Live Donor Renal Transplantation in India: Outcome and Comparison of Different Induction Therapies with a Focus on Gender Bias in Live Donor Renal Transplantation

BACKGROUND: As of 2014, an estimated 9% of the global population aged 18+ years was affected by diabetes. The World Health Organization (WHO) also estimated around 2.5% of deaths were attributed to diabetes in 2012 and more than 80% of those deaths occurred in low-middle income countries. It is apparent that diabetes and its complications are becoming a global issue as an increasing common, preventable, non-communicable disease. Along with cardiovascular disease, blindness, and neuropathy, end stage renal disease (ESRD) is one of the serious complications that can develop as a result of diabetes. Diabetes is the leading cause of ESRD in both developed countries like the United States and developing countries like India. India is a particularly interesting country to observe given their vast population base, rapid growing economy, genetic predisposition to diabetes and increased insulin resistance. It is estimated that 100,000 patients develop ESRD each year in India with diabetes as the main underlying cause (44% of all ESRD cases). Once a patient develops ESR, renal replacement therapy (RRT) is required to sustain life. RRT consists of three options: 1) hemodialysis (HD), 2) peritoneal dialysis (PD), or 3) renal transplant (RT). Of the three options, renal transplant is considered the best in terms of quality of life and cost effectiveness, but only about 5% of Indian patients with ESRD end up receiving RT. Most RT in India come from living donors rather than cadaveric donors like in the United States. Induction therapy with interleukin-2 receptor alpha chain (IL2-RA) is recommended as a first line agent in LRT however comparative outcomes of induction therapy remains controversial in Indian LRT population. OBJECTIVE: To evaluate patient survival and allograft function in LRT with a specific focus on the Indian population between 2010 and 2014 and to access the impact of different induction therapies on the outcomes of Indian LRT patients. METHODS: A single center (Medanta Medicity, Gurgaon, India) dataset was retrospectively studies for patients receiving LRT from 2010 to 2014 (N=901) to compare effectiveness of IL2-RA to other induction options (no-induction and rabbit anti-thymocyte globulin [r-ATG]). IL2-RA and no induction were chosen for immunologically low risk patients. R-ATG was primarily given to the recipient with PRA>20% and HLA mismatch >5 antigen out of 6. Patient paper charts were analyzed for dates not included in the Medanta database which included follow-up dates with corresponding creatinine levels (at 3 months, 6 months, 1 year, and last follow up), date and type of rejection if applicable, graft loss and death. Patients included in the data set had their last follow up at Medanta within the last 6 months from the time data was collected. The patient data was used to calculate rejection rate, graft failure, and hazard ratio (HR) for overall graft failure. The main outcomes were the risk of acute rejection at one-year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. RESULTS: Similar Kaplan Meier curves for overall graft survivals were observed among induction categories. Rejection rate was higher in no-induction and IL2-RA groups (~25%) compared to r-ATG induction. On univariate Cox analysis, compared to no-induction therapy, overall allograft failure was similar among induction categories. Most of the rejections were borderline or Banff Type I acute cellular rejections. CONCLUSION: Compared to no-induction therapy, IL2-RA induction was not associated with better outcomes in Indian LRT recipients. R-ATG appears to be an acceptable and possibly preferred induction alternative for IL2-RA in high rejection risk Indian patients.