Impact of immunosuppressive therapy on renal and patient survival in rapidly progressive secondary IgA nephropathy

Abstract Background Secondary IgA nephropathy (IgAN) associated with systemic diseases represents a heterogeneous population in whom renal prognosis and treatment response are poorly defined. Patients with secondary IgAN have been excluded from major trials, and the benefit of adding immunosuppressive therapy to supportive care remains uncertain. Methods We conducted a retrospective multicenter cohort study including adults with biopsy-proven rapidly progressive secondary IgAN. Patients received supportive care alone, supportive care plus corticosteroids, or corticosteroids with additional immunosuppression. To address confounding by indication, inverse probability of treatment weighting based on propensity scores was applied, defining treatment escalation as immunosuppressive therapy beyond corticosteroids. Exposure was defined using landmark analyses (primary 30-day; sensitivity 14-day) to reduce immortal time bias. The primary outcome was kidney failure, accounting for death as a competing event. All-cause mortality was assessed using weighted Cox models. Results Ninety-two patients were included (mean age 61 ± 16 years; 83% male). Mean eGFR at presentation was 17±10 mL/min/1.73 m², and 32% required dialysis. Liver disease was the most frequent underlying condition (51%). Over a median follow-up of 36 months, 32 patients (35%) developed kidney failure and 34 (37%) died. After weighting, baseline covariates were balanced. Treatment escalation was not associated with progression to kidney failure (30-day landmark: subdistribution hazard ratio [SHR] 1.09, 95% confidence interval [CI] 0.35–3.38; 14-day landmark: SHR 1.40, 95% CI 0.49–4.03) or all-cause mortality (30-day: hazard ratio [HR] 1.20, 95% CI 0.34–4.17; 14-day: HR 1.14, 95% CI 0.32–4.08). Renal survival differed by etiology (log-rank P = 0.006), with the poorest outcomes in liver disease–associated IgAN. Liver disease (HR 3.16, 95% CI 1.07–9.33) and dialysis at presentation (HR 4.20, 95% CI 1.44–12.28) independently predicted kidney failure. Conclusion Rapidly progressive secondary IgAN carries high renal and patient mortality. After accounting for baseline severity, competing risk, and immortal time bias, treatment escalation was not associated with improved renal or patient survival.