Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy

• Published in: PloS one 2015-06, Vol.10 (6), p.e0126812-e0126812
• Main Authors: Liu, Maojing, Chen, Yuqing, Zhou, Jingjing, Liu, Ying, Wang, Fengmei, Shi, Sufang, Zhao, Yanfeng, Wang, Suxia, Liu, Lijun, Lv, Jicheng, Zhang, Hong, Zhao, Minghui
• Format: Article
• Language: English
• Subjects: Adult; Alternative pathway; Biopsy; Blood pressure; Cohort Studies; Complement; Complement activation; Complement factor H; Complement Factor H - urine; Creatinine; Development and progression; Disease prevention; Education; End-stage renal disease; Enzyme-linked immunosorbent assay; Epidermal growth factor receptors; Evaluation; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA - complications; Glomerulonephritis, IGA - etiology; Glomerulonephritis, IGA - mortality; Health aspects; Hospitals; Humans; Iga glomerulonephritis; IgA nephropathy; Immunoglobulin A; Immunoglobulins; Immunosuppressive agents; Kaplan-Meier Estimate; Kidney diseases; Kidney Failure, Chronic - etiology; Kidney Failure, Chronic - mortality; Laboratories; Male; Medical prognosis; Medicine; Middle Aged; Nephrology; Pathogenesis; Proteinuria; Renal function; Risk factors; ROC Curve; Rodents; Statistical models; Subgroups; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126812

After activation, the complement system is involved in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Complement factor H (CFH) is a crucial inhibitory factor of the alternative pathway of the complement system. The study investigated the effects of urinary CFH levels on IgAN progression. A total of 351 patients with IgAN participated in this study. They were followed up for an average of 51.8 ± 26.6 months. Renal outcome was defined as a composite endpoint, that included instances of end-stage renal disease (ESRD), ≥ 50% decline in estimated glomerular filtration rate (eGFR) or doubling of plasma creatinine levels. Urinary CFH levels were measured by enzyme-linked immunosorbent assay and calculated as the ratio of urinary CFH over creatinine (uCFH/uCr). In the whole cohort, uCFH/uCr values were associated with disease progression either as continuous [log(uCFH/uCr)] or categorical traits (dichotomous and quartile variables) after adjusting for eGFR, proteinuria, mean arterial blood pressure, histological grading and immunosuppressive therapy in the Cox proportional hazard model. Kaplan-Meier analysis showed that higher uCFH/uCr values at baseline predicted worse renal outcome during follow-up (log-rank, P < 0.001). Receiver operating characteristic curve (ROC) analysis showed that log(uCFH/uCr) had predictive value for renal outcome (area under curve [AUC] = 0.745), and the AUC increased to 0.805 after being incorporated into baseline eGFR and proteinuria. In subgroup analysis with eGFR ≥ 60 mL/min/1.73 m2, log(uCFH/uCr) had better predictive value (AUC = 0.724, P = 0.002) for renal outcome compared to eGFR (AUC = 0.582, P = 0.259) and proteinuria (AUC = 0.615, P = 0.114). Urinary CFH levels are associated with renal function decline and increased urinary CFH levels are a risk factor for progression of IgA nephropathy.