摘要
目的·探讨IgA肾病(IgAN)患者肾组织H因子(CFH)沉积的临床病理特征及预后的相关性。方法·纳入上海交通大学医学院附属瑞金医院肾脏科肾脏穿刺确诊随访1年以上的原发性IgAN患者。采用免疫组织化学检测患者肾组织CFH沉积,酶联免疫吸附方法检测血清CFH水平。记录患者基线临床、病理资料及预后情况。研究终点定义为eGFR下降30%或eGFR<15mL/(min·1.73 m^2)或接受肾脏替代治疗。结果·共入选283例IgAN患者,肾脏病理检査示198例(70%)患者伴有CFH沉积。CFH沉积阳性的患者尿蛋白排泄增多、血尿酸增高,肾脏病理示系膜细胞增生、节段硬化及肾小管萎缩/间质纤维化更严重。肾组织CFH沉积与血清CFH之间无显著相关性。CFH沉积阳性患者的疾病无进展时间较阴性患者明显缩短[(59.90±1.87)个月vs(65.10±1.78)个月,P=0.01]。多元COX回归分析在校正基线eGFR、收缩压、白蛋白和血红蛋白后,CFH沉积仍为IgAN疾病进展的独立危险因素(HR=2.54,95%:CI1.04~6.17)。结论·CFH沉积阳性患者临床病理表现较沉积阴性患者严重、预后差,提示补体旁路局部活化而非全身活化可加重IgAN进展。
Objective · To investigate the association between clinicopathologic features of H factor （CFH） deposition in renal tissue of patients with IgA nephropathy （IgAN） and the prognosis. Methods · The primary IgAN patients who were confirmed by renal biopsy and were followed for at least 1 year by the Department of Nephrology at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine were enrolled. CFH deposition in renal tissue was detected by immunohistochemistry. Serum CFH level was measured by Enzyme Linked Immunosorbent Assay （ELISA）. The baseline clinical data, pathological data, and prognosis were recorded. The end point of the study was defined as a decrease in eGFR by 30% or eGFR〈15 mL/（min · 1.73 m2） or receiving renal replacement therapy. Results · A total of 283 patients with IgAN were recruited. Renal pathological examinations revealed that 198 （70%） of them had CFH deposition in renal tissue. Patients with positive CFH deposition had higher urine protein excretion and serum uric acid levels and renal pathology showed severer mesangial proliferation, segmental sclerosis, and interstitial fibrosis. The association between CFH deposition in renal tissue and serum CFH deposition was not significant. Kaplan-Meier analysis found that the progression-free time was significantly shorter in patients with positive CFH deposition than in patients without CFH deposition [（59.90±1.87） months vs （65.10±1.78） months, P=0.01]. Multivariate Cox regression analysis showed that CFH deposition was still an independent risk factor for IgAN progression after adjustment of baseline eGFR, hemoglobin, systolic blood pressure, and serum albumin （HR=2.54, 95% CI： 1.04-6.17）. Conclusion · Patients with positive CFH deposition have severer clinical manifestations and poorer prognosis as compared with patients without CFH deposition, suggesting the local activation of alternative complement pathway rather than systemic activation can promote the progression of IgAN.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2016年第8期1144-1149,共6页
Journal of Shanghai Jiao tong University:Medical Science
基金
国家重点基础研究发展计划(2012CB517604)
国家自然科学基金(81370015,81570598)
上海市教育委员会高峰高原学科建设计划(20152207)
上海市科学技术委员会国际合作交流项目(14430721000)
国家临床重点专科建设和上海市卫生局重中之重学科建设基金~~
关键词
IGA肾病
补体旁路活化
补体H因子
疾病进展
IgA nephropathy
complement alternative pathway
complement factor H
disease progression
