Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Introduction: Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Materials and Methods: Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. Results: ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. Conclusion: ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

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.

Atypical HUS Triggered by COVID-19: A Case Report.

We hereby present a case of an atypical hemolytic uremic syndrome (aHUS) precipitated by coronavirus disease 2019 (COVID-19). A 26-year-old male was diagnosed with COVID-19 and acute kidney injury. His kidney biopsy was suggestive of thrombotic microangiopathy. Five sessions of plasmapheresis were done but were discontinued in view of nonrecovery of kidney function. He was then referred for a kidney transplant. On genetic analysis, he was found to have mutations in the complement system (CFHR1 and CFHR3), which suggested this was a case of aHUS precipitated by COVID-19. In view of the high risk of recurrence of the primary disease in live-related kidney donor transplantation, he was advised for simultaneous liver and kidney transplants.

One-Year Outcomes with Use of Anti-T-Lymphocyte Globulin in Patients Undergoing Kidney Transplantation: Results from a Prospective, Multicentric, Observational Study from India.

INTRODUCTION: Large-scale Indian data on the use of anti-T-lymphocyte globulin (ATLG) (Grafalon®) as induction therapy in kidney transplantation (KT) patients is lacking. The aim of this study was to determine the 1-year patient and graft survival outcomes with the use of ATLG as induction regimen in KT. METHODS: In a prospective, multicentric, observational study, adult patients who underwent ABO-compatible KT and had received ATLG as a part of induction were included in the study. The primary outcome measure was overall survival and death-censored graft survival at 12 months. The primary safety outcome was assessed by development of infectious complications and graft rejection. RESULTS: In total, 359 patients were included in this study. The mean age was 42.77 ± 12.30 years and 83% were male. The average ATLG dose per patient was 6.2 ± 2.2 mg/kg whereas average cumulative dose per patient was 389.6 ± 149.8 mg. The rate of graft dysfunction was 13.4% of patients and 6.7% had biopsy-proven acute rejection (BPAR). There were a total of 12 (3.3%) deaths and one graft loss. Overall survival and death-censored graft survival at 12 months were 96.65% and 99.44%, respectively. The rate of infections was 13.6% with urinary tract infections being most common. CONCLUSION: ATLG at an average dose of 6 mg/kg is an effective and safe induction regimen immunosuppressant for ABO-compatible KT with favourable impact on survival and graft function in Indian patients.

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.

IgA Nephropathy with Wilson's Disease: A Case Report and Literature Review.

The most common glomerulonephritis seen in the world is immunoglobulin A nephropathy (IgAN). It can be primary or secondary associated with various conditions like Chronic Liver disease, Crohn's disease, neoplasms, etc. However, IgAN secondary to Wilson's disease is very rare. A 9 year old boy presented with gross hematuria and proteinuria. He had a history of recurrent jaundice in the past. Ultrasonography (USG) whole abdomen showed altered echotexture of the liver with normal-sized kidneys. An extended workup for liver disease was done, and the diagnosis of Wilson's disease was confirmed with decreased serum ceruloplasmin levels, increased urinary copper, and the Kayser-Fleischer ring. Urine routine microscopy showed numerous red blood cells, few red blood cell casts, and mild proteinuria. Renal biopsy showed IgAN. The patient was started on D-penicillamine. On follow-up at 3 months, he showed complete resolution of proteinuria and hematuria. Thus, we suggest that Wilson's disease should be considered as one of the causes of secondary IgAN in pediatric patients with hematuria, proteinuria with liver dysfunction.

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.

Clinical Remission of Immunoglobulin A Nephropathy after Bariatric Surgery in a Young Morbidly Obese Patient.

A 23-year-old girl with morbid obesity, diabetes mellitus, hypertension, obstructive sleep apnea, and immunoglobulin A nephropathy (IgAN) attended a bariatric clinic after multiple failed attempts at weight loss. In the past, she was diagnosed with IgAN with nephrotic syndrome and raised blood pressure at the age of 11 years. Apart from optimization of blood pressure with angiotensin receptor blocker, she required steroid to maintain her remission in initial four years which was later switched to mycophenolate mofetil (MMF). She was diagnosed with diabetes at the age of 13 years; her blood sugars remained poorly controlled despite therapy with oral hypoglycemic agents and insulin. She underwent sleeve gastrectomy with no post-operative complications. During the follow-up, she showed a steady reduction in her weight, along with maintaining normal blood sugars and pressure without medications. At 18 months of follow-up, IgAN remained in remission after stopping MMF at four months after the surgery. Obesity is considered an important cofactor in the progression of IgAN. This case highlights the importance of weight reduction to halt the progression of the disease.

Tacrolimus-induced Epidermoid Cysts in the Renal Transplant Patient.

Epidermal cysts are common benign cystic lesions that occur mostly sporadically. Common sites involved are arms, face, and trunk. The cyst may progress slowly and remain for years. These cysts arise as a result of the plugging of the follicular orifice. Etiology has largely remained unknown although local trauma, ultraviolet rays, and human papilloma virus (HPV) have been implicated in a few cases. Calcineurin inhibitors (CNIs) especially cyclosporine has been discredited for cutaneous side effects such as hirsutism and gingival hyperplasia. Epidermoid cysts have been also associated with patients with solid organ transplant recipients on cyclosporine. Tacrolimus is considered to be free of dermatological side effects. Herein, we report a case of 56-year-old renal allograft recipient on tacrolimus, who develop more than >100 epidermoid cysts over the face, trunk, back, and extremities. The lesions ceased to progress once the tacrolimus was stopped.