization. The presence of both barriers’ high sensitization and ABO incompatibility carry a poor prognosis and warrant searching for a more suitable solution i.e. paired exchange donation.
This study is an observational prospective cohort study with level 2 of evidence that has evaluated and compared the kidney transplant outcomes in the ABO incompatible kidney transplant in the presence and absence of donor specific anti-HLA sensitization.
For expanding the donor pool, ABO-incompatible (ABO-I) renal transplantation is considered as an option.
Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of antibody- mediated rejection (AMR), and graft loss. Presence of both ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss. Development of new techniques such as gel card for ABO titer and, solid phase anti-HLA antibody assays to evaluate histocompatibility barriers, has improved our ability to assess and predict the risk of presence of ABOi, and HLA incompatibility. In addition, there has been great improvement in therapeutic options for management ABOi and HLA sensitization that reduce the risk of acute AMR.
An ABO or HLA incompatible organ desensitization protocols provides the basic mechanisms to modulate the immune system consists of Splenectomy and cytotoxic therapies such as rituximab and bortezomib for depleting the size of B and plasma cell clones. Removal of circulating antibodies is accomplished by procedures such as plasmapheresis or double filtration or immunoadsorption. IVIG may also directly inhibit the function of circulating antibodies.
In this study patients with ABOi were evaluate for HLA sensitization by CDC, flow PRA and SAB.
A positive flow crossmatch can pick up low level of DSA, which is missed
by CDC crossmatch. Both CDC and flow crossmatch assays should be done before transplant especially, in sensitized recipients and repeat transplants.
In SAB assay, each bead detects antibody directed against a single HLA antigen. Median fluorescence intensity (MFI) values of SAB assay semi-quantitatively estimate of the intensity of each anti-HLA antibody present. Multiplex bead antibody assay systems for anti-HLA antibodies use a solid phase platform consist of all of the most frequently observed HLA alleles (97 class I and 91 class II alleles).
DSA screening by lysate-based crossmatch assay identifies anti-HLA antibodies for class I and class II and their titer without capability to give the HLA specificities.
IgM ABO antibody titers are done by neutral gel cards and IgG ABO antibody titers are done using AHG gel cards. Anti- Blood group titer of 1:8 is the target. In this study, desensitization protocols were rituximab and plasmapheresis with the aim of decreasing isoagglutinin level below 1/8 before and within 2 weeks after kidney transplantation.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized group, ABMR was seen in 4.0% and in sensitized group ABMR was seen in 18.75% with DSA positivity. Graft loss within one month post-transplant was seen in 2 patients due to ABMR in the sensitized group with pretransplant positive DSA and in none in the non-sensitized group.
ABO incompatible renal transplantation has excellent one year graft and patient survival. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
This study concluded that Anti HLA DSA positivity with ABO-incompatibility is associated with poor graft survival.
Conclusion of the article:
Pre-operative anti-HLA DSA carries high risk for the development of ABMR and have inferior outcome regarding graft survival in ABOi transplantation despite of desensitization therapy. Patients with combined incompatibility(ABOi and HLAi) are better to be advised for swabbing or other alternatives than proceeding to transplant with this risky combined incompatibility even if desensitization therapy is used.
Study type : Observational prospective cohort study.
Level of evidence: type 2.
The study is a prospective observational study with level of evidence being 2 conducted by SGPGI Lucknow India
ABOi and Anti HLA antibodies causing high DSA are both contraindicated for renal transplants due to the higher risk of ABMR….Ideally swap transplants, selection of blood group compatible donor or getting listed in deceased donor renal transplant program are the available options
66 patients who were for ABO incompatible renal transplants were evaluated for donor specific antibodies by SAB Luminex, CDD and Flow cytometry cross matches. Desensitization protocol was started 10 to 12 days before ABOi renal transplant and HLA i renal transplant…Patients were evaluated for ABMR, donor specific HLA desensitization and graft survival with anti HLA DSA positivity. The results were analyzed after the participants were divided into non sensitized and sensitized group…In non sensitized group ABMR was seen in 4 percent while in the sensitized group ABMR was seen in 18.5%..2 patients had graft loss within 2 months after transplant and these patients had pre transplant high DSA SAB MFI >5000. After desensitization the patients were taken up for surgery….This study quoted a patient and graft survival of 91.4% ad 90% after 4 years of ABOi surgery
Based on the above results they have concluded that anti HLA antibody with high MFI>5000 are associated with poor outcomes after ABOi renal transplants.
Association of ABO_I and specific anti DSA with MFI more than 5000 is considered a high risk transplantation even after desensitization and it is better to go for another option
Level of the evidence is II
Anti-HLA antibodies develop after exposure to foreign HLA antigens through blood transfusions, pregnancies and previous transplants
New technique to evaluate the histocompatibility barriers as antiHLA antibodies and ABO antibodies titers (gel card for ABO titer and, solid phase anti-HLA antibody assays) have improved our ability to regulate the risk of rejection in the presence of ABO and histocompatibility barriers.
ABOincompatible renal transplantation has excellent one year graft and patient survival. But patients going for ABO-I transplant who had single antigen bead assay (SAB)– HLA-DSA positivity with mean uorescence intensity (MFI) strength above 5000 did poorly despite desensitization. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss. HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation.
It is propective study level 2
ABO i kidney transplant shows excellent one year patient and graft survival while patients with HLA DSA positive and ABO i are associated with poor graft survival especially with MFI strength above 5000 by SAB.
Preoperative Desensitization in ABO i transplant can reduce theses antibodies but they rebound after transplant and can cause ABMR
. Desensitization preoperatively, in ABO-I transplants can reduce anti-HLA antibodies also to acceptable levels, but these antibodies can rebound post-operatively and cause ABMR with graft loss.
1- Summarise the conclusion of this article.
Anti-HLA ab appear if patient expose to graft, pregnancy, blood transfusion.
While anti ABO Ab, is part of innate immunity it is present from fetal development period.
Patient with ABOi transplant who has Ab against HLA with high titer are at high risk of ABMR and graft loss.
ABOi transplantation was used to increase the donor pool.
Presence of these immunological incompatibilities make patient at high risk of hyper acute rejection , acute rejection, and graft loss.
Result
n-66 group A n= 50 (non-sensitize) group B n=16 (sensitized)
Graft survival at 1 month 100% 87.5%
Graft loss at 1 month 0% 12.5%
ABMR 4% 18.7%
No ABMR 96% 81.2%
Conclusion
Graft outcome is better when there is no any immunological incompatibility . With the presence of any immunological barrier the outcome worsen.
Degree of HLA incompatibility which is assessed by the presence and the level of anti HLA Ab.
ABOi also has its own risk carry bad prognostic outcome.
But patient who had high MFI Anti HLA Ab above 5000 (by luminex SAB) and who underwent ABOi kidney transplantation usually has poor outcome.
This double incompatible kidney transplantation associated with high risk of ABMR and poor graft survival.
Paired kidney donation is a best choice in these patient , if it is available . in most country including my country this option is not available , then desensitization will be next option.
Although desensitization of these patient to reduce Anti HLA DSA and isoagglutinin(anti ABO Ab)and to make cross match negative is helpful to transplant these patient but these Ab may rebound and predispose to rejection.
======
2- What is the type of this study and the level of evidence?.
This study is a prospective study with level of evidence of II.
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO-incompatible renal transplantation
Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of antibody- mediated rejection (AMR), and graft loss. Presence of both ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss.
. Patient with anti HLA DSA positivity and ABO incompatibility is associated with poor graft survival especially if MFI strength was more than 5000 .Preoperative desensitization in ABO-I transplants can reduce anti-HLA antibodies also to acceptable levels, but these antibodies can rebound and cause ABMR with graft loss.
DSA at baseline has a more significant impact on graft survival than isoagglutinin in case of combination of ABOi and HLAi transplantation which is considered high-risk to be managed carefully, and patient should preferably go for swap transplantation.
Prospective study, level 2
This is a prospective Cohort study of level 2 evidence
66 dialysis patients were checked for HLA antibodies before ABO incompatible transplantation using the CDC , flow CCx, and single antigen bead assays , all were -ve .
Antibody titers for IgM ABO antibodies are determined using neutral gel cards on serially diluted patient serum while titers of IgG anti-ABO antibodies were determined using AHG gel cards. The goal is to have an anti-blood group titer of 1:8.
After each session of PTx + IVIg, the ABO titration was done before and after each session.
Protocol for immunosuppressive drugs;
The induction therapy for all ABO-i KT patients consisted of either Simulect (on days 0 and 4) or ATG induction in high-risk patients was given in a total dose of 3–4.5 mg/kg on three doses given startin on day zero .
Triple IS : FK , MMF , steroids which started 10 days before surgery and continues .
Anti-HLA DSA positive in conjunction with ABO incompatibility was associated with poor graft survival.
This study is an observational prospective cohort study with level 2 of evidence that has evaluated and compared the kidney transplant outcomes in the ABO incompatible kidney transplant in the presence and absence of donor specific anti-HLA sensitization.
For expanding the donor pool, ABO-incompatible (ABO-I) renal transplantation is considered as an option.
Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of antibody- mediated rejection (AMR), and graft loss. Presence of both ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss. Development of new techniques such as gel card for ABO titer and, solid phase anti-HLA antibody assays to evaluate histocompatibility barriers, has improved our ability to assess and predict the risk of presence of ABOi, and HLA incompatibility. In addition, there has been great improvement in therapeutic options for management ABOi and HLA sensitization that reduce the risk of acute AMR.
An ABO or HLA incompatible organ desensitization protocols provides the basic mechanisms to modulate the immune system consists of Splenectomy and cytotoxic therapies such as rituximab and bortezomib for depleting the size of B and plasma cell clones. Removal of circulating antibodies is accomplished by procedures such as plasmapheresis or double filtration or immunoadsorption. IVIG may also directly inhibit the function of circulating antibodies.
In this study patients with ABOi were evaluate for HLA sensitization by CDC, flow PRA and SAB.
A positive flow crossmatch can pick up low level of DSA, which is missed
by CDC crossmatch. Both CDC and flow crossmatch assays should be done before transplant especially, in sensitized recipients and repeat transplants.
In SAB assay, each bead detects antibody directed against a single HLA antigen. Median fluorescence intensity (MFI) values of SAB assay semi-quantitatively estimate of the intensity of each anti-HLA antibody present. Multiplex bead antibody assay systems for anti-HLA antibodies use a solid phase platform consist of all of the most frequently observed HLA alleles (97 class I and 91 class II alleles).
DSA screening by lysate-based crossmatch assay identifies anti-HLA antibodies for class I and class II and their titer without capability to give the HLA specificities.
IgM ABO antibody titers are done by neutral gel cards and IgG ABO antibody titers are done using AHG gel cards. Anti- Blood group titer of 1:8 is the target. In this study, desensitization protocols were rituximab and plasmapheresis with the aim of decreasing isoagglutinin level below 1/8 before and within 2 weeks after kidney transplantation.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized group, ABMR was seen in 4.0% and in sensitized group ABMR was seen in 18.75% with DSA positivity. Graft loss within one month post-transplant was seen in 2 patients due to ABMR in the sensitized group with pretransplant positive DSA and in none in the non-sensitized group.
ABO incompatible renal transplantation has excellent one year graft and patient survival. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
This study concluded that Anti HLA DSA positivity with ABO-incompatibility is associated with poor graft survival.
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO- incompatible Renal Transplantation.
This is a prospective cohort single centre study in India with level II evidence. The objective of this research is to assess for antibody mediated rejection (ABMR), donor specific anti HLA sensitisation, graft survival with anti HLA DSA positivity in ABO-incompatible kidney transplant recipients upon 4 years follow up. A total of 66 end stage renal failure patients on dialysis were recruited. The mean age (34.56±11.13). 98.4% of the subjects received tacrolimus and 1.6% on cyclosporine as immunosuppressant. At the time of transplant 62.5% of subjects received Basiliximab and the remaining 37.5% received ATG as induction. CDC, flow crossmatch were negative for all subjects at the time of transplant. The donor-specific antibody with mean fluorescence intensity (MFI) of more than 1000 were present in two subjects; 3.0%, whereas 64 subjects had MFI less than 500; 97.0% on SAB assay. The outcomes are better in non-sensitised group with 100% graft survival and 0% graft loss at 1 month. ABMR was seen in 4.0% of subject. However, the sensitised group reported statistic significant graft loss due to ABMR in 3 subjects (8.75%) of which 2 subjects happened within one week post-transplant. Both these patients had SAB DSA positivity, with total MFI strength above 5000 before desensitisation. After desensitisation the MFI came down to less than 1000 at the time of transplant, but showed significant rebound after ABOi transplant resulting in severe ABMR and graft loss. Patient survival was 97% and graft survival was 95% at one year of follow up. At four years post transplantation patient survival was 91.6% and graft survival was 91.5%. In conclusion, ABO incompatible renal transplantation has excellent one year graft and patient survival except those with single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000. HLA and ABO incompatibility in combination has poor outcome in term of patient and graft survival despite desensitisation. Swap transplant provide alternative to overcome the immunological barrier.
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO-incompatible renal transplantation
ABO-incompatible kidney transplantation has excellent one-year graft and patient survival. Patient with anti HLA DSA positivity and ABO incompatibility in combination is associated with poor graft survival especially if MFI strength was more than 5000 by SAB. Desensitization preoperatively, in ABO-I transplants can reduce anti-HLA antibodies also to acceptable levels, but these antibodies can rebound post-operatively and cause ABMR with graft loss.
DSA at baseline has a more significant impact on graft survival (ABMR) than isoagglutinin in the case of combined ABOi and HLAi transplantation which is a high-risk situation that needs to be adjusted carefully, and the patient should preferably go for swap transplantation.
its prospective study, level 2
ABO incompatible transplant recipients with anti-HLA antibodies have higher risk of AMR and graft loss.
The study conducted to assess the effect of donor specific anti HLA sensitization on ABOi KTR
66 patients underwent ABOi KT, out of which 16 patients were sensitized. AMR was seen in 5 out of 66 patients (7.5%). In the sensitized group, AMR was seen in 18.75% (3 out of 16), while it was seen in 4% (2 out of 50) of non-sensitized patients.
Graft loss was seen in 2 out of the 3 sensitized patients with AMR and both had MFI >5000 before desensitization. The overall patient and graft survival at 1 and 4 years was 97% and 95% and 91.6% and 91.5%.
The conclusions derived include:
What is the type of this study and the level of evidence?
This is a prospective cohort study.
Level of evidence: Level II
ABO incompatible increase the numbers of donor in renal transplantation and has very good outcome . But when it associated with DSA (MFI) more than 5000 despite desensitization this combination lead to very poor graft survival due to acute AMR . Desensitization in ABO-I transplants can reduce anti HLA antibodies at time of transplantation , after transplant antibodies can rebound and cause ABMR with graft loss. Also there are great risk of infection in such condition pair exchange is advisable .
What is the type of this study ?
Prospective cohort study .
the level of evidence?
Level 2
Donor specific anti HLA sensitization is associated with inferior short-term outcomes in ABO-incompatible renal transplantation
Sonia Mehrotra, Raj Kumar Sharma⁎, Kavita Vishwakarma, Narayan Prasad, Amit Gupta, Dharmendra S. Bhadauria, Anupama Kaul
ABOi kidney transplantation was a solution for 30% of cases that had donors but unfortunately ABO incompatible with the recipient
This was before absolute contraindication for kidney transplantation but it was overcome by desensitization protocols.
Desensitization protocol for ABOi is almost the same protocol of desensitization of anti HLA antibodies, so theoretically it may be cost beneficial to do a transplant against ABOi in HLA DSA patients to remove both kinds of antibodies
In this study, sixty-six patients were evaluated for donor-specific anti-HLA sensitization before they received ABO-incompatible kidney transplantation. Then the patients were divided to 2 groups group A 50 patients (non-sensitized) and group B 16 patients(sensitized)
Antibodies screening for each recipient was evaluated by complement-dependent cytotoxicity (CDC) crossmatch, flow cytometric crossmatch, single antigen bead assay (SAB) and lysate-based solid-phase crossmatch.
Standard desensitization protocol was started 10 to 12 days prior to kidney transplant for ABO-incompatible and anti-HLA incompatible transplants. A regimen of desensitization was modified according to anti the A/B IgG titer targeting level 1:8.
Patients were evaluated for antibody-mediated rejection (ABMR), donor-specific anti-HLA sensitization, and graft survival with anti-HLA DSA positivity in ABO-incompatible kidney transplant recipients.
Antibody-mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized group-A, ABMR was seen in 4.0%, and in the sensitized group (group B) ABMR was seen in 18.75% with DSA positivity.
Graft loss within one-month post-transplant was seen in 2 patients due to ABMR in group -B and non in group-A (p-value = 0.05). Both two were transplanted with CDC and flow CM negative after desensitization and had SAB DSA MFI strength came down to ≤1000 which means memory carries a very high risk of rejection even with acceptable parameters pretransplant.
In this study patient survival was 97% and graft survival was 95% at one year, at four years Patient survival was 91.6% and graft survival was 91.5% follow up period. Anti HLA DSA positivity with ABO- incompatibility is associated with poor graft survival even after successful desensitization.
level of evidence
its prospective cohort study but with a poor design especially the study group is numerically not matched with a control group
level of evidence 2
Summarize the conclusion of this article:
ABO incompatible renal transplantation is a risky procedure but it is worthy in general and of good patient and graft survival about 97 % compared to deceased donor Tx.
Risk of acute ABMR increases with the presence of HLA incompatibility together, especially with high MFI exceeding 5000 even after desensitization due to rebound phenomenon after Tx.
Besides of risk of infections due to increased immunosuppression status of these patients.
The type of this study and the level of evidence:
Prospective Cohort Study
Level of evidence 2
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
This is a primary study prospective cohort – level 02 of evidence.
Thanks, Carlos
Nice to see your contribution. I advise you to read the others’ contributions as well
# Summarise the conclusion of this article
Summary:
# Exposure to foreign HLA antigens from blood transfusions, pregnancies and previous transplants can result in development of Anti HLA antibodies.
# Patients have both ABO incompatible and anti HLA DSA are at high risk of AMR and graft loss.
# ABO incompatible and positive cross match are contraindication to transplantation because the risk of hyper acute or acute AMR.
# New methods to evaluate anti HLA and ABO antibodies titers (gel card for ABO titer and, solid phase anti HLA antibody assays) and to remove or decrease it’s production by modulating the immuneresponse prior to transplantation to minimize the risk of rejection episodes.
Result:
** In this study 66 patients were evaluated for the DSA before they received ABO- I kidney transplantation and all of them evaluated by CDCXM, FCMXM, SAB and lysate based solid phase crossmatch.
** The desensitization protocol was started10 to 12 days prior kidney transplant for all patients.
** Patients were evaluated for ABMR, DSA and graft survival.
* ABMR was seen in 5 patients(7.5%).
* In non sensitized (group A) ABMR was seen in 4.0%.
*In sensitized (group B) ABMR was seen in 18.75% with positive DSA.
* Graft loss within one month posttransplant was seen in 2 patients due to ABMR in the sensitized group -B with pretransplant positive DSA and in none in the non-sensitized group-A (p value = 0.05).
*Both these 2 patients had FCXCM, SAB DSA and Lysate CM positivity, with total MFI strength by SAB more than 5000
*These 2 patients with CDC and FCXCM became negative after desensitization and MFI decrease to1000.
* At one year patient survival was 97% and graft survival was 95%.
*At four years patient survival was 91.6% and graft survival was 91.5%.
*Positive DSA with ABO- I is associated with poor graft survival.
# Conclusion
*ABO incompatible renal transplantation has excellent one year graft and patient outcomes.
* ABO-I with positive HLA-DSA (MFI) more than 5000 by SAB assay has poor outcomes despite desensitization.
* Preoperative desensitization in ABO-I can reduce anti HLA DSA, but it can rebound after transplant and cause ABMR with graft loss.
* Anti HLA antibodies and ABO- I in combination is at high immunological risk situation, so better to go for paired exchange kidney donation.
# What is the type of this study and the level of evidence?
Prospective Cohort Study
Level of evidence 2
Thanks Elaf
◇Donor specific anti HLA sensitization is associated with inferior short term
outcome in ABO- incompatible renal transplantation
¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤
☆Introduction:
________________
▪︎An ABO or HLA incompatible organ desensitization protocols provides the basic mechanisms to modulate the immune system as splenectomy and cytotoxic therapies such as rituximab and bortezomib decrease the size of B and plasma cell clones.
▪︎Physical removal of circulating antibodies is accomplished by plasmapheresis, double filtration or immunoadsorption.
▪︎IVIG may also directly inhibit the function of circulating antibodies.
☆ Materials and methods:
_____________________________
▪︎Sixty six patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation.
▪︎ Each recipient was evaluated by complement dependent cytotoxicity (CDC)
crossmatch, flow cytometric crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch .
▪︎The desensitization protocol was started10 to 12 days prior kidney transplant for ABO incompatible and anti HLA incompatible transplants.
▪︎ Patients were evaluated for antibody mediated rejection (ABMR), donor specific anti HLA sensitization, graft survival with anti HLA DSA positivity in ABO-incompatible
kidney transplant recipients.
☆ Results:
___________________________
▪︎Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients.
▪︎In non-sensitized group-A, ABMR was seen in 4.0% and in sensitized group (group-B) ABMR was seen in 18.75% with DSA positivity.
▪︎ Graft loss within one month post-transplant was seen in 2 patients due to ABMR in the sensitized group -B with pretransplant positive DSA and in none in the non-sensitized group-A (p value = 0.05). Both these two patients sensitized group -B had flow CM, SAB DSA and Lysate CM positivity, with total MFI strength by SAB was above 5000, these two patients with CDC and flow CM negative after desensitization and had SAB DSA MFI strength came down to ≤1000.
▪︎In this study patient survival was 97% and graft survival was 95% at one year, at four
years patient survival was 91.6% and graft survival was 91.5% follow up period.
▪︎ Anti HLA DSA positivity with ABO- incompatibility is associated with poor graft survival.
☆Conclusion:
_______________
▪︎One year graft and patient survival in ABO incompatible renal transplantation is excellent . But patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean
fluorescence intensity (MFI) strength above 5000 did poorly despite desensitization.
▪︎Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB
assay.
▪︎ Desensitization in ABO-I transplants can reduce anti HLA Abs also to acceptable levels but the anti-HLA Abs can rebound after transplant and cause ABMR with graft loss.
▪︎It is preferable to go for swap transplantation in combined HLA and ABO incompatibility.
● Type of the study: prospective cohort
●Level of evidence: II
Thanks Tahni
66 patients with end stage of kidney failure (92.2% male, 7.8% female) on dialysis their age mean (34.56 ± 11.13), were evaluated prospectively before ABO incompatible kidney transplantation.
Patients were evaluated for donor specific anti HLA sensitization by complement dependent cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch. Gel card method was used to measure anti ABO titers. AntiBlood group titer of 1:8 is the target. The ABO titration was performed before and after every session of PP/ IVIg.
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which is administered, 10 to 12 days prior to kidney transplant (KT). 2 to 10 sessions of plasmapheresis (anti- ABO titer) performed over 2 to 14 days before surgery until a recipient’s isoagglutinin titer decreased to a level below 1:8. Postoperative plasmapheresis was given if the anti-A,B isoagglutinin titer increased significantly above a level of 1:8 (within first two weeks of transplant) associated with graft dysfunction with allograft biopsy suggestive of ABMR.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized, group-A (n = 50, MFI ≤1000 on SAB assay) ABMR was seen in 4.0% of patients. In sensitized, group-B (n = 16, MFI≥1000), ABMR was seen in 18.75% of patients, with rebound of DSA positivity. Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in the sensitized group -B (p value = 0.05). Both these patients had SAB DSA positivity, with total MFI strength above 5000 before desensitization. After desensitization the MFI came down to ≤ 1000 at the time of transplant, but showed significant rebound after ABOi transplant resulting in severe ABMR and graft loss. Suggesting that patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000 did poorly despite desensitization. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
Patient survival was 97% and graft survival was 95% at one year and at four years Patient survival was 91.6% and graft survival was 91.5%.
HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation.
Prospective study, level 1 of evidence
Prospective study, level 2 of evidence
Thanks
This is a prospective cohort study. so it’s level of evidence is II.
conclusion:
Althoug ABOi transplantation have excellent 1 year graft survival the higher MFI (more than 5000) the worse the prognosis. Ther rebound of DSAs is expected . The worst prosnosisi is in case of combined HLA and ABO incompatibility. In such case, paired exchange is worth.
This is very short Mahmud
Outcome of HLA sensitized patient comparing non-sensitized ABO incompatible kidney transplantation were evaluated in 66 patients. Five patients had ABMR, 4% in non-sensitized and 18.75% in sensitized patient and two graft loss was seen only in sensitized group. They concluded that HLA incompatible TX in context of ABOi-KT, is associated with poor graft survival. This is true especially if MFI was more than 5000. Because even after desensitization, DSA could rebound after TX and resulted in ABMR or even graft loss. So in this situation, choosing another options such as KPD is reasonable. This is a prospective cohort study with level of evidence 2.
Thanks Nasrin
Introduction
Anti-HLA antibodies develop after exposure to foreign HLA antigens
through blood transfusions, pregnancies and previous transplants.
Patients of ABO incompatible transplants who have antibody against
their donor HLA antigens with high strength are at high risk of antibody-
mediated rejection (AMR), and graft loss.
Materials and methods
Patient selection
Patients were evaluated for donor specifc anti HLA sensitization
before they received ABO incompatible kidney transplantation. Each
recipient was evaluated for anti-HLA sensitization by complement dependent
cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen
bead assay (SAB) and lysate based solid phase crossmatch.
Flow cross match serves as a sensitive cross match test for the detection
of DSA
The solid phase assays like (single antigen bead assay) SAB, detect
anti-HLA antibodies against the donor. Single antigen bead (SAB) assays
have increased sensitivity and specificity of detecting anti-HLA
antibodies results. A limitation of solid phase assays is that the beads could be coated with HLA molecule which could get altered during recombinant processing
Gel card method was used to measure anti ABO titers. Anti- Blood group titer of 1:8 is the target.
Desensittzation protocol with Rituximab , aphresis therapy preoperatively until isoagglutinin titre is less than 1:8 , postop aphresis is applied if the anti-A,B isoagglutinin
titer increased significantly above a level of 1:8 (within first two weeks
of transplant) associated with graft dysfunction with allograft biopsy
suggestive of ABMR.
On 66 studied patients , Antibody mediated rejection (ABMR) was seen in five (7.5%) patients. In non-sensitized, group-A (n = 50, MFI <1000 on SABassay) ABMR was seen in 4.0% of patients. In sensitized, group-B (n = 16, MFI>1000), ABMR was seen in 18.75% of patients, with rebound of DSA positivity. Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in
the sensitized group -B (p value = 0.05). Both these patients had SAB
DSA positivity, with total MFI strength above 5000 before desensitization.
After desensitization the MFI came down to ! 1000 at the time
of transplant, but showed signi!cant rebound after ABOi transplant
resulting in severe ABMR and graft loss
Discussion
Results shows that patients who were going for ABO-I transplant
who had anti-HLA antibodies before desensitization had increased
ABMR. Desensitization protocols effectively result in successful ABO-I
renal transplantation, but there is increased ABMR and graft loss in
sensitized patients with anti-HLA antibodies (DSA).
Although various desensitization strategies are attempted to overcome immunologic barriers to transplantation , however , there are still problems of de novo Abs and the rebound of Abs ( especially in those with high Ab level before desensitization )
Chung BH et al suggested that HLAi is more determining for the incidence of acute ABMR than ABOi . Loupy et al. and Amico et al. have reported that preformed DSA
antibodies correlate with a high incidence of subclinical AMR
both late rejections and resistance to treatment are strongly
associated with class II DSA, especially HLA-DQ, antibody
CONCLUSION
ABO incompatible renal transplantation has excellent one year graft
and patient survival. But patients going for ABO-I transplant who had
single antigen bead assay (SAB) – HLA-DSA positivity with MFI strength above 5000 did poorly despite desensitization. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies
can rebound after transplant and cause ABMR with graft loss
Type : Prospective cohort study , level 2
Well done Nawaf
Summary
This report is concerned with anti HLA sensitization specifically for the donor and how this process may not have the expected outcomes but instead have poor short term outcome for ABOi kidney transplant.
In ABOi transplant, presence of HLA antibodies before desensitization is linked with ABMR. Desensitization results in successful ABOi transplants. Sensitized patients have increased risk of ABMR and graft loss.
De novo antibodies can lead to ABMR. Patients undergoing combined ABOi and HLAi kidney transplants have similar risk of ABMR as patients undergoing HLAi kidney transplant.
AMR impacts long term outcome of kidney transplant. DSA MFI does not correlate the chronicity or severity if AMR. Both late rejection and resistance to treatment are strongly linked with class II DSA, especially HLA DQ antibody.
ABOi renal transplant has been seen to have good one year outcome in terms of graft and patient survival. But patients undergoing ABOi transplant with HLA DSA positive and MFI above 5000 had poor outcome post transplant despite desensitization.
Preoperative desensitization in ABOi kidney transplant can reduce anti HLA antibodies to acceptable levels but rebound post transplant is possible, and this can cause ABMR and graft loss. In the case of combined HLAi and ABOi transplant, it is dangerous in terms of immunology and it is better for the patient to go for swap transplantation.
Type of study
Prospective cohort study
Level of evidence II
Thanks
Prospective cohort observational study with level II .
This study shows that ABO-I kidney transplant patients with anti HLA- antibodies have more chance to develop ABMR although ABO-I transplant has excellent one year patient and graft survival,patients with MFI >5000and ABO-I have poor outcome even when desensitization protocols have been done.
Desensitization protocol can affect on anti HLA-Antibodies causing it to reduce to acceptable level but there will be rebound antibodies leading to ABMR and graft loss.
So the main message of this study is ABO-I with HLA (especially high titer)can put the patient in high immunological risk.
Thanks
ABO incompatible kidney transplantation increase the donor pool with good patient and graft survival.
Presence of anti-HLA DSA especially with MFI> 5000 negatively affect the graft survival despite desensitization.
Kidney transplantation in presence of ABO incompatibility and DSA positivity is associated with higher immunological risk
Preoperative desensitization decreases DSA to acceptable levels before transplantation but with risk of antibody rebound post transplant which may lead to AMR and graft loss.
Kidney exchange programs are better alternative for patients with ABO incompatibility and DSA positivity due to the associated high immunological risk
Prospective study
level of evidence: 2
Anti-HLA DSA and ABO incompatibility and positive has been considered a contraindication to transplantation. Sensitized patients due to anti-HLA DSA and ABO incompatibility are at higher risk of graft loss. The presence of blood group isoagglutunins is associated with significant risk of hyper acute or acute AMR.However, the development of desensitization protocols in ABOi and patients with preformed DSA has increased the donor pool.
66 patients with ESRD were included in this prospective study. The aim is to evaluate patient and graft survival in ABOi kidey transplantation in the presence of preformed anti-HLA DSA.
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab, plasmapheresis followed by IVIg (dose – 100 mg/kg per PP session) , until a recipient’s isoagglutinin titer decreased to a level below 1:8.
Induction therapy was either Basiliximab or r-ATG followed by maintenance therapy that included MMF, tacrolimus and steroids.
CDC and flowcytometry crossmatch were negative at time of surgery. DSA MFI were < 1000 after desensitization protocols , except in 2 patients.
Results
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients.
In non-sensitized, group-A ABMR was seen in 4.0% of patients.
In sensitized, group-B, ABMR was seen in 18.75% of patients.
Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in the sensitized group –B.
In conclsion, patients who were going for ABO-I transplant who had anti-HLA antibodies before desensitization had increased ABMR. Patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000 had poor graft survival despite desensitization.
What is the level of evidence?
In ABO-incompatible kidney transplantation, donor-specific anti-HLA sensitization is linked with a worse short-term prognosis than incompatible transplantation.
In this prospective research, 66 dialysis patients were screened for HLA antibodies before to ABOi transplantation using the CDC, flow cross-match, and single antigen bead assays, all of which were negative.
Testing for antibodies;
Luminex-based solid-phase tests, as compared with conventional CDC and flow crossmatch findings, require HLA labs to establish cut off (MFI) values for significance in order to standardize results across laboratories.
The anti-ABO titers were determined using the gel card technique.
Antibody titers for IgM ABO antibodies are determined using neutral gel cards on serially diluted patient serum.
Titers of IgG anti-ABO antibodies were determined using AHG gel cards. The goal is to have an anti-blood group titer of 1:8.
After each session of PP/IVIg, the ABO titration was done before and after each session.
Protocol for immunosuppressive drugs;
The induction therapy for all ABO-i KT patients consisted of either Basiliximab (an anti-CD25 monoclonal antibody) (on days 0 and 4) or Rabbit anti-thymocyte globulin (ATG) induction in high-risk patients was given in a total dose of 3–4.5 mg/kg on three doses given on days zero and then alternate days post-transplant.
The patients were given triple sequential immunosuppression, including mycophenolate mofetil (MMF; dose – 1500–2000 mg/day) and tacrolimus (dose – 0.1 mg/kg daily; adjusted to a 12 h, trough levels of 8–12 ng/ml), as well as low-dose steroids, which were started 10 days before surgery and continued for the duration of the study.
Anti-HLA DSA positive in conjunction with ABO incompatibility is linked with poor graft survival, particularly during the immunological evolution phase if the MFI strength measured by the SAB test was more than 5000, according to the study.
–It is a prospective cohort study.
-Level II
Excellent
This is a prospective cohort study non-experimental observational study
Level 2
66 patients with end stage of kidney failure were evaluated prospectively before renal transplantation.
Patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation.
The patients demographics were :
Age
Patient Sex:Male
Patient Sex:Female
Weight
Height
duration of dialysis
HLA Mismatch
Immunosuppression
Tacrolimus
Cyclosporin
Induction
ATG
Basiliximab
CDC crossmatch
Flow crossmatch
donor-speci!c antibody (DSA) 1000 donor-speci!c antibody (DSA) <1000 age of donor
Donor Sex:Male
Donor Sex:Female
GFR donor
Each recipient was evaluated for anti-HLA sensitization by complement dependent cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch.
Gel card method was used to measure anti ABO titers.
The patients divided into 2 groups
group A(non-sensitized)
group B(sensitized)
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which is administered, 10 to 12 days prior to kidney transplant.
2 to 10 sessions of plasmapheresis were given performed over 2 to 14 days before surgery until a recipient's isoagglutinin titer decreased to a level below 1:8.
Postoperative plasmapheresis was given if the anti-A,B isoagglutinin titer increased signi!cantly above a level of 1:8 (within !rst two weeks of transplant) associated with graft dysfunction with allograft biopsy suggestive of ABMR.
induction therapy include basiliximab and ATG
The patients received triple sequential immunosuppression – mycophenolate mofetil (MMF; dose – 1500–2000 mg/day) and tacrolimus (dose – 0.1 mg/kg daily; adjusted to a 12 h, trough levels of 8–12 ng/ ml) and low dose steroids prednisolone were started 10 days prior to surgery.
The patients and graft survival outcome were studied at one and four year.
Results:
CDC,flow crossmatch were negative for all pa- tients at the time of transplant but donor-speci!c antibody mean fluorescence intensity (MFI) 1000 were present in two patients (3.0%).In rest 64 patients MFI was <500 (97.0%) on SAB assay.
Antibody mediated rejection (ABMR) was seen in five (7.5%) out of 66 patients. In non-sensitized, group-A (n = 50, MFI <=1000 on SAB
assay) ABMR was seen in 4.0% of patients. In sensitized, group-B (n = 16, MFI1000), ABMR was seen in 18.75% of patients, with rebound of DSA positivity.
Graft loss within one week post-transplant was seen in 2 patients due to ABMR with rebound of DSA only in the sensitized group -B .Both these patients had SAB DSA positivity, with total MFI strength above 5000 before desensitization.
Patient survival was 97% and graft survival was 95% at one year and at four years Patient survival was 91.6% and graft survival was 91.5%.
This study shows that patients who were going for ABO-I transplant who had anti-HLA antibodies before desensitization had increased ABMR. Desensitization protocols e#ectively result in successful ABO-I renal transplantation, but there is increased ABMR and graft loss in sensitized patients with anti-HLA antibodies (DSA).
In Conclusion:
ABO incompatible renal transplantation has excellent one year graft and patient survival. But patients going for ABO-I transplant who had single antigen bead assay (SAB) – HLA-DSA positivity with mean fluorescence intensity (MFI) strength above 5000 did poorly despite desensitization. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss. HLA and ABO incompatibility in combination is a high risk situation from im- munological point of view. In such a situation patient should preferably go for swap transplantation.
Well done
Anti-HLA antibodies develop after exposure to foreign HLA antigens through
blood transfusions
pregnancies and
previous transplants.
As reported previously Patients of ABO incompatible transplants who have antibody against their donor HLA antigens with high strength are at high risk of anti- body-mediated rejection (AMR), and graft loss . To address this issue this study was conducted to confirm that Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO- incompatible renal transplantation.
Patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation. Each recipient was evaluated for anti-HLA sensitization by complement dependent cytotoxicity (CDC) crossmatch, flow crossmatch, single antigen bead assay (SAB) and lysate based solid phase crossmatch.
The desensitization protocol for ABO incompatible transplant included infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which was administered, 10 to 12 days prior to kidney transplant (KT). 2 to 10 sessions of plasmapheresis were given (depending on the
anti- ABO titer) performed over 2 to 14 days before surgery until a recipient’s isoagglutinin titer decreased to a level below 1:8.
Induction was either with basiliximab or ATG.
66 patients underwent ABO incompatible kidney transplant, out of which 16 patients were sensitized. AMR was seen in 5 out of 66 patients (7.5%). In the sensitized group, AMR was seen in 18.75% (3 out of 16), while it was seen in 4% (2 out of 50) of non-sensitized patients.
Graft loss was seen in 2 out of the 3 sensitized patients with AMR and both had MFI >5000 before desensitization. The overall patient and graft survival at 1 and 4 years was 97% and 95% and 91.6% and 91.5%.
Conclusion
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
. HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation
Well done
In summary
since succeed to overcome the barriers of ABO incompatible and positive cross match which has been considered as contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss via therapeutic options of desensitization protocols.
1. Removal of circulating antibodies via plasmapheresis, or immunoadsorption and decrease production of anti-AB and anti-HLA antibodies.
2. The supplementary immunosuppressive medications as well as IVIG via Fc receptor signaling pathways impair the ability of cells to make antibodies.
Aiming to reduce the risk of rejection through immune modulation pre transplant
Cohort study was conducted; sixty-six patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation. (CDC, flow cytometry cross match, (SAB) and lysate based solid phase cross match). The desensitization protocol was started10 to 12 days’ prior kidney transplant for ABO incompatible and anti HLA incompatible transplants at our center. Patients were evaluated for antibody mediated rejection (ABMR), donor specific anti HLA sensitization, graft survival with anti HLA DSA positivity in ABO-incompatible kidney transplant recipients.
Conclusion
1. Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
2. Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
3. HLA and ABO incompatibility in combination is a high risk situation from immunological point of view.
4. In such a situation patient should preferably go for swap transplantation.
What is the type of this study and the level of evidence?
Prospective Cohort study.
Level of evidence -II
Excellent
Prospective cohort study
Level of evidence: II
This is a prospective study involved 66 patients who undergone ABOi transplantation after desensitization protocol aiming at antibody titer of less than 1/8, Meanwhile pretransplant HLA assessment revealed 16 patients sensitized with SAB of more than 1000 MFI. AMR was reported in 3/16 patients in sensitized group and in 2/50 patients in non sensitized group, Rebound of DSAs was noticed and correlated with incidence of AMR. There was no rebound of AB antibodies
This study concluded that there is an increased incidence of AMR for patients who undergone ABOi transplant who are concurrently HLA incompatible.
I believe the result is not consistent and non related to anti ABOi transplantation, as the incidence of AMR is directly and conclusively related to rebound of DSAs or emergence of De novo HLA antibodies and there was no correlation to Anti B, A antibodies titer which was entirely maintained within the pre transplant titer with no rebound, refuting any link to the AMR. Furthermore the size of sample was small.
The study is prospective with level of evidence of 1
I mean level of evidence 2
Thanks Wael
· Summarise the conclusion of this article:
Anti HLA antibodies can develop due to exposure to HLA antigens resulting from previous blood transfusions, pregnancy, and previous transplants.
ABOi and positive crossmatch is a contraindication to transplantation due to the high risk of hyperacute rejection and acute AMR.
Recipients with ESRD who are planned for ABOi-KT were evaluated for pre-formed Anti HLA antibodies.
Donor-specific anti-HLA sensitization is associated with inferior short-term outcome in ABO-incompatible renal transplantation.
· ABOi-KT has increased the potential donor pool.
· Desensitization protocol modulates the immune system aiming to reduce antibodies titers (ABO&HLA) and to reduce the risk of ABMR posttransplant.
ABO-incompatible renal transplantation has excellent one year graft and patient survival.
· Patients going for ABO-I transplant who had DSA with MFI > 5000 did poorly despite desensitization and is associated with poor graft survival
· Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to acceptable levels but the anti-HLA antibodies can rebound after transplant and cause ABMR with graft loss.
· HLA and ABO incompatibility in combination is an immunologically high risk. And preferred to go for paired exchange transplant.
What is the type of this study and the level of evidence?
Prospective Cohort study.
Level of evidence -II
this is an obervational (prospective)studty with level of evidence 2
Short and sweet Mohamed
-ABO incompatible and positive crossmatch barrier has been considered a contraindication to transplantation and has a signifcant risk of hyperacute or acute AMR and graft loss due to the presence of blood group antibodies or HLA antibodies in the recipient.
– Patients who have positive PRA or patients with persistent weakly positive cross matches may require therapy before transplant, lowing antibody titers (ABO and HLA) so that crossmatch becomes negative per transplant this reduces the risk of acute ABMR post-transplant especially in anti-HLA sensitized about transplant.
– 66 patients with end-stage kidney failure enrolled in study.
-Patients who were going for ABO-I transplant who had anti-HLA antibodies before desensitization had increased ABMR.
-Desensitization protocols effectively result in successful ABO-I renal transplantation, but there is increased ABMR and graft loss in
sensitized patients with anti-HLA antibodies (DSA).
– There could be a rebound of ant HLA DSA or anti-ABO antibody in high anti-ABO antibody producers which are difficult to desensitize.
-One study showed that KT in patients with combined ABOi and HLAi had a similar incidence of acute AMR to that in exclusively HLAi patients, and was inferior to that in ABOi patients or high baseline titer of anti-A/B antibody was no longer a significant predictor for acute AMR when the HLAi group was included, but a strong HLA-DSA at baseline was still a significant risk factor for acute AMR even when the ABOi group was included.
-Pre-transplant DSA is a risk factor for rejection, and preformed antibodies correlate with a high incidence of subclinical AMR and that pre-Tx DSA was associated with acute vascular and chronic rejection and poorer graft outcome.
-Acute AMR has a substantial impact on the long-term outcome and preoperative DSA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOi kidney transplantation.
-DSA MFI does not correlate with the chronicity and severity of pathology of AMR.
-Both late rejections and resistance to treatment are strongly associated with class II DSA, especially HLA-DQ, antibody.
-ABO-incompatible renal transplantation has an excellent one year graft
and patient survival.
– Patients going for ABO-I transplant who had SAB – HLA-DSA with MFI˃ 5000 did poorly despite desensitization.
-HLA and ABO incompatibility in combination patients should preferably go for swap transplantation.
_It is prospective study .
-Level II.
Well done
ABO incompatible transplant recipients with anti-HLA antibodies have higher risk of antibody mediated rejection (AMR) and graft loss.
This study was conducted to assess the effect of donor specific anti HLA sensitization on ABO incompatible kidney transplant recipients.
In this study, 66 patients underwent ABO incompatible kidney transplant, out of which 16 patients were sensitized. AMR was seen in 5 out of 66 patients (7.5%). In the sensitized group, AMR was seen in 18.75% (3 out of 16), while it was seen in 4% (2 out of 50) of non-sensitized patients.
Graft loss was seen in 2 out of the 3 sensitized patients with AMR and both had MFI >5000 before desensitization. The overall patient and graft survival at 1 and 4 years was 97% and 95% and 91.6% and 91.5%.
The conclusions derived include:
a) ABO incompatible transplants have excellent one-year patient and graft outcomes.
b) ABO incompatibility with anti HLA DSA positivity has poor graft outcomes, especially with baseline MFI > 5000.
c) Desensitization can reduce anti HLA antibodies, but there is increased risk of antibody rebound and consequent graft injury.
d) Patients with ABO incompatibility with anti HLA antibodies should be enrolled in a kidney paired donation transplant program.
This is a prospective cohort study.
Level of evidence: Level II
Well done
*ABO incompatible and positive crossmatch barrier was considered a contraindication to transplantation and has significant risk of hyper acute or acute AMR and graft loss due to the presence of blood group antibodies (iso-agglutinins) or HLA antibodies in the recipient.
*This study was done on 66 recipients with positive DSA before transplantation and received ABOi-KT.
*They were evaluated by CDC crossmatch, FCXM, SAB.
*Different desensitization protocols were applied aiming to remove current Ab ,modulate immune response, deplete B cell and reduced Ab production mainly with rituximab, plasmapheresis, triple immunosuppression 10 days before transplantation and IVIg
with induction with basiliximab or ATG.
*RESULTS
– ABO-I recipients who had anti-HLA antibodies MFI strength above 5000 did poorly despite desensitization with increased ABMR.
-Desensitization protocols allowed successful ABO-I renal transplantation, but there is increased ABMR and graft loss in sensitized patients with DSA.
-AMR could be due to either de novo antibody, (either anti-ABO antibody or HLA antibody) or
rebound of ant HLA DSA or anti ABO antibody.
– KT in patients with combined ABOi and HLAi had a similar incidence of acute AMR to that in exclusively HLAi patients, and was inferior to that in ABOi patients.
– a strong HLA-DSA at baseline was still a signifcant risk factor for acute AMR even when the ABOi group was included .
-preoperative DSA have signifcant association with poor graft outcomes than anti-blood group antibodies, even in ABOi kidney transplantation.
-ABO incompatible renal transplantation has excellent one year graft and patient survival.
Therefore HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for paired kidney exchange programme
This is Prospective study with control group, level of evidence II
Thank you Shereen
Q1. Summary
Rationale for ABO-incompatible kidney transplantation:
o Potentially increase the donor pool.
o Advancement in immune suppression and techniques that deplete anti HLA antibodies or prevent their further production (desensitization).
o Newer Immunosuppression that decrease risk of rejection.
Prerequisites for HLA i transplantation:
o Done till obtaining negative CDC cross match prior to transplant.
Materials and methods:
Patients were evaluated for DSA by CDC crossmatch, FCXM, Luminex SAB and lysate based solid phase crossmatch.
Desensitization protocol:
Rituximab 500 mg (RTX; dose – 375/mg/ m2) given, 10 to 12 days prior to transplant.
PEX, 2 to 10 sessions of were given. Recipient’s isoagglutinin titer
decreased below 1:8. Followed by low dose IVIG (100 mg/kg /dose) (after each PP session).
Postoperative PEX only if the anti-A, B isoagglutinin titer increased significantly above a level of 1:8 (within first two weeks of transplant) associated with
graft dysfunction with allograft biopsy suggestive of ABMR.
Induction: All the ABO-i KT patients received Basiliximab Or ATG if high-risk patients.
Maintenance: triple tacrolimus-based immunosuppression with MMF and prednisolone.
Discussion and summary:
o ABO-I transplant in those who had anti-HLA antibodies before desensitization had increased risk of ABMR, especially if MFI strength was more than 5000 by SAB assay.
o ABOi plus anti-HLA DSA positive represents a double hit and better to be avoided. Even with effective desensitization protocols, it still carries a high risk of rejection and graft loss.
o Best for highly sensitized recipients is KPD with much reduced cost.
Limitation: small sample size with short follow up
Q2 What is the type of the study and level of evidence?
Prospective cohort with control group, level II
Well done Mai
I’m not surprised, a high quality as usual
Thanks dear professor for your effort and continuous encouragement.
ABOi transplant increases the donor pool, but ABOi along with HLAi with preformed DSA is a very complex and very high risk transplantation from immunological point of view.
1.ABOi tx has good graft and patient survival.
2.ABOi tx with HLAi with DSA having mfi >5000 have poor graft and patient survival, even after desensitization process pre tx to lower down the mfi value is basically due to rebound of anti-HLA ab after tx leading to abmr and graft loss and due to high desensitization patient survival decreases to other morbidities.
Hence before overcoming dual immunological barrier, it is better to undergo kidney paired donation if feasible.
Prospective cohort study.
Well done
Donor specific anti HLA sensitization is associated with inferior short-term outcome in ABO- incompatible renal transplantation
Summarise the conclusion of this article:
This prospective cohort study included 66 cases with ABOi kidney transplant recipient with median age 34 and majority males 97%, induction with basiliximab in 62.5% of cases while ATG given in 37.5%
Majority received tacrolimus based conventional immunotherapy 98.4% only one case received cyclosporine based with MMF and prednisolone
All have negative crossmatch by CDC and FXCM, Luminex based solid phase assay for DSA with MFI cutoff value of 1000
Gel card method used for anti ABO titer measurements; IgM ABO ab titer done by neutral gel card while IgG ABO titer done by using AHG gel card with target level for transplantation of 1:8
Desensitization protocol of rituximab 375mg / m2 10-12 days, plasmapheresis 2-10 sessions alternate day with low dose IVIG 100mg/KG There is higher rate of graft loss and ABMR in the sensitized group 12.4 and 18.6 respectively in the first month post-transplant, the DSA rebound risk was higher in those with higher MFI prior to desensitization.
Conclusion of this study:
1- ABOi kidney transplant alone help in expanding the donor pool and favor one year graft and patient survival.
2- ABOi KTX plus anti-HLA DSA positive double hit better to be avoided even with desensitization carry high risk of rejection and graft loss.
3- In ABOi ktx the Pre transplant desensitization will reduce the anti HLA abs to the acceptable level but associated with high risk of early rebound after transplantation and AMR so better to avoid such combination and allocate for KPD program will be safer and less cost
Limitation: small sample size with short follow up
What is the type of this study and the level of evidence?
Prospective cohort with control group, level 2
You are the first one who notices the limitations of this study. Very impressed
This study included 66 patients who received ABO incompatible kidney transplantation who received desensitization protocol 10 to 12 days prior kidney transplant. Most of them were males (92.2% male, 7.8%female). CDC were negative for all patients at the time of transplant.
ABMR
patients undergoing ABO-I transplant who had anti-HLA antibodies before desensitization had high risk of ABMR. ABMR was seen in 7.5% of all patients. Non-sensitized group with MFI< 1000,ABMR was seen in 4.0% and in sensitized group MFI> 1000, ABMR was seen in 18.75% .
Graft loss within one month post-transplant
There is increased risk of graft loss in sensitized patients with DSA undergoing ABO-I transplant.
This was seen only in 2 patients due to ABMR in the sensitized group ( Both these patients had MFI > 5000 before desensitization which dropped to < 1000 at the time of transplant, but showed significant rebound after transplant)
Patient and graft survival
At one year patient survival was 97% and graft survival was 95%. At four years patient survival was 91.6% and graft survival was 91.5%.
So despite the fact that ABOi renal transplantation has excellent one year graft and patient survival, those with MFI >5000 have poor outcome. The combination of DSA positivity and ABO- incompatibility is associated with poor graft survival especially if MFI is > 5000 by SAB. Furthermore , there is a risk of rebound of anti-HLA antibodies after desensitization.
This is a single centre cohort study. It is not clear whether it is retrospective or prospective, so it could be level 2 or 3.
Well done
Donor specific anti HLA sensitization is associated with inferior short term
outcome in ABO- incompatible renal transplantation.
Abstract:
Sixty six patients were evaluated for donor specific anti HLA sensitization before they
received ABO incompatible kidney transplantation.
The desensitization protocol done.
Patients were evaluated for antibody mediated rejection (ABMR), donor specific anti HLA
sensitization, graft survival with anti HLA DSA positivity in ABO-incompatible kidney
transplant recipients.
1. Introduction:
ABO-incompatible renal transplantation has the potential to significantly increase the
donor pool.
great advancement in therapeutic options to remove and decrease production of anti-AB
and anti-HLA antibodies for treatment of acute or chronic antibody mediated rejection
and for reducing the risk of rejection episodes by modulating the immune response prior
to transplantation.
Patients who have positive PRA or patients with persistent weakly positive cross
matches may require therapy prior to transplant, lowing antibody titers (ABO and HLA)
so that crossmatch becomes negative per-transplant this reduces the risk of acute ABMR
post-transplant especially in anti-HLA sensitized ABOi transplant.
Materials and methods:
Patient selection AND Antibody test:
Patients were evaluated for DSA before they received ABO incompatible kidney
transplantation, BY CDC crossmatch, FCXM, SAB and lysate based solid phase
crossmatch.
Desensitization protocol:
Rituximab 500 mg (RTX; dose – 375/mg/ m2) which is administered, 10 to 12 days prior
to kidney transplant.
Plasmapheresis, 2 to 10 sessions of were given. Recipient’s isoagglutinins titer
decreased to a level below 1:8. Followed by IVIg (dose – 100 mg/kg per PP session
Postoperative plasmapheresis was given if the anti-A,B isoagglutinins titer increased
significantly above a level of 1:8 (within first two weeks of transplant) associated with
graft dysfunction with allograft biopsy suggestive of ABMR.
All the ABO-i KT patients received induction therapy:
Basiliximab
Or ATG induction in high-risk patients.
Results:
ABMR) was seen in five (7.5%) out of 66 patients.
Group-A (In non-sensitized) ABMR was seen in 4.0%.
Group-B (sensitized group) ABMR was seen in 18.75% with DSA positivity.
Graft loss within one month post-transplant was seen in 2 patients due to ABMR in the
sensitized group -B with Pretransplant positive DSA and in none in the non-sensitized
group-A both these two patients sensitized group -B had flow CM, SAB DSA and Lysate
CM positivity, with total MFI strength by SAB was above 5000, these two patients with
CDC and flow CM negative after desensitization and had SAB DSA MFI strength came
down to ≤1000.
Discussion:
Result shows that patients who were going for ABO-I transplant who had anti-HLA
antibodies before desensitization had increased ABMR.
Desensitization protocols effectively result in successful ABO-I renal transplantation, but
there is increased ABMR and graft loss in sensitized patients with anti-HLA antibodies.
Conclusion:
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor
graft survival especially at the time of immunological evolution if MFI strength was more
than 5000 by SAB assay.
Preoperative desensitization in ABO-I transplants can reduce anti HLA antibodies also to
acceptable levels but the anti-HLA antibodies can rebound after transplant and cause
ABMR with graft loss.
HLA and ABO incompatibility in combination is a high risk situation from immunological
point of view.
In such a situation patient should preferably go for swap transplantation.
Prospective cohort study.
level of evidence 11.
Excellent as usual
Prospective cohort study, level 2
Conclusion:
Short and sweet
summary of the article:
exposure of recipient to blood transfusion, previous transplant and pregnancy result in anti-HLA bodies formation .
there are two barrier for renal transplantation: ABO incompatibility and HLA incompatibility.
ABO i has potential increase the donor pool.
ABO i and positive cross match contraindicated as high risk for hyper acute or acute AMR and graft loss.
desensitization protocol modulate immune system as to lowering antibodies titre (ABO&HLA) to keep cross match negative pre transplant to reduce risk of ABMR pos
transplant.
new technique to evaluate histocompitability and anti HLA antibodies and ABO titre such as gel card for antibodies titre and rejection in solid phase anti HLA anti body assays improved and regulate the risk of rejection in presence of ABO and histocompatibilty.
in this study paients were evaluate for donor specific anti -HLA sensation by CDC crossmatch,flow crossmatch,SAB as to measure anti ABO and lysate based solid phase crossmatch and ABO i kidney transplant using gel card method to measure anti ABO titre keep the target 1:8 .
desensitisation protocol:
for ABOi transplant,rituximab,plasmapharsis followed by:
basilixmab, ATG( induction) and triple immunosupression thearpy
HLAi group has significance risk factor for acute AMR and and poor graft survival for acute AMR than ABO i.
Class 11 DSA antibodies espcillay HLADQ antibody associated with late rejection and resistance to treatment.
conclusion
ABOi renal transplant has excellent one year graft survival.
ABOi transplant and HLA DSA postive >500 has poor out come even with desensitization protocol .
rebound antiHLA antibodies even after desensitization which can cause ABMR with graft loss.
prospective cohort study.
level 11 evidence.
Well done
SUMMARY OF THE ARTICLE:
TYPE OF STUDY:
Prospective Cohort Study
Level-2 Evidence
Well done
Summarise the conclusion of this article
Anti HLA antibodies can develop due to exposure to HLA antigen resulting from previous blood transfusions, pregnancy and previous transplants. ABOi and positive cross match is a contraindication to transplantation due to high risk of hyper acute rejection and acute AMR. New diagnostic techniques like solid phase assays, desensitization protocols have made it possible to cross HLA and ABO incompatibility barriers.
CONCLUSION
ABO incompatible kidney transplantation ( ABOi-KT) has excellent 1 year graft and patient survivals i.e., 97% patient and graft survival 95% at one year.
Donor specific antibodies (DSA) of anti-HLA type is a risk factor for subclinical rejection, acute vascular rejection and chronic rejection which will lead to worst graft survival.
HLA and ABO incompatibility together are considered high risk for graft rejection , rendering Kidney exchange program a more favourable option
the hazardous effect of DSA on graft survival is even more than that cuased by anti- ABO antibodies.
DSA with mean fluorescence intensity (MFI) of more than 5000 by single antigen bead assay (SAB) in patients with ABOi-KT, will result in poorer graft outcome even with desensitization.
Desensitization protocols in ABOi before transplant can reduce anti HLA DSA levels but antibody rebound occurs after transplant causing ABMR and graft loss.
What is the type of this study and the level of evidence?
Prospective Cohort study
Level of evidence -II
Well done
Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO- incompatible renal transplantation.
It is a prospective study on 66 patients on dialysis evaluated before ABOi transplantation for HLA antibody by CDC , Flow cross match and single antigen bead assay.
All received desensitization protocol for ABO I transplantation in the form of (Rituximab 2 weeks before, PEX with IVIg and induction by basiliximab or ATG with steroid and maintained on tacrolimus based therapy).
By comparing non-sensitized group which was 50 patients with MFI ≤1000 on SAB assay to sensitized group (n = 16, MFI≥1000)
Showed that patient survival was 97% and graft survival was 95% at one year and at four years and patient survival was 91.6% and graft survival was 91.5% respectively.
There is increased ABMR and graft loss in sensitized patients with anti-HLA antibodies (DSA).
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
Prospective cohort study.
Level of evidence II.
Well done
The aim of the study ;
To evaluate the out come of combined HLA and ABO incompatibility kidney transplantation. So patients were evaluated for antibody mediated rejection (ABMR), donor specific anti HLA sensitization, graft survival with anti HLA DSA positivity in ABO-incompatible kidney transplant recipients.
Population;
Sixty six patients .
Patient selection;
Patients were evaluated for donor specific anti HLA sensitization before they received ABO incompatible kidney transplantation.
Antibody testing ;
To standardize results, HLA labs need to identify cut off (MFI) values for significance for Luminex based solid phase tests when compared with traditional CDC and flow cross match results .
Gel card method was used to measure anti ABO titers.
IgM ABO antibody titers are done by neutral gel cards on serially diluted patient serum.
IgG ABO antibody titers were done using AHG gel cards. Anti- Blood group titer of 1:8 is the target.
The ABO titration was performed before and after every session of PP/ IVIg .
Desensitization Protocol ;
The desensitization protocol for ABO incompatible transplant includes infusion of 500 mg of Rituximab (RTX; dose – 375/mg/ m2) which is administered, 10 to 12 days prior to kidney transplant (KT).
2 to 10 sessions of plasmapheresis were given (depending on the anti- ABO titer) performed over 2 to 14 days before surgery until a recipient’s isoagglutinin titer decreased to a level below 1:8.
Postoperative plasmapheresis was given if the anti-A,B isoagglutinin titer increased significantly above a level of 1:8 (within first two weeks of transplant) associated with graft dysfunction with allograft biopsy suggestive of ABMR.
Immunosuppressant protocol;
All the ABO-i KT patients received induction therapy with either Basiliximab (an anti-CD25 monoclonal antibody) (on day 0 and 4) or Rabbit anti- thymocyte globulin (ATG) induction in high-risk patients was given in a total dose of 3–4.5 mg/kg on in three doses given day zero and then alternate days post-transplant.
The patients received triple sequential immunosuppression – mycophenolate mofetil (MMF; dose – 1500–2000 mg/day) and tacrolimus (dose – 0.1 mg/kg daily; adjusted to a 12 h, trough levels of 8–12 ng/ ml) and low dose steroids prednisolone were started 10 days prior to surgery.
The study result ;
Anti HLA DSA positivity with ABO- incompatibility is associated with poor graft survival.
Conclusion;
Anti HLA DSA positivity with ABO- incompatibility in combination is associated with poor graft survival especially at the time of immunological evolution if MFI strength was more than 5000 by SAB assay.
HLA and ABO incompatibility in combination is a high risk situation from immunological point of view. In such a situation patient should preferably go for swap transplantation.
What is the type of this study and the level of evidence?
prospective Cohort study
Level of evidence
Level 2
Well done
This is prospective cohort study and level II evidence
It is pre-transplant DSA and NOT transplant DSA
Thank you