Espinosa Mario, Ortega Rosa, Sánchez Marina, Segarra Alfons, Salcedo Maria Teresa, González Fayna, Camacho Rafael, Valdivia Miguel Angel, Cabrera Rocio, López Katia, Pinedo Fernando, Gutierrez Eduardo, Valera Alfonso, Leon Miryam, Cobo Maria Angeles, Rodriguez Rosa, Ballarín Jose, Arce Yolanda, García Beatriz, Muñoz María Dolores, Praga Manuel
Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
Clin J Am Soc Nephrol. 2014 May;9(5):897-904. doi: 10.2215/CJN.09710913. Epub 2014 Feb 27.
Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-to-perform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included 283 patients with IgAN in 11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The primary predictor was mesangial C4d staining. Secondary predictors included demographic, clinical, and laboratory characteristics, and Oxford pathologic classification criteria. The primary end point was the cumulative percentage of patients who developed ESRD, defined as onset of chronic dialysis or renal transplantation. C4d was analyzed by immunohistochemical staining using a polyclonal antibody. Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate the effect of C4d staining on renal survival.
There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as C4d positive and C4d negative, respectively. Renal survival at 20 years was 28% in C4d-positive patients versus 85% in C4d-negative patients (P<0.001). Independent risk factors associated with ESRD were as follows: proteinuria (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95% CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m(2) increase, 0.96; 95% CI, 0.94 to 0.97; P<0.001), T2 Oxford classification (tubular atrophy/interstitial fibrosis, >50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01), and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01).
C4d-positive staining is an independent risk factor for the development of ESRD in IgAN. This finding is consistent with the possibility that complement activation is involved in the pathogenesis of this disease.
多项研究表明，补体系统激活是IgA肾病（IgAN）的一种致病机制。C4d染色是一种用于肾活检分析的廉价且易于操作的方法。本研究旨在评估C4d染色在IgAN中的临床及预后意义。
设计、地点、参与者及测量方法：这项回顾性队列研究纳入了西班牙11家医院中1979年至2010年间接受肾活检的283例IgAN患者。主要预测指标是系膜C4d染色。次要预测指标包括人口统计学、临床和实验室特征以及牛津病理分类标准。主要终点是发展为终末期肾病（ESRD）患者的累积百分比，ESRD定义为开始慢性透析或肾移植。使用多克隆抗体通过免疫组化染色分析C4d。采用Kaplan-Meier法和Cox比例风险分析法评估C4d染色对肾脏生存的影响。
分别有109例（38.5%）和174例（61.5%）患者被分类为C4d阳性和C4d阴性。C4d阳性患者20年时的肾脏生存率为28%，而C4d阴性患者为85%（P<0.001）。与ESRD相关的独立危险因素如下：蛋白尿（每增加1 g/d的风险比[HR]为1.16；95%置信区间[95%CI]为1.03至1.31；P=0.01）、估算肾小球滤过率（eGFR）（每1.73 m²每分钟增加1 ml/min的HR为0.96；95%CI为0.94至0.97；P<0.001）、牛津分类法中的T2（肾小管萎缩/间质纤维化>50%；HR为4.42；95%CI为1.40至13.88；P=0.01）以及C4d阳性染色（HR为2.45；95%CI为1.30至4.64；P=0.01）。
C4d阳性染色是IgAN患者发生ESRD的独立危险因素。这一发现与补体激活参与该疾病发病机制的可能性相符。
