Serum C4/C3 ratio at disease onset predicts end-stage renal disease in microscopic polyangiitis: the multicentre REVEAL cohort

We investigated whether serum complement C3 and C4 levels and the C4/C3 ratio at disease onset were associated with clinical features, renal involvement, and prognosis in microscopic polyangiitis (MPA). Patients were stratified into tertiles according to baseline C3 and C4 levels. Associations with end-stage renal disease (ESRD) were assessed using multivariable Cox regression and sensitivity analyses accounting for treatment-related factors, missing data, and competing risk. Five-year time-dependent receiver operating characteristic analysis evaluated discrimination for ESRD. Among 308 patients included in the C3 analysis and 264 in the C4 analysis, the low C3 tertile had higher serum creatinine levels, more frequent rapidly progressive glomerulonephritis, a higher incidence of ESRD, and poorer overall survival. C4 tertiles were not associated with renal outcomes or survival. A higher C4/C3 ratio was associated with an increased risk of ESRD in multivariable analysis, with generally consistent effect directions across sensitivity analyses. Its 5-year discriminatory performance was comparable to that of C3 alone (area under the curve, 0.718 vs. 0.739), with higher specificity (0.775 vs. 0.662). The C4/C3 ratio may serve as a complementary marker for renal risk stratification in MPA.