Introduction:
Kidney transplantation provides a considerable survival advantage compared to hemodialysis in patients with end-stage kidney disease. Thus, the organ demand is continuously growing while a considerable gap exists between organ availability and waiting listed patients, although the pool of deceased donors has been successfully expanded with donation after circulatory death or kidneys from extended criteria donors. Kidney transplant from living donor offers a superior survival of both patient and graft than transplant from deceased donation and is the most effective way to expand the donor pool. However, immunologic barriers frequently pose limitations to this transplant. These barriers are mainly represented by preformed anti-human leukocyte antigen (HLA) antibodies and ABO system antibodies, which can cause hyperacute rejection. For a long time, ABO incompatible (ABOi) living donor kidney transplantation was contraindicated, due to its immunological impediment based on the presence of isohemagglutinins, natural antibodies reacting with non-self ABO antigens. Nevertheless, in 1987, Alexandre et al reported the first results of their pioneering program of ABOi living donor kidney transplantation. They laid the basis for the recipient preconditioning, commonly termed desensitization, a combination of treatments and procedures aiming at reducing isohemagglutinins levels. Nowadays, preconditioning consists in the combination of immunosuppressive agents, administered before transplantation (ie, rituximab) to prevent the production of new antibodies, apheresis techniques and maintenance immunosuppressants. No consistent data regarding the non-inferiority or superiority of individual regimens are currently available, due to the paucity of randomized controlled trials. Outcomes in ABOi kidney transplantation (ABOiKT) have markedly improved over the years. Recently, a meta-analysis including 21 studies reporting the outcome of ABOi kidney transplant by comparing ABO compatible (ABOc) has revealed that there is no difference in terms of graft failure, biopsy-proven acute rejection and patient survival [9]. In their consistent series including 62 ABOi kidney transplant, Barnett et al reported a three-year graft survival of 98.4%, a T-cell mediated rejection rate of 27.4% and an antibody mediated rejection rate of 4.8% at one-year post transplant. No statistically significant differences were found between the ABOi group and the group of ABOc kidney transplant performed in the same time period and in the same Transplant Center. Anecdotal experience suggests that approximately 200–250 ABOiKT are performed annually in India. However, the protocols for working up, desensitization are not uniform and clinical outcomes vary significantly. With more centers wanting to start ABOiKT, there is a need to standardize the clinical practice and protocols and provide guidance to new centers on ABOiKT in India. There is a concern about the right method of Ab detection, acceptable Ab titer at the time of transplant, desensitization and immunosuppression protocol, need for posttransplant monitoring and desensitization and diagnosis and treatment of Ab-mediated rejection. Desensitization protocols have allowed for successful transplantation of kidney allografts across the ABO blood group barrier. Pioneering centers in ABO-incompatible kidney transplantation have published patient and graft survival rates comparable to ABO-compatible transplantations. These reassuring outcomes combined with long waiting times for deceased-donor kidneys and the shortage of available living donors have led to a broader implementation of ABO-incompatible transplantation in India. Last few decades have witnessed significant improvement in the outcomes of ABOi kidney transplant with the advent of newer preconditioning protocols and improved maintenance immunosuppression. However, there are very few publications of ABOi kidney transplants from the developing world. In present study, we thus aimed to evaluate the clinical outcomes in ABO Incompatible Renal Transplant in Indian sun continent.
Methods:
Aims and objectives Aim To evaluate the clinical outcomes in ABO Incompatible Renal Transplants Objectives Primary To study the feasibility of ABO incompatible renal transplant for patients who do not have a compatible donor. To study the clinical outcomes with respect to graft function at 1/ 3/ 6/ 12 months. To study correlation between ABOi titres and clinical outcomes. To evaluate the safety and efficacy of Basiliximab and Anti-Thymocyte Globulin as an induction protocol along with Rituximab for ABOi Renal Transplant. Secondary To study outcome of Biopsy Proven Rejection and institute appropriate treatment. To study whether there is an increased risk of infection in ABOi Renal Transplant. To study death censored graft function. Study design: Single centre prospective hospital based observational study. Study site: The study was conducted in the Department of Nephrology, Apollo Hospital, Navi Mumbai in order to ascertain the clinical outcomes in patients undergoing ABOi Renal Transplant. Study population : Both, male and female patients undergoing ABO incompatible renal transplants above the age group of 18 years at Apollo Hospitals, Navi Mumbai. Study period : 15 months Ethical clearance: From the Institutional Ethics Committee was obtained. Subjects : Inclusion criteria Adults ( >18 years ) undergoing ABOi renal transplant during the study period. Patients who give written informed consent. Exclusion criteria Repeat renal transplantation. ABO Compatible Renal Transplant. Patients who refuse to give written informed consent. Methods The study was initiated on approval from the Institutional Ethics Committee. Eligible patient were included in the study only after obtaining written informed consent. The detailed history and clinical examination was done as per the predesigned proforma attached herewith. Pre-Transplant evaluation was done as per standard ABOi Renal Transplant guidelines. Preconditioning protocol of standard ABOi Renal Transplant guidelines was followed. Clinical outcomes of ABOi Renal Transplant were noted in the predesigned case record forms. The patients were followed up periodically for the period of 1 year and outcomes were documented. Statistics Sample size calculation was done using SAS9.2 for new study. Efficacy variable used was One-year graft survival of patients in ABO-incompatible renal transplant. Null Hypothesis (H0) included One-year graft survival of patients in ABO-incompatible renal transplant of 96.0% while Alternative Hypothesis (H1) considered Anticipated One-year graft survival of patients in ABO-incompatible renal transplant of 85.0 %. Sample size calculated was 33, (Power= 80%, Alpha=0.05). With the anticipated loss to follow up of 20% , total Sample size of 40 was decided. Data was analysed using SPSS V15.0 (Statistical Package for Social Sciences, Version 15.0) package. Data was calculated as Mean , SD and Number for continuous data and Number and Percentage for categorical data. Comparison of means of 2 groups was carried out by Student’s unpaired t test for numerical normal data and by Mann Whitney U test for abnormal data. Fisher Exact Probability tests was applied to compare percentages for categorical data between 2 groups. Chi square test was applied to compare percentages of more than 2 groups. Kaplan Meier Survivor curve and survival analysis was carried out. All statistical tests will be two tailed. Alpha (α) Level of Significance will be taken as P<0.05.
Results:
ABO incompatible renal transplant was done in for patients who did not have a compatible donor. The clinical outcomes with respect to graft function at 1/ 3/ 6/ 12 months revealed post transplant perinephric hematoma in 4 (10%), urinary tract infection in 11 (27.5%), cytomegalovirus (CMV) infection in 2 (5%), BK polyoma virus infection in 4 (10%), and pneumonia in 5 (12.5%) patients. None developed Pneumocystis Carini Pneumonia. Graft rejection was seen in 3 (7.5%) patients while 2 (5%) patients succumbed to death. The correlation between ABOi titres and clinical outcomes was evaluated along with the safety and efficacy of Basiliximab and Anti-Thymocyte Globulin as an induction protocol along with Rituximab for ABOi Renal Transplant. Three patients with biopsy proven rejection were analysed and appropriate treatment was instituted.
Conclusions:
Outcomes in ABOi kidney transplantation (ABOiKT) are promising with no difference in terms of graft failure, biopsy-proven acute rejection and patient survival as compared to ABO compatible (ABOc) renal transplant.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.