Circulating alternative pathway complement cleavage factor Bb is associated with vascular lesions and outcomes in IgA nephropathy.

Abstract

Complement alternative pathway (AP) activation is linked to immunoglobulin A nephropathy (IgAN) prognosis severity, but Bb fragment's role is unclear. We examined the relationship between serum Bb fragment concentration at IgAN diagnosis with disease activity and outcomes. This retrospective study included 125 biopsy-proven IgAN patients (age 39.9 years, 75% male, eGFR 82mL/min, proteinuria 0.5g/day) enrolled from 1984 to 2010 and followed for a minimum of 18 months. Monitoring continued until the last follow-up, end-stage kdiney disease (ESKD), or death. Serum Bb fragment was measured using ELISA at diagnosis. Oxford classification and global optical score (GOS) were utilized for pathology assessment. Patients were followed for a median of 16 years, 42% developed CKD stage 3 or higher, 19% reached ESKD, and 9% died. Serum Bb fragment concentration negatively correlated with eGFR values at last follow-up and positively with vascular and tubular histopathological indices. In univariate Cox regression analyses, higher Bb fragment concentration was associated with ESKD alongside older age, increased body-mass-index, arterial hypertension, lower eGFR, higher proteinuria, E1, S1, T1-2, GOS, and corticotherapy. Patients with Bb levels≥14.3μg/mL had shorter mean kidney survival time (19.5vs 22.7 years, p=0.07); after adjusting for progression risk factors, the association persisted (HR 4.76, 95% CI 1.56-14.43). Serum Bb fragment concentration at diagnosis may predict long-term IgAN outcomes, potentially due to AP activation at the endothelial surface. Further research is needed to confirm these results and evaluate Bb fragment's role in IgAN management.