title: Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Urinary CFH levels are associated with renal function decline and increased urinary CFH levels are a risk factor for progression of IgA nephropathy.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Maojing
authors.initials: M
authors.lastname: Liu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Shi
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory of Electron Microscopy, Peking University First Hospital, Peking University First Hospital; Beijing 100034, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Lv
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital; Beijing 100034, China; Institute of Nephrology, Peking University; Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China; Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; Beijing 100034, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000328:Adult; D015331:Cohort Studies; D017242:Complement Factor H / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000209:etiology* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D017242:Complement Factor H