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.

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.

Clinical Profile and Outcome in Long-term Hemodialysis: A Comparative Study of Hospital-based Versus Standalone Units.

Introduction: Chronic hemodialysis (CHD) remains the most "resorted to" renal-replacement option in India. Pursuit for accessible and affordable dialysis has resulted in setting up standalone centers (SACs). We need more Indian data on the profile of CHD population and outcome of SAC compared to hospital-based units (HBUs). Material and Methods: We analyzed the clinical profile of patients on CHD for >5 years, compared the outcome between HBU and SAC, and analyzed the factors associated with mortality. Patients initiated between January 1, 2006 and December 31, 2012 and who have survived 5 years on CHD at HBU or SAC were enrolled and followed up prospectively for 2 years. Their clinical and biochemical profile, comorbidities, long-term complications, and mortality were analyzed. Results: The study included 137 patients, 41 (30%) from HBU and 96 (70%) from SACs. In both groups, the patients were predominantly male, aged 51-70 yrs, diabetic, unplanned initiation through catheters, and had average-dialysis vintage between 83 and 85 months. SAC had more patients with hemoglobin (> 11 gm/dL) and hyperparathyroidism with elevated SAP levels (P < 0.05). Both groups had comparable iron stores, serum calcium, and phosphorus. Comparable between groups, infections, coronary artery disease, and access complications accounted for most hospitalizations and sudden cardiac death and sepsis accounted for most mortality. A trend of better survival was seen in SAC. Multivariate analysis showed anemia, DM and hospitalizations were associated with mortality. Conclusion: We conclude that the outcomes of long-term CHD at SACs are not inferior to HBUs. Anemia, diabetes, and hospitalizations were associated with overall mortality. Benefits of SACs in cost, QOL, and employment opportunities need to be studied in the Indian context.

Hemodialysis-related Portal-systemic Encephalopathy: A Rare Cause of Recurrent Encephalopathy among Patients on Maintenance Hemodialysis.

Portal-systemic venous shunts can rarely develop without any intrinsic liver diseases. However, the cause of shunt formation in these cases are not very clear. Literature suggests that hemodialysis can precipitate symptoms in patients with asymptomatic portal-systemic venous shunts (PSVS). Rare presentations of recurrent encephalopathy due to PSVS in the absence of liver dysfunction has been described in patients undergoing hemodialysis. We report a rare case of recurrent Hemodialysis Related Porto-Systemic Encephalopathy (HRPSE) in a 50-year old male during maintenance hemodialysis secondary to a PSVS between the portal vein and left renal vein. Shunt embolism by an 18 mm Amplatzer vascular plug (AVR II) was done and follow up CT showed complete occlusion of collaterals. Post-procedure, he is undergoing thrice-weekly Hemodialysis of 4 hours duration till date with no further incidence of encephalopathy. Our report indicates that recurrent encephalopathy can occur in dialysis patients due to symptomatic PSVS and HRPSE should be considered even in non-cirrhotic cases for early detection and effective management.

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.

Outcomes of Spousal versus Parental Donor Kidney Transplants: A Comparative Study.

INTRODUCTION: Parents and spouse constitute 70% of organ donors in India. Some centres use induction immunosuppression (IS) for all spousal transplants considering it as an immunologically high risk. This study was designed to compare the outcomes of transplant recipients who received parental donors (PDs) and spousal donors (SDs) without any induction IS. METHODS: It was a retrospective study conducted at a tertiary care hospital in South India. Adults aged 18 years or above who underwent renal transplantation from a SD or PD between January 2006 and December 2016 were included in the study. RESULTS: Our study included 154 patients with PDs and 75 patients with SDs. The mean recipient age of the PD group was 27.79 ± 6.85 years and of the SD group was 45.62 ± 7.96 years (P < 0.001). However, the follow-up period was significantly higher for the PD group (P < 0.05). There was no significant difference between acute rejection, patient loss, mean survival, graft survival (uncensored), and death censored graft survival between two groups. CONCLUSION: The outcomes of immunologically low-risk transplant recipients who have received PD and SD are similar and induction immunosuppression can be avoided in these patients.

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.

The Prevalence of Frailty and its Association with Cognitive Dysfunction among Elderly Patients on Maintenance Hemodialysis: A Cross-Sectional Study from South India.

Data are scarce regarding the prevalence of frailty in elderly patients undergoing maintenance hemodialysis (HD) in India. We conducted a cross-sectional observational study aimed to study the prevalence of frailty and cognitive dysfunction in patients aged 75 years or more undergoing maintenance HD in three tertiary care hospitals and associated stand-alone dialysis centers in North Kerala. Frailty was ascertained by two methods. In method 1 (physical performance measurement based), dichotomous scoring (0 or 1) of five domains, namely weight loss, exhaustion, low physical activity, weak grip, and slow walking, was done, and a score of 3/5 was used to define frailty. In method 2 (self-report measure based), scores on the Medical Outcomes Study Short-Form 36-item Questionnaire (SF-36) physical function domain were used instead of hand grip strength and walking speed, and a score of <75 was defined as meeting the criteria for weakness and slow walking. Cognitive function was documented using the Montreal Cognitive Assessment Instrument. A total of 899 patients were screened, of whom 44 were aged 75 years or more and 39 met the criteria for inclusion. The majority (n = 31, 79.5%) had ages between 75 and 80 years and were male. Dialysis vintage was <1 year in 15.4%, 1-3 years in 51.3%, and >3 years in 33.3% of patients. Frailty was documented in 22 (56.4%) patients by method 1 and in 25 (64.1%) by method 2. There was a statistically significant difference between the two methods in documenting frailty (P < 0.001, Chi-square test). Cognitive impairment was present in 89.7% of patients and significantly associated with frailty (P < 0.001, Fisher's exact test). Frailty and cognitive dysfunction are highly prevalent in elderly people undergoing maintenance HD in North Kerala. Physical performance and self-report measure-based methods correlate well in frailty documentation.

ABO-incompatible transplantation without conventional induction immunosuppression (IL-2RB or depleting agents).

Transplantation across the ABO blood group (ABOI-Tx) has facilitated to increase in donor pool for living donor kidney transplantation. Increased risk of rejection despite augmented immunosuppression has been the concern for many transplant programs in initiating an ABOI-TX program. The benefits of induction immunosuppression on long-term graft survival in immunologically low-risk individuals are still not clear. Increased immunosuppression of ABOI-Tx recipients before transplantation could provide an opportunity to transplant without induction with IL2-R blockers or Lymphocyte depleting agents. The aim of our study is to analyze the outcome of our series of 25 consecutive ABOI-Tx patients who underwent transplantation without routine thymoglobulin or IL2R-blocker induction. Our study is a prospective observational study for the first 25 consecutive patients who had undergone ABOI-Tx from two tertiary care centers in Kerala, India, having the same IS protocol. Anti-A and anti-B titers ≤1:512 by Gel-method (Biorad) were accepted for desensitization. Patients underwent CDC-crossmatch, Flow-crossmatch, and Luminex-anti-HLA-antibody-screen. Desensitization regimen included- Rituximab 200 mg on Day-21, Triple IS Prednisolone 10 mg, mycophenolate mofetil 1000 mg, and Tacrolimus 0.06 mg/bodywt from Day-14 and Plasma-exchange (PLEX) 3-4 sessions from day -7 to attain titer of 1:8 before transplantation. Transplantation was done without induction IS. Twenty-five patients underwent ABOI-Tx from both centers. Twenty recipients were male. The average age was 34.5 ± 8 years with follow-up of 503 ± 120 days. Eight donors were spouse, 13 were parents and three siblings. The average age of the donor was 46.3 ± 10.5 years. Twenty-two patients have normal functioning transplant with creatinine 1.23 ± 0.2 mg/dL. Kaplan-Meier analysis showed patient survival of 91.2% and death censored graft survival of 95.6% at 36 months. Two patients were lost; one on the postoperative day (POD)-3 due to ACS and second on POD-22 due to sepsis. One graft loss occurred due to posttransplant HUS. Of the functioning 22 allograft-recipients, one had cellular rejection, which resolved with pulse steroids; one developed HUS due to CNI, which recovered with PLEX and switch to non-CNI based IS. One patient developed AMR on POD-4, which was completely reversed with PLEX, intravenous immunoglobulin (IVIG), and augmentation of IS. Three patients had CMV viremia and another three patients had BKV viremia, all resolved with treatment and tailoring of IS. Achieving acceptable anti-A/B titers prior to transplantation is the most critical step in ABOI-Tx. Avoidance of induction IS can reduce cost and infectious complications. Our data showed that there is no increased incidence of rejections in the first post-transplant year for immunologically low-risk individuals from histocompatibility standpoint undergoing ABOI-Tx without induction immunosuppression.

The expanding role of "Stand-Alone" hemodialysis units in chronic renal replacement therapy: A descriptive study from North Kerala.

Renal replacement therapy in India is predominantly a private health-care-driven initiative making it an expensive treatment option due to high out-of-pocket expenditures. Moreover, with the rapid increase in the number of chronic kidney disease patients requiring dialysis, hemodialysis units (HDUs) are getting saturated. Community "stand-alone" dialysis centers could be an important alternative to HDUs in meeting the growing demand in an affordable model. The aim of this study was to find hemodialysis (HD) delivery in "stand-alone" dialysis units (SAUs) with respect to expanding coverage, patient costs, and patient safety safeguards. The total number of HD sessions was collected at three points. The information regarding patient safety safeguards at SAUs and impact of SAUs on patient costs were collected by interviews and from hospital records. There was 11.5 times increase in HD sessions from 2008 to 2017, out of which 75.3% was provided at SAUs. Following objective clinical and safety measures, high-quality dialysis was delivered at SAUs and it significantly reduced the mean patient cost of treatment per session.

Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clinical implications.

BACKGROUND: Chronic Renal Allograft Dysfunction (CRAD) is responsible for a large number of graft failures. We have abrogated acute T-cell rejections using Ahmedabad Tolerance Induction Protocol (ATIP) with hematopoietic stem cell transplantation (HSCT) under non-myeloablative conditioning pre-transplant. However B-cell mediated rejections and CRAD continue to haunt us. We carried out retrospective analysis of renal allograft biopsies performed in the last 4 years to evaluate the effect of ATIP on CRAD. MATERIALS AND METHODS: Biopsies diagnosed as per modified Banff criteria belonged to 2 groups: ATIP under low dose immunosuppression of cyclosporine/Azathioprine/Mycofenolate mofetil+ Prednisolone, subjected to donor leucocyte transfusion, anti-T/B cell antibodies, low dose target specific irradiation, cyclophosphamide, cyclosporin followed by HSCT pre-transplant; controls who opted out of ATIP were transplanted under standard triple drug immunosuppression. Demographics of both groups were comparable. RESULTS: Incidence of chronic changes was higher in controls (17.5%) vs. 10.98% in ATIP over a mean follow up of 151.9 months in the former and 130.9 months in the latter. Proteinuria and hypertension were higher in controls (48.4%) vs. ATIP (32.7%) with chronic transplant glomerulopathy, focal global sclerosis in 67.7% in controls vs. 46.7% in ATIP, acute on chronic T/B cell rejection in 51.6% controls vs. 28.1% ATIP, with peritubular capillary C4d deposits in 19.4% controls vs. 1.9% ATIP biopsies. Acute on chronic calcineurin inhibitor toxicity was higher in ATIP (71.9%) vs. 48.4% in controls. CONCLUSION: Chronic immune injury was less with ATIP vs controls as compared to a higher incidence of chronic calcineurin inhibitor toxicity in the former.

Nephrotic presentation in hydatid cyst disease with predominant tubulointerstital disease.

Renal involvement, which can rarely occur in echinococcosis, more commonly manifests as hydatid cyst of the kidney. Scattered case reports of nephrotic syndrome secondary to hydatid cyst in the liver or lung have been reported for over two decades. The glomerular picture varied from minimal change lesion to mesangiocapillary glomerulonephritis. We report a case of predominantly tubulointerstitial nephritis with mesangioproliferative glomerulonephritis in a patient with hepatic hydatid cyst which responded to cyst resection alone.