Abstract
RATIONALE & OBJECTIVE: Recent studies have proposed that podocyte lesions within segmental glomerulosclerosis (S1) lesions are associated with kidney prognosis in immunoglobulin A nephropathy (IgAN). However, there is a lack of research exploring the effect of podocyte lesions through electron microscopy, which is currently regarded as the best power tool for evaluating podocyte injury, on kidney prognosis and response to immunosuppressive therapy (IST). STUDY DESIGN: An observational cohort study. SETTING & PARTICIPANTS: Total of 976 patients with IgAN and at least 12 months of follow-up at Peking University First Hospital. EXPOSURE: Different foot process effacement (FPE) severity evaluated by electron microscopy: mild: <50%, moderate: 50%-74%, and severe: ≥75%. OUTCOME: A composite kidney outcome of a 50% reduction in the estimated glomerular filtration rate or end-stage kidney disease. ANALYTICAL APPROACH: Cox proportional hazard models. RESULTS: Moderate and severe FPE were independent risk factors for kidney outcome in overall cohort (severe: HR, 1.85; 95% CI, 1.22-2.80; P = 0.004; moderate: HR, 1.62; 95% CI, 1.00-2.62; P = 0.048; P-trend = 0.002). Patients with moderate FPE had a significantly increased risk of worse kidney outcome among those without IST (HR, 3.04; 95% CI, 1.52-6.09; P = 0.002), with risk being significantly reduced in those with IST (HR, 1.06; 95% CI, 0.51-2.23; P = 0.87). However, severe FPE was an independent risk factor for kidney prognosis in patients with IgAN regardless of receiving IST (without IST: HR, 2.13; 95% CI, 0.97-6.09; P = 0.06; with IST: HR, 1.80, 95% CI, 1.08-2.98; P = 0.02). The reclassification ability of the model was significantly improved with 1.7% of integrated discrimination improvements (95% CI, 0.1%-5.2%) and 0.37 of continuous net reclassification improvement (95% CI, 0.14-0.62) when integrating FPE into the International IgAN Prediction Tool. LIMITATIONS: A single-center observational study, selection bias, and unmeasured confounders. CONCLUSIONS: Moderate and severe FPE were independent risk factors affecting kidney prognosis in patients with IgAN. Podocyte injury evaluated by electron microscopy had important clinical value in IgA nephropathy.