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.

Comparison of Thymoglobulin and Grafalon as Induction Agents in Renal Transplantation: A Prospective Study.

BACKGROUND: Induction immunosuppression is used to reduce the incidence of acute rejection and prevent delayed graft function. The 2 rabbit anti-thymocyte globulins- thymoglobulin and Grafalon (ATG Fresenius) have been commonly used for induction immunosuppression and treatment of acute rejection in solid organ transplantation. There are very few studies comparing the efficacy and side effects of both the anti-thymocyte globulins therefore this prospective study comparing the 2 types of anti-thymocyte globulins would be of clinical interest. PATIENTS AND METHODS: This prospective single center study was conducted at Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, India from April 2019 to June 2020. Sixty-two ABO-compatible renal transplant recipients were included in the study. They were divided in 2 groups of 31 patients each. One group received thymoglobulin (3 mg/kg) and the second group received Grafalon (6 mg/kg). All patients were followed up for 12 months and the 2 groups were compared for incidence of rejections, infections, graft function, patient survival, and graft survival. RESULTS: There was no significant difference in the incidence of rejections, infective episodes, graft function, posttransplant diabetes mellitus, graft survival and patient survival in thymoglobulin or Grafalon groups. The hematological parameters were similar in both groups at 7 days, 1 month, and 6 months of follow-up. The absolute lymphocyte count was significantly lower in the thymoglobulin group at 12 months posttransplant. CONCLUSIONS: Thymoglobulin and Grafalon were found to be equivalent in terms of safety and efficacy in short term, with no difference in rejections, infections, graft survival, or patient survival.

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.

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.

Effect of Different Rituximab Doses on B Cell Count, Anti-A/B Antibody Titer, Graft Function, and Infectious Complications in ABO-Incompatible Renal Transplantation: A Prospective Study.

BACKGROUND: ABO-incompatible kidney transplantation (ABOiKT) has been accepted as a viable and cost-effective modality with outcomes comparable to ABO-compatible transplants, but there is a concern regarding higher infectious complications in ABOiKT because of the heightened immunosuppression. The desensitization protocol normally includes antibody removal, B cell depletion by rituximab (RTX), and immunomodulation with intravenous immunoglobulin. Efforts have been made over the years to decrease the dose of RTX in an effort to decrease the infective complications. There is limited literature about the minimum effective dose of RTX, which can cause an effective B cell depletion. This prospective study was designed to correlate the RTX dose with peripheral absolute B cell count, graft function, graft and patient survival, and infective complications. METHODS: This study included 52 adult ABOiKT recipients with anti-A/B antibody titer up to a maximum of 1:512. The participants were divided into 2 groups of 26 each according to the RTX dosage used: Group A received 100 mg/patient, and Group B received 200 mg/patient. RTX was given 14 days prior to transplant after B cell measurement by flow cytometry. The outcomes were compared after 1 year of follow-up. RESULTS: Both the dosages effectively depleted the absolute B cell count. Although patient survivals, graft survival, graft function, acute rejection episodes, and post-transplant hospital stay were similar in both groups, infective complications were significantly higher in group B. CONCLUSION: A low dose (100 mg/patient) of RTX produces effective depletion of B cells while lowering the infective complications in ABOiKT.

An Unusual Case of a Dematiaceous Fungus with an Exclusive Cerebral Involvement After ABO-Incompatible Renal Transplantation.

BACKGROUND Cladophialophora carrionii was detected postoperatively in a cerebral space-occupying lesion of a patient who had undergone ABO-incompatible renal transplantation. The infection was successfully treated with oral terbinafine and itraconazole. CASE REPORT An otherwise healthy 46-year-old man underwent ABO-incompatible renal transplantation. Postoperatively, he was hemodynamically stable and the graft was functioning well. Within 2 weeks, the patient developed clinical depression, followed by seizures and left-side hemiparesis. There were no skin findings. Radiological investigation showed 2 space-occupying lesions in the brain parenchyma. The patient's condition improved after partial frontal lobectomy and microsurgical abscess evacuation, with a short course of liposomal amphotericin B and a combination of oral terbinafine and itraconazole. Microbiological examination of the pus showed growth of C. carrionii, which predominantly causes subcutaneous mycoses. CONCLUSIONS It is very rare for melanized fungal infections to cause an exclusively cerebral disease without any skin involvement. Furthermore, among established cases, C. carrionii is a very rarely detected pathogen.

Successful Third Kidney Transplant After Desensitization for Combined Human Leucocyte Antigen (HLA) and ABO Incompatibility: A Case Report and Review of Literature.

BACKGROUND In the present era, kidney transplantation across immunological barriers (ABO incompatibility and human leucocyte antigen (HLA) incompatibility) is a successful strategy to provide transplantation to immunologically high-risk patients. The safety and outcome of crossing both ABO and HLA barriers simultaneously in a retransplantation scenario is rarely reported from the developing world. CASE REPORT A 30-year-old female underwent a third living donor kidney transplantation. Her previous 2 transplants being lost to chronic allograft nephropathy. The transplantation was done across a simultaneous blood group as well as HLA incompatibility. The donor was the mother who was blood group B, with the recipient being blood group O. The complement dependent cytotoxicity crossmatch of the pair was negative but the flow cross match for T as well as B lymphocytes was positive. The mean fluorescence intensity value for class I antigens was 6951 and that for class 2 antigens was 7534. The patient underwent a desensitization procedure including rituximab, plasmapheresis and intravenous immunoglobulin pre-transplantation. The pre-transplantation isohemaglutunin titer was <1: 8 and the donor specific antibody against class 1 antigens was <2200 and <770 against class 2 antigens. Induction was done with anti-thymocyte globulin in the dose of 3 mg/kg in 2 divided doses. The patient is maintained on triple immunosuppression with tacrolimus, prednisolone and mycophenolate mofetil. After a follow-up period of 5 months, she maintains a good graft function with serum creatinine of 1.01 mg/dL. CONCLUSIONS With the advances in the desensitizing procedures in the developing world, kidney transplantation across a combined HLA and ABO incompatible barrier can be offered to these highly sensitized patients, even in case of retransplantation.

Comparative analysis of ABO-incompatible kidney transplantation with ABO-compatible transplantation: A single-center experience from Eastern India.

This study aimed to compare the outcomes of ABO-incompatible kidney transplantation (ABOiKT) with ABO-compatible kidney transplantation (ABOcKT) in a singlecenter study. A total of 30 consecutive ABOiKT recipients (ABOiKTR) from April 2014 to June 2015 were included in this study. All the patients received rituximab 200 mg/body for B-cell depletion. Plasmapheresis was done for anti-ABO antibody removal. The target anti-ABO titer was kept at <1:8. The outcomes of this group of patients were compared with that of thirty ABOcKT recipients. Both the groups received similar induction therapy with antithymocyte globulin and methylprednisolone. After a follow-up period of one year, the outcomes of both the groups were compared in terms of patient survival, graft survival, graft function, incidence of rejections, infective complications, and duration of posttransplant hospital stay. The patient survival in both the groups of patients was 96.67%. The death-censored graft survival was 96.67% in both the groups. The average serum creatinine level, estimated glomerular filtration rate, incidence of rejections, infective episodes, and posttransplant hospital stay were comparable in both the groups. The outcomes of ABOiKT were comparable with ABOcKT and as such, this modality can expand the living donor pool substantially.

ABO-Incompatible Renal Transplantation with High Antibody Titer: A Case Report.

BACKGROUND Even though renal transplantation across blood groups is not uncommonly practiced nowadays, there is still hesitation regarding ABO-incompatible transplantation with very high baseline antibody titer. In this case report, the outcome of an ABO-incompatible kidney transplant recipient with a high baseline isoagglutinin titer is reported. CASE REPORT The patient was a non-diabetic, 33-year-old man with end-stage renal disease secondary to chronic glomerulonephritis. The only kidney donor available was his mother, who was blood-group incompatible. The patient's blood group was O positive, whereas his mother was B positive. We evaluated him for an ABO-incompatible renal transplant. The baseline anti-B isoagglutinin titer was >1:8196.  With a desensitization protocol of low-dose Rituximab, plasmapheresis, and IVIG, this titer was brought down to 1:32 before transplantation. He successfully underwent renal transplantation across the ABO barrier, and maintains good graft function after 1 year of follow-up.  CONCLUSIONS In the present era, a high baseline isoagglutinin titer is no longer a contraindication for successful kidney transplantation in ABO-incompatible recipient-donor pairs.

Spontaneous Renal Allograft Rupture Caused by Acute Tubular Necrosis: A Case Report and Review of the Literature.

Renal allograft rupture (RAR) is a rare but lethal complication of renal transplantation. It potentially threatens graft and patient survival. RAR is frequently associated with acute rejection, but other causes like renal vein thrombosis and acute tubular necrosis have also been observed. Most commonly a graft nephrectomy is required, but graft repair can also be attempted in selected cases to salvage the graft. Herein, we describe a rare case of spontaneous renal allograft rupture in the early posttransplant period due to acute tubular necrosis. A 42-year-old male, living donor renal allograft recipient, experienced RAR on the sixth posttransplant day. Surgical exploration showed two lacerations of 10 cm and 5 cm length at the upper and mid pole of the kidney. Histologically, the graft demonstrated acute tubular injury; no features of humoral or cellular rejection were identified. The successful management of this complication resulted in the salvage of the patient and the graft. This case demonstrates that early diagnosis and prompt treatment of a life-threatening RAR can salvage the graft.