Clinicopathologic Manifestations of Immunoglobulin A Nephropathy in a Northern Indian Cohort: A Mute Assassin with Delayed Diagnosis.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, but there is a marked geographic difference in its prevalence and prognosis. IgAN is known to have an aggressive course in Asians. However, its exact prevalence and clinicopathologic spectrum in North India are not well documented. Materials and Methods: The study included all patients aged above 12 years with primary IgAN on kidney biopsy from January 2007 to December 2018. Clinical and pathological parameters were noted. Two histopathologists independently reviewed all kidney biopsies, and MEST-C score was assigned as per the Oxford classification. Results: IgAN was diagnosed in 681 (11.85%) out of 5751 native kidney biopsies. The mean age was 32 ± 12.3 years, and the male to female ratio was 2.5:1. At presentation, 69.8% had hypertension, 68% had an estimated glomerular filtration rate (eGFR) of less than 60 ml/min, 63.2% had microscopic hematuria, and 4.6% had gross hematuria. The mean proteinuria was 3.61 ± 2.26 g/day, with 46.8% showing nephrotic range proteinuria and 15.2% showing nephrotic syndrome manifestation. Histopathologically, 34.4% of patients had diffuse global glomerulosclerosis. Oxford MEST-C scoring revealed M1 in 67%, E1 in 23.9%, S1 in 46.9%, T1/T2 in 33%, and crescents in 19.6% of biopsies. The mean serum creatinine was significantly higher in cases with E1, T1/2, and C1/2 scores (P < 0.05). Hematuria and proteinuria were significantly higher (P < 0.05) with E1 and C1/2 scores. Coexisting C3 was associated with higher serum creatinine at presentation (P < 0.05). Conclusion: IgAN patients with late presentation and advanced disease became less amenable to immunomodulation in our cohort. The implementation of point-of-care screening strategies, early diagnosis, and retarding disease progression should be prioritized in the Indian strategy.

Divergent manifestations and outcomes of diffuse crescentic immunoglobulin A nephropathy and pauci-immune crescentic glomerulonephritis on long-term.

BACKGROUND: Diffuse crescentic IgAN (CIgAN) is an uncommon phenotype of IgAN, which presents as rapidly progressive renal failure, similar to patients with pauci-immune crescentic glomerulonephritis(PCGN). There are limited data on outcomes comparisons between the two. METHODS: In this single-center, retrospective cohort study, we compared the clinical features, pathological presentation, and renal outcomes of 52 patients with CIgAN and 42 patients with renal-limited PCGN from January 2007 to December 2019. RESULTS: The CIgAN patients were younger (30.5 ± 13.8 years) than PCGN patients (46.1 ± 11.8 years) (P = 0.001). The CIgAN patients had a higher prevalence of hypertension (86.5% Vs. 41.3%, P = 0.001); and degree of proteinuria (4.2 ± 2.7 g/24 h Vs. 2.3 ± 1.16 g/24 h; P = 0.001) than PCGN patients. The chronicity in terms of global glomerulosclerosis, interstitial fibrosis, and tubular atrophy was higher in the CIgAN group than in the PCGN group. The remission rate with immunosuppression was significantly higher in the PCGN group than in the CIgAN group (P = 0.016). The end-stage renal disease (ESRD) or death within 1 year of diagnosis was significantly more in the CIgAN group (62.3% Vs. 39.1%) than PCGNgroup. For patients who were dialysis-dependent at presentation, the primary outcome of ESRD or death within one year was seen in 90.9% of patients of CIgAN and 44.1% in the PCGN group (P = 0.001). The long-term death non-censored renal survival is poor in the CIgAN group than in PCGN patients. However, patient survival is poor in PCGN patients. CONCLUSION: CIgAN is a different form of RPGN compared to PCGN and carries a poor prognosis despite similar immunosuppressive therapy in the long term.

Two Decades Outcomes of Posttransplant Immunoglobulin A Nephropathy in Live Donor Renal Transplantation.

Background: The data on long-term outcomes of posttransplant immunoglobulin A nephropathy (IgAN) are confounding and vary with geography and ethnicity worldwide. We aimed to study the long-term graft outcomes of patients with posttransplant IgAN in the northern Indian cohort. Methods: The long-term graft outcomes of 51 live donor renal transplant recipients with biopsy-proven posttransplant IgAN (recurrence/de novo) were analyzed. The risk factors for graft failure in the posttransplant IgA groups were analyzed using the Cox regression analysis. Results: Out of the total of 51 patients who had posttransplant IgAN, 40 patients had a biopsy-proven native kidney IgAN. The mean duration of the clinical presentation of posttransplant IgAN was 62.4 months (5.2 years) posttransplant. Proteinuria at the time of biopsy was 3.03 ± 2.2 g/day, and 41.2% had proteinuria of more than 3 g/day at the time of biopsy. The estimated 1, 5, 10, and 20 years patient survival was 98%, 95.4%, 75.9%, and 25.2%, respectively, and the estimated 1, 5, 10, and 20 years graft survival was 98%, 88.5%, 44.6%, and 11.9%, respectively, in patients who had posttransplant IgA. Many of the traditional risk factors associated with progression in native kidney IgAN, such as the degree of proteinuria, Oxford MEST (mesangial and endocapillary hypercellularity, segmental sclerosis, and interstitial fibrosis/tubular atrophy) scoring, recipient's age, and sex were not predictive of early graft failure among patients with posttransplant IgAN. In our cohort, the only significant graft failure predictor was serum creatinine at 5 years. Chronic antibody-mediated rejection (ABMR) was seen in 21.6% of patients with posttransplant IgAN. Whether this coexistence of chronic ABMR is an incidental finding or posttransplant IgAN predisposes to chronic ABMR requires further investigation. Conclusion: Posttransplant IgAN is associated with poor long-term graft outcomes in live donor renal transplants. Proteinuria and MEST scoring were not predictive of graft failure in living donor posttransplant IgAN.