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.

A Multicenter Cohort Study From India of ABO-Incompatible Kidney Transplantation in Post-COVID-19 Patients.

BACKGROUND: There is a dearth of data regarding the consequences of ABO-incompatible kidney transplant (ABOiKTx) among post-COVID-19 candidates. METHODS: The study was designed as a retrospective, multicentric cohort study across 11 sites in India, from August 2020 to December 2021. The data for ABOiKTx conducted for post-COVID-19 candidates were investigated. The primary outcome of biopsy-proven acute rejection was compared with the ABO protocol implemented through Kaplan-Meier analysis. The secondary outcomes were graft loss, patient survival, and infections. RESULTS: A total of 38 ABOiKTx with candidates of median (interquartile range) age of 38.5 (31.25-47.5) years were performed. Nineteen cases had mild COVID-19 severity, while 9 cases (23.6%) had an oxygen requirement. Six (15.7%) donors also were post-COVID-19. The most common ABO incompatibility reported was A to O in 14 (36.8%) pairs followed by B to O in 10 (26.3%) pairs. The maximum isoagglutinin titer cutoff was 1:2048 and 1:64 for baseline and pretransplant levels, respectively. The median time from COVID-19 infection to surgery was 130 (63.2-183) days. Biopsy-proven acute rejection, graft loss, and mortality were 13.1%, 2.6%, and 2.6%, respectively. The Breslow-Wilcoxon's P value in Kaplan-Meier plots were 0.57 and 0.93 for thymoglobulin-based induction and high dose rituximab-based regimen, respectively. The incidence of reinfection was 2.6%. Two (5.2%) urinary tract infections were reported. No cytomegalovirus or BK polyomavirus infection was reported. The median serum creatinine at 1 year of follow-up was 1.1 (0.8-1.3) mg/dL. CONCLUSIONS: Our report implies that ABOiKTx in post-COVID-19 candidates can be successfully performed with no major deviation from standard ABO protocol.

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.

A Multicenter Cohort Study From India of 75 Kidney Transplants in Recipients Recovered After COVID-19.

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.

Adult-onset nephrotic syndrome following coronavirus disease vaccination.

A 22-year-old healthy man was admitted for oedema 15 days after the first injection of the COVISHIELD coronavirus disease 2019 (COVID-19) vaccine (Oxford AstraZeneca) vaccine. Nephrotic syndrome was diagnosed and a kidney biopsy showed minimal change disease. Oral prednisolone was started at 1 mg/kg/day resulting in complete remission within 1 week.

Impact of COVID-19-associated Mucormycosis in Kidney Transplant Recipients: A Multicenter Cohort Study.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is a recently emerging entity. There is a lack of reports of CAM in organ transplant recipients. METHODS: We conducted a multicenter (n = 18) retrospective research in India during November 2020 to July 2021. The purpose of this study was to explore the clinical spectrum, outcome and risk factors for mortality of CAM in kidney transplant recipients (KTRs). RESULTS: The incidence of CAM was 4.4% (61/1382 COVID-19-positive KTRs) with 26.2% mortality. The median age of the cohort was 45 (38-54) y. Twenty (32%) were not hospitalized and 14 (22.9%) were on room air during COVID-19. The proportion of postdischarge CAM was 59.1%, while concurrent CAM was reported in 40.9%. The presentation of CAM was 91.8% rhino-orbital-cerebral mucormycosis and 8.2% pulmonary with 19.6% and 100% mortality, respectively. In the univariable analysis, older age, obesity, difficulty of breathing, high-flow oxygen requirement, and delay in starting therapy were significantly associated with mortality. In the multivariable logistic regression analysis, patients requiring high-flow oxygen therapy [odds ratio (95% confidence interval) = 9.3 (1.6-51); P = 0.01] and obesity [odds ratio (95% confidence interval) = 5.2 (1-28); P = 0.05] was associated with mortality. The median follow-up of the study was 60 (35-60) d. CONCLUSIONS: We describe the largest case series of CAM in KTRs. Morality in pulmonary CAM is extremely high. Severe COVID-19 pose extra risk for the development of CAM and associated mortality. Our report will help in better understanding the conundrum and management of CAM.

Effect of Coronavirus Disease 2019 on Transplantation and Nephrology in India: A Nationwide Report From India.

BACKGROUND: The 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. METHODS: We 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. RESULTS: On 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%). CONCLUSIONS: COVID-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.

Is Early COVID-19 in Kidney Transplant Recipients Concerning Enough to Halt Transplantation? A Multicenter Comparative Analysis from India.

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 COVID-19 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). COVID-19 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.

A Multicenter Cohort Study of Indian Centers on Reoccurring SARS-CoV-2 Infections in Kidney Transplant Recipients.

OBJECTIVES: There is scarcity of data on reoccurrence of SARS-CoV-2 infections in kidney transplant recipients. MATERIALS AND METHODS: We conducted a retrospective multicenter cohort study and identified 13 kidney transplant recipients (10 living and 3 deceased donors) with recurrent COVID-19, and here we report demographics, immunosuppression regimens, clinical profiles, treatments, and outcomes. RESULTS: COVID-19 second infection rate was 0.9% (13/1350) in kidney transplant recipients with a median age of 46 years; median time interval from transplant to first episode of COVID-19 diagnosis was 9.2 months (interquartile range, 2.2-46.5 months). The most common comorbidities were hypertension (84%) and diabetes (23%). Fever was significantly less common with recurrent COVID-19. COVID-19 severity ranged from asymptomatic (23%), mild (31%), and moderate (46%) during the first infection and asymptomatic (8%), mild (46%), and severe (46%) in the second infection. All 6 kidney transplant recipients with severe second infections died. The median interval between the 2 episodes based upon reverse transcriptase polymerase chain reaction COVID-19-positive tests was 135 days (interquartile range, 71-274 days) without symptoms. Statistically significant risk factors for mortality were dyspnea (P = .04), disease severity (P = .004), allograft dysfunction (P < .05), higher levels of neutrophil-to-lymphocyte ratio (P = .05), and intensive care unit/ventilator requirement (P = .004). Although our limited resources did not allow for molecular diagnostics and typing, we suggest that these second episodes were reinfections with SARS-CoV-2. CONCLUSIONS: To our knowledge, this is the largest study of kidney transplant recipients with reoccurring SARS-CoV-2 infection, and we observed 46% mortality.

Is it Safe to Be Transplanted From Living Donors Who Recovered From COVID-19? Experience of 31 Kidney Transplants in a Multicenter Cohort Study From India.

BACKGROUND: There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19. METHODS: Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery. RESULTS: COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19. CONCLUSIONS: Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.

Clinical Profile and Outcome of COVID-19 in 250 Kidney Transplant Recipients: A Multicenter Cohort Study From India.

BACKGROUND: There is a scarcity of data on the consequences of coronavirus disease-19 (COVID-19) infections in kidney transplant recipients (KTRs) from emerging countries. METHODS: Here, we present a cohort study of 13 transplant centers in India including 250 KTR (226 living and 24 deceased donors) with polymerase chain reaction-confirmed COVID-19 positivity from March 23, 2020, until September 15, 2020. We detailed demographics, immunosuppression regimen, clinical profile, treatment, and outcomes. RESULTS: Median age of transplant recipients was 43 years, and recipients presented at a median of 3.5 years after transplant. Most common comorbidities (94%) included arterial hypertension (84%) and diabetes (32%); presenting symptoms at the time of COVID-19 included fever (88%), cough (72%), and sputum production (52%). Clinical severity ranged from asymptomatic (6%), mild (60%), and moderate (20%) to severe (14%). Strategies to modify immunosuppressants included discontinuation of antimetabolites without changes in calcineurin inhibitors and steroids (60%). Risk factors for mortality included older age; dyspnea; severe disease; obesity; allograft dysfunction before COVID-19 infection; acute kidney injury; higher levels of inflammatory markers including C-reactive protein, interleukin-6 level, and procalcitonin; chest X-ray abnormality, and intensive care unit/ventilator requirements. Overall patient mortality was 11.6% (29 of 250), 14.5% (29 of 200) in hospitalized patients, 47% (25 of 53) in intensive care unit patients, and 96.7% (29 of 30) in patients requiring ventilation. KTRs with mild COVID-19 symptoms (n = 50) were managed as outpatients to optimize the utilization of scarce resources during the COVID-19 pandemic. CONCLUSIONS: Mortality rates in COVID-19-positive KTR appear to be higher than those in nonimmunosuppressed patients, and high mortality was noted among those requiring intensive care and those on ventilator.