尿补体因子H在免疫球蛋白A肾病进展中的作用
Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.
作者信息
Liu Maojing, Chen Yuqing, Zhou Jingjing, Liu Ying, Wang Fengmei, Shi Sufang, Zhao Yanfeng, Wang Suxia, Liu Lijun, Lv Jicheng, Zhang Hong, Zhao Minghui
机构信息
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.
Laboratory of Electron Microscopy, Peking University First Hospital, Peking University First Hospital; Beijing 100034, China.
出版信息
PLoS One. 2015 Jun 2;10(6):e0126812. doi: 10.1371/journal.pone.0126812. eCollection 2015.
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.
背景
激活后，补体系统参与免疫球蛋白A肾病（IgAN）的发病机制。补体因子H（CFH）是补体系统替代途径的关键抑制因子。本研究调查了尿CFH水平对IgAN进展的影响。
方法
共有351例IgAN患者参与本研究。他们平均随访51.8±26.6个月。肾脏结局定义为一个复合终点，包括终末期肾病（ESRD）、估计肾小球滤过率（eGFR）下降≥50%或血浆肌酐水平翻倍的情况。采用酶联免疫吸附测定法测量尿CFH水平，并计算为尿CFH与肌酐的比值（uCFH/uCr）。
结果
在整个队列中，在Cox比例风险模型中调整eGFR、蛋白尿、平均动脉血压、组织学分级和免疫抑制治疗后，uCFH/uCr值作为连续变量[log(uCFH/uCr)]或分类特征（二分法和四分位数变量）与疾病进展相关。Kaplan-Meier分析显示，基线时较高的uCFH/uCr值预测随访期间肾脏结局较差（对数秩检验，P<0.001）。受试者工作特征曲线（ROC）分析显示，log(uCFH/uCr)对肾脏结局具有预测价值（曲线下面积[AUC]=0.745），纳入基线eGFR和蛋白尿后，AUC增加至0.805。在eGFR≥60 mL/min/1.73 m2的亚组分析中，与eGFR（AUC=0.582，P=0.259）和蛋白尿（AUC=0.615，P=0.114）相比，log(uCFH/uCr)对肾脏结局具有更好的预测价值（AUC=0.724，P=0.002）。
结论
尿CFH水平与肾功能下降相关，尿CFH水平升高是IgA肾病进展的危险因素。
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