Glomerular C4d Deposition and Kidney Disease Progression in IgA Nephropathy: A Systematic Review and Meta-analysis

Abstract Background Glomerular deposition of C4d is a widely used biomarker for activation of the lectin pathway in the complement system and is reported to be associated with kidney progression in IgA nephropathy (IgAN). The aim of this study was to evaluate whether glomerular C4d deposition, as a new biomarker, improves the prediction of kidney prognosis in IgAN. Study Design Systematic review and meta-analysis. Setting & Population Patients with biopsy-proven primary IgAN without age limitations. Selection Criteria for Studies Cross-sectional or cohort studies reporting the prevalence of glomerular C4d deposition or evaluating its association with IgAN progression. Predictor Glomerular C4d deposition. Outcome Composite progression event of more than a 30% decline in the estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results Twelve studies with 1,251 patients were included. The prevalence of glomerular C4d deposition was 34% (95% CI, 27%-41%), with large heterogeneity (I2 = 86, P Limitations The definition of positive C4d was not uniform, and not all studies provided data about kidney outcomes. Conclusions Glomerular C4d deposition is associated with an adverse prognosis and may be a useful biomarker of disease prediction in IgAN.