Introduction: Induction immunosuppression therapy plays a significant role in the prevention of acute rejection in renal transplantation. This study aimed to evaluate the effectiveness and safety of rabbit anti-thymocyte globulin (rATG) used as induction immunosuppression in Indian patients undergoing renal transplantation. Patients and Methods: RISE was a multicenter (n = 20), prospective observational cohort study of patients aged ≥ 18 years undergoing a first or repeat renal transplant and receiving rATG as part of the routine management practice. Twelve-month acute rejection was evaluated as a primary endpoint. Results: A total of 325 patients were enrolled, of which 313 patients received at least one dose of rATG with a mean (standard deviation [SD]) duration of induction therapy of 2.07 (1.33) days. The mean (SD) cumulative rATG induction dose was 2.6 (1.5) mg/kg. The mean (SD) glomerular filtration rate was 64.59 (19.57) mL/min/1.73 m2 at 6 months and 64.93 (20.26) mL/min/1.73 m2 at 1 year. The incidence of acute rejection at 1 year was 7.7% (n = 23). Graft rejection at 6 months was observed in 6.7% (n = 20) patients and an average time to first graft rejection of 5.4 and 10.3 months at 6 and 12 months, respectively. In total, 342 adverse events (AEs) were reported (n = 154, 49.2%) after 12 months, of which 11 events were related to the rATG treatment. Pyrexia was the most commonly reported serious adverse event (n = 10, 3.2%). Seven deaths were reported during the study. Conclusions: The study revealed the effectiveness and safety of rATG induction therapy in the Indian context as expected based on the data from randomized clinical trials. Trial Registration Number: CTRI/2017/09/009/009700.

Graft loss and rejections (acute/chronic) continue to remain important concerns in long-term outcomes in kidney transplant despite newer immunosuppressive regimens and increased use of induction agents. Global guidelines identify the risk factors and suggest a framework for management of patients at different risk levels for rejection; however, these are better applicable to deceased donor transplants. Their applicability in Indian scenario (predominantly live donor program) could be a matter of debate. Therefore, a panel of experts discussed the current clinical practice and adaptability of global recommendations to Indian settings. They also took a survey to define risk factors in kidney transplants and provide direction toward evidence- and clinical experience-based risk stratification for donor/recipient and transplant-related characteristics, with a focus on living donor transplantations. Several recipient related factors (dialysis, comorbidities, and age, donor-specific antibodies [DSAs]), donor-related factors (age, body mass index, type – living or deceased) and transplantation related factors (cold ischemia time [CIT], number of transplantations) were assessed. The experts suggested that immunological conflict should be avoided by performing cytotoxic cross match, flow cross match in all patients and DSA-(single antigen bead) whenever considered clinically relevant. HLA mismatches, presence of DSA, along with donor/recipient age, CIT, etc., were associated with increased risk of rejection. Furthermore, the panel agreed that the risk of rejection in living donor transplant is not dissimilar to deceased donor recipients. The experts also suggested that induction immunosuppression could be individualized based on the risk stratification.

Large-scale Indian data on the use of anti-T-lymphocyte globulin (ATLG) (Grafalon®) as induction therapy in kidney transplantation (KT) patients is lacking. The aim of this study was to determine the 1-year patient and graft survival outcomes with the use of ATLG as induction regimen in KT. In a prospective, multicentric, observational study, adult patients who underwent ABO-compatible KT and had received ATLG as a part of induction were included in the study. The primary outcome measure was overall survival and death-censored graft survival at 12 months. The primary safety outcome was assessed by development of infectious complications and graft rejection. In total, 359 patients were included in this study. The mean age was 42.77 ± 12.30 years and 83% were male. The average ATLG dose per patient was 6.2 ± 2.2 mg/kg whereas average cumulative dose per patient was 389.6 ± 149.8 mg. The rate of graft dysfunction was 13.4% of patients and 6.7% had biopsy-proven acute rejection (BPAR). There were a total of 12 (3.3%) deaths and one graft loss. Overall survival and death-censored graft survival at 12 months were 96.65% and 99.44%, respectively. The rate of infections was 13.6% with urinary tract infections being most common. ATLG at an average dose of 6 mg/kg is an effective and safe induction regimen immunosuppressant for ABO-compatible KT with favourable impact on survival and graft function in Indian patients.

OBJECTIVES Evidence on living donor kidney transplant procedures when both the donor and recipient have had a history of COVID-19 infection is scarce. MATERIALS AND METHODS We retrospectively explored the protocol, outcomes, and follow-up of 64 donors and recipients of living donor kidney transplant who had recovered from COVID-19. This was a multicenter (n = 12) study from India that included transplants between October 29, 2020, and December 1, 2021. Induction and immunosuppression regimens forthose with different severities of COVID-19 were similar to standard practice. RESULTS COVID-19 clinical severity ranged from asymptomatic/mild (not requiring oxygen therapy) in 49 recipients (77%) and 63 donors (95.4%) and moderate/severe (requiring oxygen therapy) in 15 recipients (23%) and 1 donor (4.6%). Mean wait time±SEM (SD)from firstdocumentednegative reverse transcriptase-polymerase chain reaction testto surgery for recipients and donors was 90.9 ± 9.27 (74.1) and 47 ± 4.5 (29.2) days, respectively. Six episodes (9.3%) of biopsy-proven acute rejection were reported at follow-up of 214 ± 14.8 (119) days and median of 227 (interquartile range, 109-309) days. The locally weighted scatter plot smoothing curve for creatinine during follow-up in donor-recipients pairs showed no trends of increased creatinine in the context of wait time from COVID-19 to transplant surgery. No graft loss, death, reactivation/reinfection, and complications related to surgery or COVID-19 were reported. CONCLUSIONS Our report showed excellent outcomes and follow-up data of living donor kidney transplant in recovered donor-recipient pairs with the standard immunosuppression protocol. To our knowledge, this is the first and the largest study of donor-recipient living donor kidney transplant pairs when both donors and recipients had prior COVID-19.

Background. Limited data exist on the incidence and outcome of early coronavirus disease 2019 (COVID-19) in kidney transplantation recipients (KTR). Methods. A retrospective multicenter research study was conducted across 12 centers in India. We explored the symptomatology, demographic, laboratory findings, and outcome of COVID19 within 30 days of transplantation. The outcome was compared with the overall KTR and waitlisted patients acquiring COVID-19. Results. The incidence of early COVID-19 was 2.6% (n = 22) for the cumulative 838 renal transplants performed since nationwide lockdown in March 2020 until May 2021. Overall, 1049 KTR were diagnosed with COVID-19 and 2% of those had early COVID-19. The median age of the early COVID-19 cohort was 43 (31-46) years. COVID-19 severity ranged from asymptomatic (18.2%), mild (59.1%), moderate (9.1%), and severe (13.6%). Among clinical symptoms, dyspnea and anosmia were frequent, and in laboratory parameters, neutrophil lymphocyte ratio, high-sensitivity C-reactive protein, and D-dimer were higher in patients requiring oxygen. The mortality in early COVID-19 was not higher than overall KTR (4.5% vs 8.5%; P = 1). COVID19 severity (23.9% vs 15.7%; P = .0001) and mortality (15.5% vs 8.5%; P = .001) among waitlisted patients (n = 1703) were higher compared with overall KTR. Conclusions. We report higher burden of COVID-19 in waitlisted patients compared with KTR and a favorable outcome in early COVID-19 in KTR. Our report will help the transplant physicians in dealing with the ongoing dilemma of halting or resuming transplantation in the COVID-19 era.

BackgroundThe effect of coronavirus disease 2019 (COVID-19) on a developing nation is sparsely reported and, more importantly, the discrepancies in public and private sectors are underexplored.MethodsWe retrospectively investigated the data on the effect of COVID-19 on renal transplantation between 2019 and 2020 in a nationwide analysis from 8 public and 10 private sector hospitals of India.ResultsOn comparing the yearly data, the number of living-related transplants and deceased donor transplants declined by 48% (2610 vs 1370) and 49% (194 vs 99), respectively. The outpatient numbers and in-center admissions decreased by 40.4% (616,741 vs 367,962) and 30.8 % (73,190 vs 49,918). respectively. There was no increase in the number of renal or graft biopsies in the COVID-19 era. The number of waitlisted patients on hemodialysis was higher in public (304,898 vs 338,343) when compared with private (163,096 vs 150,292) in the last 2 years. Similarly, the number of waitlisted patients on peritoneal dialysis (4655 vs 3526) was higher in the public sector compared with private sector (932 vs 745). The decline in living transplants during the pandemic was higher in public sectors (58%) compared with the private (49%). However, the decline in deceased donation was higher in private (57.9%) relative to public (50.6%).ConclusionsCOVID-19 has adversely affected the transplantation activities across the Indian transplantation centers, with a disproportionately higher impact on waitlisted patients in public sector programs. A sound prioritization of health care resources is mandated to safeguard the most deprived and high-risk waitlisted patients during the pandemic.

Renal diseases like chronic kidney disease (CKD) and end-stage renal disease (ESRD) are a major healthcare burden in developing countries like India. Kidney transplantation is considered to be the most viable treatment option for such patients. In comparison to dialysis, renal transplantation is associated with reduced mortality and improved quality of life. However, a major challenge experienced in transplant procedures is transplant rejection. Four virtual advisory board meetings involving 30 nephrology experts were conducted to discuss the current therapeutic landscape of kidney transplant rejection in India and subsequent practice-based insights of the experts were garnered. The experts concurred on the need for appropriate screening including immunological profiling, diagnosis, and management of candidates for transplantation. While immunosuppressive therapy and strategies like plasmapheresis, intravenous immunoglobulin, corticosteroids, and rituximab have been well established in the treatment of transplant rejection, novel and emerging treatment modalities like interleukin-6 antagonists, imlifidase or complement inhibitors have shown promise and should be considered. Increased awareness among physicians about the development of newer immunosuppressive regimens with lower side effects that may improve long-term outcomes of kidney transplantation is warranted.