C3 glomerulopathy. Clinical predictors of long-term outcomes

Abstract

Background. C3 glomerulopathy is a rare glomerular disease characterized by dysregulation of the alternative complement pathway. Its clinical course is often unpredictable, with an increased risk of progression to chronic kidney disease. Identifying prognostic factors is essential for disease management. Objective(s). To systematically review the literature to identify clinical and laboratory predictors of long-term prognosis in C3 glomerulopathy in both pediatric and adult populations. Materials and methods. A systematic search was conducted in PubMed, Scopus, and Web of Science, including articles published between 2005 and 2024. A total of 42 studies were selected that reported the clinical course of patients with C3 glomerulopathy in relation to clinical, histological, and laboratory parameters associated with the disease. Results. A comparative review of selected studies reveals that proteinuria over 3.5 g/day, reduced eGFR (<60 ml/min/1.73 m²) at diagnosis, and persistently low serum C3 levels are strongly associated with adverse renal outcomes. Chronic histological changes, such as interstitial fibrosis and tubular atrophy, significantly correlate with the risk of progression to end-stage renal disease. Favorable response to immunosuppressive treatment was mainly seen in cases with early clinical remission and normalized complement levels. Recent research also supports the relevance of complement activation biomarkers for risk stratification and monitoring. Conclusion(s). Clinical and paraclinical predictors such as severe proteinuria, reduced glomerular filtration, and persistent hypocomplementemia are relevant predictors of renal prognosis. Their regular evaluation may guide therapeutic decisions and long-term monitoring in C3 glomerulopathy.