Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.
Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.
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尿补体因子 H 在免疫球蛋白 A 肾病进展中的意义。
DOI：
10.1371/journal.pone.0126812
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhao M
中科院分区：
文献类型：
--
作者：
Liu M;Chen Y;Zhou J;Liu Y;Wang F;Shi S;Zhao Y;Wang S;Liu L;Lv J;Zhang H;Zhao M
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) 是补体系统旁路途径的重要抑制因子。该研究调查了尿液 CFH 水平对 IgAN 进展的影响。共有 351 名 IgAN 患者参与了这项研究。平均随访时间为 51.8±26.6 个月。肾脏结局被定义为复合终点，包括终末期肾病 (ESRD)、估计肾小球滤过率 (eGFR) 下降≥ 50% 或血浆肌酐水平加倍。通过酶联免疫吸附测定法测量尿 CFH 水平，并计算为尿 CFH 与肌酐的比率 (uCFH/uCr)。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 值与疾病进展相关，无论是连续 [log(uCFH/uCr)] 还是分类特征（二分变量和四分位数变量）。 Kaplan-Meier 分析显示，基线时较高的 uCFH/uCr 值预示着随访期间肾脏结果较差（对数秩，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/1.73m2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）。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。
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 351patients 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/1.73m2, 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.
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