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.

Renal Transplantation in Patients With Tuberculosis: A Single-center Experience From an Endemic Region.

Background: Despite being a common infection in end-stage kidney disease patients, there are no evidence-based guidelines to suggest the ideal time of transplantation in patients on antitubercular therapy (ATT). This study aimed to examine the outcome of transplantation in patients while on ATT compared with those without tuberculosis (TB). Methods: This was a retrospective study. Renal transplant recipients transplanted while on ATT were compared with a 1:1 matched group (for age, sex, diabetic status, and type of induction agent) of patients without TB at the time of transplant. Patient outcomes included relapse of TB and graft and patient survival. Results: There were 71 patients in each group. The mean duration for which ATT was given pretransplant was 3.8 ± 2.47 mo. The average total duration of ATT received was 12.27 ± 1.25 mo. Mortality in both the groups was similar (8.4% in the TB group versus 4.5% in the non-TB group; P = 0.49). None of the surviving patients had recurrence of TB during the follow-up. Death-censored graft survival (98.5% in the TB group versus 97% in the non-TB group; P = 1) and biopsy-proven acute rejection rates (9.86% in the TB group versus 8.45% in the non-TB group; P = 1) were also similar in both the groups. Conclusions: Successful transplantation in patients with end-stage kidney disease on ATT is possible without any deleterious effect on patient and graft survival and no risk of disease recurrence. Multicentric prospective studies are needed.

COVID-19 in Renal Transplant Recipients - A Single Center Experience from India.

Introduction: The information on the clinical outcome of renal transplant recipients getting COVID-19 infection is sparse. The aim of this study is to report a single-center experience of renal transplant recipients with COVID-19 from India. Methods: This was a retrospective study of 23 consecutive renal transplant recipients with COVID-19 infection presenting to our center from May 2020 to August 2020. Clinical parameters, laboratory values, imaging characteristics, and outcome of the patients were collected and analyzed. Results: Median follow-up duration was 36 (range: 10-110) days. Median age of patients was 54 (23-70) years, and 87% were male. Median duration since transplant was 69 (range: 15-132) months. The most common presenting feature was fever (82.6%), followed by breathlessness (43.5%) and cough (30.4%). Hospitalization rate was 52.2%, while 34.8% required ICU care. Severe to critical disease was seen in 39.1% of patients, and 17.4% required mechanical ventilation. Patients with severe disease had a higher incidence of lymphopenia (P = 0.005) when compared to the ones with mild to moderate disease. Acute kidney injury was seen in 39.1% of patients, and 13% required dialysis. Mortality rate was 13% overall, and 25% in those hospitalized. Conclusion: Renal transplant recipients with COVID-19 have a poor outcome. Although not all of them need hospitalization, they should be monitored closely. Immunosuppression minimization is an important part of the treatment strategy.

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.

ABO-Incompatible Kidney Transplantation in India: A Single-Center Experience of First Hundred Cases.

Aim: ABO-incompatible (ABOi) kidney transplantation overcomes immunological barrier of blood group incompatibility. There have been very few published experiences of ABOi kidney transplantation from India. We present our single-center experience of the first hundred ABOi kidney transplants. Material and Methods: This is a single-center retrospective study of consecutive first hundred ABOi kidney transplant with at least 6 months of follow-up. Results: During the study period (2011-2020), a total of 121 ABOi kidney transplants were performed. Of these, first hundred patients were analyzed. Median follow-up duration was 33 (10-101) months. Mean recipient and donor age were 41.5 ± 13 and 47.68 ± 11.25 years, respectively. Mean HLA mismatch was 4 ± 1.5. Median baseline anti-blood group antibody titer was 128 (2-1024). Most common recipient blood group was O. Patient and death censored graft survival was 93% and 94%, respectively, at median follow-up of 33 months. Biopsy-proven acute rejection (BPAR) rate was 17% with acute antibody-mediated rejection being 3%. Rate of infection was 37%, most common being urinary tract infection. Conclusion: ABOi kidney transplant patients had acceptable patient and graft survival as well as BPAR rates. With current preconditioning protocol, infection rate was high.

Treatment and Outcomes of Coronavirus Disease 2019 in Kidney Transplant Recipients: A Single-center Experience.

There is a paucity of literature about the outcomes of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 after kidney transplantation in developing countries (e.g., India). We included 50 consecutive kidney transplant recipients diagnosed with COVID-19 from August 2020 to December 2020. The mean age was 50 ± 10 years, and the median interval since transplantation was 34 months. Fever (100%), cough (40%), and shortness of breath (32%) were the most common presenting symptoms. Mild disease occurred in 26 patients, moderate disease in 12, and severe disease in 12. All 24 patients with moderate-to-severe disease received remdesivir and high-dose steroids, whereas 17 of 26 patients with mild disease received favipiravir. Convalescent plasma was given to 13 of 24 patients with moderate-to-severe disease, and 7 of 12 patients with severe disease received tocilizumab. The median hospital stay was 7 days (interquartile range: 4-20 days). Of 30 patients who developed acute kidney injury, seven required renal replacement therapy and eight required mechanical ventilation. Eight patients with severe disease died. An age of >50 years, coughing, shortness of breath at presentation, C-reactive protein levels of >100 mg/dL, D-dimer levels of >1 mg/L, computed tomography severity scores of >20 at presentation, supplemental oxygen, and mechanical ventilation correlated significantly with mortality in our cohort. COVID-19 infection in kidney transplant recipients had a high mortality rate; however, remdesivir and high-dose steroids were associated with better outcomes compared with earlier studies.

Grafalon® vs. Thymoglobulin® as an Induction Agent in Renal Transplantation - A Retrospective Study.

INTRODUCTION: Antihuman thymocyte immunoglobulin, used as an induction agent in renal transplantation, is of two types - thymoglobulin and grafalon (formerly ATG-Fresenius). In this study, we compared outcomes with these two agents. METHODS: This was a single-center retrospective study of patients transplanted from January 2017 to October 2019, who received either grafalon or thymoglobulin induction. Grafalon or thymoglobulin was given at 6 and 3 mg/kg, respectively, followed by standard triple immunosuppression of tacrolimus, MMF, and prednisolone. RESULTS: Median follow up was 22 (3-36) months. Thymoglobulin was given to 255 patients, whereas 78 patients received grafalon. Baseline demographics were similar between the two groups although significantly more patients in the grafalon group received ABO incompatible transplant (15% vs. 4.3%; P = 0.002). Patient survival was similar between the two groups (99% in grafalon vs. 98.8% in thymoglobulin; P = 1.0). Death censored graft survival was also similar (99% in grafalon vs. 100% in thymoglobulin; P = 0.23). Biopsy proven acute rejection (BPAR) was significantly higher in the grafalon group (12.8% vs. 5.1%, P = 0.04). The significance persisted after multivariable regression analysis (P = 0.02). Other outcomes such as infection rate and estimated glomerular filtration rate on last follow up were comparable between the two groups. CONCLUSIONS: Grafalon (6 mg/kg dose) when used as an induction agent was associated with significantly higher rate of BPARs as compared to thymoglobulin (3 mg/kg dose) although with comparable short-term patient and death censored graft survival, graft function, and infection rates.

A retrospective multi-center experience of renal transplants from India during COVID-19 pandemic.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic led to a sudden drop in renal transplant numbers across India in the initial months of 2020. Although the transplant numbers increased with easing of lockdown, the outcome of these transplants remains unknown. METHODS: This was a retrospective, observational, multi-center study done across eight different transplant centers in India. All the transplants done from January 30, 2020 to December 31, 2020 were included. The primary outcomes studied were patient and death censored graft survival as well as incidence of COVID-19 infection and its outcomes. RESULTS: During the study period a total of 297 kidney transplants were done. After a median follow up of 265 days the patient and death censored graft survival was 95.3% and 97.6%, respectively. Forty-one patients (13.8%) developed COVID-19 post-transplant. Majority (58.5%) were asymptomatic to mildly symptomatic and the case fatality ratio was 14.6%. On multivariable logistic regression analysis older age was associated with higher likelihood of COVID-19 infection (odds ratio 1.038; CI 1.002-1.077). CONCLUSIONS: Patient and graft outcome of kidney transplants done during the COVID-19 pandemic in India was acceptable. The incidence of COVID-19 was 13.8% with a high case fatality ratio.

Haemodialysis vascular access: current practices amongst Indian nephrologists.

INTRODUCTION: Despite the growing number of haemodialysis (HD) patients in India, little is known about vascular access practice. We investigated the use and cost of different vascular accesses by Indian nephrologists. METHODS: An online survey was emailed to 920 Indian nephrologists and 388 (42.1%) responded; 98.5% of whom were responsible for managing dialysis patients, 98% in hospitals. RESULTS: Sixty-four percent of patients initiated renal replacement therapy with HD, 7% with peritoneal dialysis, 10% kidney transplantation and 19% conservative care. Forty-eight percent of patients were self-paying, 26% had employee reimbursement and 23% had insurance. According to 59% of responders, more than three-quarters of patients started dialysis with uncuffed catheter, less than one-quarter started dialysis with fistula; and very few used grafts or tunnelled catheters. Among prevalent HD patients, over half were dialysing with fistula (79% nephrologists), rather than uncuffed catheters (15% nephrologists) or grafts (<1% nephrologists). Sixteen percent reported at least one catheter-related sepsis in more than half of patients. Placement of uncuffed catheters cost US$160 in 92% facilities, whereas tunnelled catheters cost US$320 in 46% of facilities. An arteriovenous fistula (AVF) could be created for US$160 in 40%, and US$320 in 90% of centres. Thirty-five percent of nephrologists reported that grafts were not placed at their institute and where they were available, the average cost was over US$480. Forty-six percent of nephrologists had access to pre-dialysis clinics, <30% to vascular access programmes, and <17% conducted regular vascular access audits. CONCLUSIONS: The survey provides a snapshot of the current status of vascular access care in HD patients and highlights need for pre-dialysis clinics, vascular access services and registry audits.

Deferred pre-emptive switch from calcineurin inhibitor to sirolimus leads to improvement in GFR and expansion of T regulatory cell population: a randomized, controlled trial.

BACKGROUND: Measures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (T(reg)) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and T(reg) frequency. METHODS: In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. T(reg) population was estimated by flowcytometry. RESULTS: Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94 ± 11.78 vs 80.59 ± 16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in T(reg) population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event. CONCLUSIONS: A deferred pre-emptive switch over from CNI to SIR safely improves renal function and T(reg) population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034).

Antiwear performance and mechanism of an oil-miscible ionic liquid as a lubricant additive.

An ionic liquid (IL) trihexyltetradecylphosphonium bis(2-ethylhexyl) phosphate has been investigated as a potential antiwear lubricant additive. Unlike most other ILs that have very low solubility in nonpolar fluids, this IL is fully miscible with various hydrocarbon oils. In addition, it is thermally stable up to 347 °C, showed no corrosive attack to cast iron in an ambient environment, and has excellent wettability on solid surfaces (e.g., contact angle on cast iron <8°). Most importantly, this phosphonium-based IL has demonstrated effective antiscuffing and antiwear characteristics when blended with lubricating oils. For example, a 5 wt % addition into a synthetic base oil eliminated the scuffing failure experienced in neat oil and, as a result, reduced the friction coefficient by 60% and the wear rate by 3 orders of magnitude. A synergistic effect on wear protection was observed with the current antiwear additive when added into a fully formulated engine oil. Nanostructure examination and composition analysis revealed a tribo-boundary film and subsurface plastic deformation zone for the metallic surface lubricated by the IL-containing lubricants. This protective boundary film is believed to be responsible for the IL's antiscuffing and antiwear functionality.