The association of 5-year therapeutic responsiveness with long-term renal outcome in IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis. Since most patients have a relatively benign renal prognosis, long-term follow-up is required. During such a long course of disease, relapse of IgAN is occasionally observed after upper respiratory tract infection or without any trigger. However, little is known about the impact of relapse on long-term renal outcomes. In this retrospective cohort study of biopsy-proven primary IgAN, we analyzed the association of 5-year therapeutic responsiveness (relapse) with the subsequent development of end-stage kidney disease (ESKD) using a 5-year landmark analysis (Cox model) and explored predictors of relapse from histological and clinical data at baseline. Among 563 patients from the exploratory cohort, most relapses (13.7%) occurred within 5 years after treatment. Using 5-year landmark analysis, among 470 patients, 79 developed ESKD during a median follow-up period of 155 months. Even after adjustment for clinicopathological relevant confounders, hazard ratios (95% confidence intervals) in the relapse and non-responder groups compared with the remission group were 2.86 (1.41–5.79) and 2.74 (1.48–5.11), respectively. Among 250 patients who achieved remission within 5 years, proteinuria, eGFR, mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, and crescent, but not interstitial fibrosis/tubular atrophy, were independent predictors of 5-year relapse in multivariable logistic regression analysis, Both relapsers and non-responders had similarly strong association with ESKD in patients with IgAN. We also confirmed the predictors of relapse 5 years after renal biopsy, which may guide the treatment strategies for patients with IgAN who occasionally relapse after remission.