Long-term Kidney Transplant Survival Across the Globe.

BACKGROUND: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. METHODS: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. RESULTS: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. CONCLUSIONS: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

A Multicenter Retrospective Cohort Study on Management Protocols and Clinical Outcomes After ABO-incompatible Kidney Transplantation in India.

BACKGROUND: There is no robust evidence-based data for ABO-incompatible kidney transplantation (ABOiKT) from emerging countries. METHODS: Data from 1759 living donor ABOiKT and 33 157 ABO-compatible kidney transplantations (ABOcKT) performed in India between March 5, 2011, and July 2, 2022, were included in this retrospective, multicenter (n = 25) study. The primary outcomes included management protocols, mortality, graft loss, and biopsy-proven acute rejection (BPAR). RESULTS: Protocol included rituximab 100 (232 [13.18%]), 200 (877 [49.85%]), and 500 mg (569 [32.34%]); immunoadsorption (IA) (145 [8.24%]), IVIG (663 [37.69%]), and no induction 200 (11.37%). Mortality, graft loss, and BPAR were reported in 167 (9.49%), 136 (7.73%), and 228 (12.96%) patients, respectively, over a median follow-up of 36.3 mo. In cox proportional hazard model, mortality was higher with IA (hazard ratio [HR]: 2.53 [1.62-3.97]; P < 0.001), BPAR (HR: 1.83 [1.25-2.69]; P = 0.0020), and graft loss (HR: 1.66 [1.05-2.64]; P = 0.0310); improved graft survival was associated with IVIG (HR: 0.44 [0.26-0.72]; P = 0.0010); higher BPAR was reported with conventional tube method (HR: 3.22 [1.9-5.46]; P < 0.0001) and IA use (HR: 2 [1.37-2.92]; P < 0.0001), whereas lower BPAR was reported in the prepandemic era (HR: 0.61 [0.43-0.88]; P = 0.008). Primary outcomes were not associated with rituximab dosing or high preconditioning/presurgery anti-A/anti-B titers. Incidence of overall infection 306 (17.39%), cytomegalovirus 66 (3.75%), and BK virus polyoma virus 20 (1.13%) was low. In unmatched univariate analysis, the outcomes between ABOiKT and ABOcKT were comparable. CONCLUSIONS: Our largest multicenter study on ABOiKT provides insights into various protocols and management strategies with results comparable to those of ABOcKT.

De novo Donor-specific Anti-human Leukocyte Antigen Antibody and Its Outcome in Pediatric Renal Transplant Recipients: A Single-center Experience in India.

Development of de novo donor-specific anti-HLA antibody (dnDSA) is associated with poor graft survival in adults. However, there is a paucity of data about its prevalence and outcome in Indian children. We retrospectively assessed the proportion and spectrum of dnDSA and its outcome on antibody-mediated rejection (ABMR) and graft function. Children ≤18 years who were transplanted between November 2016 and October 2019 were included in this study. Pretransplant donor-specific antibody (DSA) was screened by complement-dependent cytotoxicity, flow cytometry crossmatch, and single antigen bead (SAB) class I and II by Luminex platform. Either antithymocyte globulin or basiliximab was used as induction. Tacrolimus, mycophenolate, and prednisolone were used for the maintenance of immunosuppression. SAB screening was done at 1, 3, 6 months, and yearly in seven children and at the time of acute graft dysfunction in eight. Mean fluorescence intensity ≥1000 was considered positive. Protocol biopsies were done at 3, 6, and 12 months and annually thereafter in seven children. Fifteen children, all males with a median age (interquartile range) of 13 years (11; 15.5) were analyzed. Only one child had pretransplant DSA who developed dnDSA posttransplant. Overall, 8 (53%) developed dnDSA over a median follow-up of 18 months. Seven (87%) had Class II, one Class I and 3 (37%) both Class I and II. Six had dQ and two had DR. All children with dnDSA had ABMR, of these two had subclinical rejection. DSAs persisted despite treatment, though graft function improved. Children with DSA and ABMR had lower graft function than those without DSA. The proportion of dnDSA was high in our study, majority against DQ. The detection of dnDSA prompted early diagnosis and treatment of ABMR.

Kidney paired donation in developing countries: A global perspective.

Purpose of review: We review the key principles of kidney paired donation (KPD) and discuss the status and unique considerations for KPD in developing countries. Recent findings: Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices. Summary: KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need world-wide.

Social Media and Organ Donation: Pros and Cons.

Shortage of organ donors is the most important obstacle standing in the way of lifesaving organ transplantation in a myriad of patients suffering from end-stage organ failure. It is vital that the transplant societies and associated appropriate authorities develop strategies to overcome the unmet needs for organ donation. The power of prominent social media (SoMe) platforms such as Facebook, Twitter, and Instagram, which reach millions of people, can increase awareness, provide education, and may ameliorate the pessimism toward organ donation among the general population. Additionally, public solicitation of organs may be helpful for waitlisted candidates for organ transplantation, who cannot find a suitable donor among near relations. However, the use of SoMe for organ donation has several ethical issues. This review attempts to highlight the advantages and limitations of using social media in the context of organ donation for transplantation. Some suggestions on the best utilization of social media platforms for organ donation while balancing ethical considerations have been highlighted here.

Outcomes of Living Donor Kidney Transplant After SARS-CoV-2 Infection in Both the Donor and the Recipient: A Multicenter Study.

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.

COVID-19 Vaccination in Solid-Organ Transplant: A Real-World Multicenter Experience.

OBJECTIVES: India ranks third globally in organ procurement and transplant and has the second highest COVID-19 incidence rate, but data regarding COVID-19 vaccination in solid-organ transplant patients are scarce. MATERIALS AND METHODS: We created a cross-sectional, anonymous, online questionnaire and sentinvitations to several transplant centers in India. We surveyed vaccine mandates, immunization coverage and side effects, administration timing, infection severity among solid-organ transplant recipients, and booster dosage recommendations. RESULTS: The survey results showedthat vaccinepolicy is heterogeneous among centers; vaccination is voluntary at some centers (44.7%), but some centers have established COVID-19 vaccination as a requirement for transplant candidates (44.6%). CoviShield was the most common vaccine administered (89.3%), and more than 50% of transplant recipients and donors were fully vaccinated. Survey results showed that the pretransplant wait time after full vaccination (both doses) is 2 to 4 weeks (48.9%), and the optimal time for vaccination after transplant is 3 to 6 months (59.3%). For vaccinated transplant patients, 89.4% of respondents reported an incidence rate for posttransplant breakthrough infection of less than 25%. For unvaccinated patients, 38.3% ofrespondents reported a 25% to 50% incidence rate of posttransplant COVID- 19 infection. Booster doses are recommended at many transplant centers in India, as reported by 89.4% of survey respondents. CONCLUSIONS: The results of the survey suggested that there are no substantial safety concerns Future targets should include increasing efficacy and increasing booster doses of the COVID-19 vaccine.

A Narrative Review COVID-19 in Solid-Organ Transplantation: Real-World Evidence From India.

Worldwide, India ranks number 2 and 3 for COVID-19 burden and absolute transplant numbers, respectively. Here, we summarized our single and multicenter Indian studies on solid-organ transplant during the COVID-19 pandemic. During the pandemic, solid-organ transplants declined 40% to 50%. The mortality rate in COVID-19-positive kidney transplant recipients (11.6%) was lower in India compared with the developed world during the first wave and lower compared with maintenance hemodialysis patients (13% to 38%) but significantly higher compared with the nonimmunosuppressed general population (1% to 3%) in India. We contributed to National Organ and Tissue Transplant Organization transplant-related guidelines to increase safety and access to solid-organ transplant. We reported the safety and feasibility of remdesivir (n = 57) and convalescent plasma therapy (n = 10) in kidney transplant recipients. We reported 100% patient and graft survival without any complications related to COVID-19 in a large cohort of kidney transplant recipients who recovered from COVID-19 (n = 372) and a large cohort of kidney transplant recipients of living donors (n = 31) who recovered from COVID-19 without any change in induction and maintenance immunosuppression. COVID-19 disease severity and mortality in the second episode (reoccurring infection) was higher (46%) compared with the first episode (11.6%). There was 4.4% incidence of COVID-19-associated mucormycosis in kidney transplant recipients with mortality of 46% in the second wave. We reported COVID-19 vaccine safety with suboptimal efficacy in kidney transplant recipients and dialysis patients compared with the general population. Our report suggested that transplant with carefully selected COVID-19-recovered donors and patients may be feasible and safe, at least over the short term. Continued research is needed on vaccine efficacy, booster doses, and long-term follow up sequelae.

COVID-19 in Hemodialysis Patients: Experience from a Western Indian Center.

Introduction: Chronic kidney disease patients on hemodialysis (CKD-5D) are among the worst hit by the coronavirus disease 2019 (COVID-19) pandemic. Need to travel for dialysis, comorbidities, and immunosuppressive state put them at risk of severe disease and poor outcomes. We report our experience of COVID-19 in a cohort of CKD-5D from a public sector tertiary-care center from western India. Material and Methods: We retrospectively analyzed the records of 58 CKD-5D patients with confirmed COVID-19 admitted to our COVID-19 hospital. Suspected COVID-19, acute kidney injury (AKI), or AKI on CKD were excluded. We studied the clinical, demographic, radiological, and laboratory profiles; treatment; and outcomes of the patients. We assessed the potential clinical and laboratory parameters to predict mortality. Results: The mean age of the patients was 48.7 ± 16.9 years, with 55% males. Comorbidities included hypertension (65%), diabetes (19%), and cardiovascular disease (15.5%). The presenting features included fever (69%), respiratory distress (50%), upper respiratory symptoms (36%), and diarrhea (13%). Five (8.6%) were asymptomatic. Bilateral infiltrates on chest imaging were the commonest radiological pattern. The patients were managed with oxygenation, hydroxychloroquine, steroids, anticoagulation, remdesivir, and favipiravir. Twenty-two (37.9%) patients died, predominantly due to respiratory failure. Disease severity and C-reactive protein (CRP) above 175 mg/L at admission were the only parameters predictive of mortality. Conclusion: CKD-5D patients with COVID-19 were less likely to present with the classical syndrome of fever and respiratory distress compared with reports from the general population and had higher mortality. Only disease severity and high CRP (>175 mg/L) were predictive of mortality in our cohort.

Safety and Tolerability of Remdesivir in Patients with End-stage Renal Disease on Maintenance Hemodialysis.

Introduction: The use of remdesivir is not recommended in patients with end-stage renal disease (ESRD) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless potential advantage offset disadvantage due to limited safety data. Our objective was to assess the safety of remdesivir in patients with end-stage renal failure and evaluate the outcome of this vulnerable group. Methodology: We carried out a retrospective observational study in dialysis-dependent ESRD patients with SARS-CoV-2 infection who received a standard 5-day course of remdesivir (powder form) from June 2020 to December 2020. Oxygen requirement, hemogram, inflammatory markers, and liver function tests before and after remdesivir treatment were compared. Result: We found thirty-nine such patients with mean age of patients 58.79 ± 12.13 years. Diabetes mellitus, hypertension, and cardiac diseases were present in 58.97, 87.17, and 23.07% of patients, respectively. Mean oxygen saturation on admission was 85.41% (±7.73). There were no events of hepatotoxicity, altered behavior, or infusion reaction. There was statistically significant improvement in total leukocyte count, absolute lymphocyte counts, and C-reactive protein (p value <0.001, 0.01, and 0.02, respectively) post remdesivir treatment. A total of 60% of patients had improved oxygenation while 13% of patients had no change in oxygen requirement after completion of remdesivir course. Mortality in our study was 28.21%. We did not find any significant benefit of early remdesivir administration (3-6 days of illness) on mortality or days of hospitalization. Conclusion: The use of remdesivir in end-stage kidney disease is safe. Improvement in oxygenation was significant when baseline oxygen requirement was less. It requires prospective controlled trials with larger population to assess its impact on mortality. How to cite this article: Shah MK, Parikh M, Prajapati D, Kute VB, Bhende P, Prajapati A, et al. Safety and Tolerability of Remdesivir in Patients with End-stage Renal Disease on Maintenance Hemodialysis. Indian J Crit Care Med 2022;26(5):619-625.

Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper.

Organ donation following circulatory determination of death (DCDD) has contributed significantly to the donor pool in several countries. In India, majority of deceased donations happen following brain death (BD). While existing legislation allows for DCDD, there have been only few reports of kidney transplantation following DCDD from India. This document, prepared by a multidisciplinary group of experts, reviews international best practices in DCDD and outlines the path for DCDD in India. Ethical, medical, legal, economic, procedural, and logistic challenges unique to India have been addressed. The practice of withdrawal of life-sustaining treatment (WLST) in India, laid down by the Supreme Court of India, is time-consuming, possible only in patients in a permanent vegetative state, and too cumbersome for day-to-day practice. In patients where continued medical care is futile, the procedure for WLST is described. In controlled DCDD (category-III), decision for WLST is independent of and delinked from the subsequent possibility of organ donation. Families that are inclined toward organ donation are explained the procedure including the timing and location of WLST, consent for antemortem measures, no-touch period, and the possibility of stand-down and return to the intensive care unit (ICU) without donation. In donation following neurologic determination of death (DNDD), if cardiac arrest occurs during the process of BD declaration, the protocol for DCDD category-IV has been described in detail. In DCDD category-V, organ donation may be possible following unsuccessful cardiopulmonary resuscitation of cardiac arrest in the ICU. An outline of organ-specific requisites for kidney, liver, heart, and lung transplantation following DCDD and techniques, such as normothermic regional perfusion (nRP) and ex vivo machine perfusion, has been provided. The outcomes of transplantation following DCDD are comparable to those following DBDD or living donor transplantation. Documents and checklists necessary for successful execution of DCDD in India are described. How to cite this article: Seth AK, Mohanka R, Navin S, Gokhale AGK, Sharma A, Kumar A, et al. Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper. Indian J Crit Care Med 2022;26(4):421-438.

COVID-19 Pandemic Research Opportunities in India: What the Pandemic Is Teaching Us About Transplantation.

Coronavirus disease (COVID-19) has engulfed the whole world, and India has been the second worst-hit nation. Organ transplant services were halted in both the public and private care sectors of India, with public care sectors more adversely affected. Deceased donations were disproportionately more affected, with unfavorable rates at the peak of the pandemic. Mortality outcomes of COVID-19 among different organ transplant recipients in India have been lower compared with the Western world, with younger age and less comorbidities among Indian populations partly responsible for the lower mortality. Mortality and graft loss were mostly associated with older age and those with chronic graft dysfunction. During the pandemic, invasive fungal infections, like mucormycosis, have been reported, illustrating the need for multidisciplinary management. The Indian transplant societies have formulated and timely revised guidelines for transplantation in the COVID-19 era. Living donor transplants (both liver and kidney) after recovery from COVID-19 were both first described in India, providing a guiding tool for the world. Follow-up reports of recovered solid-organ transplant recipients have also been reported in Indian studies, showing reassuring long-term outcomes. Data of breakthrough COVID-19 cases after vaccination among both transplant recipients and waitlist candidates and research in vaccine efficacy for solid-organ transplant recipients is still underway. We suggest continuing and intensifying research activities for a better plan and strategy in case of a future pandemic.

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.