血清补体C4和C3浓度的比值在预测IgAN不良预后中的价值研究

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (8): 881-886.

血清补体C4和C3浓度的比值在预测IgAN不良预后中的价值研究

周琼秀，章建娜，尤小寒，吕吟秋，陈波，张骥

温州医科大学附属第一医院肾内科，温州 325000，浙江

收稿日期:2017-03-14 修回日期:2017-04-30 出版日期:2017-08-26 发布日期:2017-08-18
通讯作者: 温州市科技局（Y20130208，Y20130271）
作者简介:周琼秀，女，硕士，住院医师，研究方向：IgA肾病的临床及基础研究。 Tel：13736967768 E-mail：mingyxiu@126.com
基金资助:
温州市科技局（Y20130208，Y20130271）

Serum C4/C3 ratio in predicting the adverse prognosis of IgA nephropathy

ZHOU Qiongxiu, ZHANG Jianna, YOU Xiaohan, LV Yinqiu, CHEN Bo, ZHANG Ji

Nephrology Department, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

Received:2017-03-14 Revised:2017-04-30 Online:2017-08-26 Published:2017-08-18

摘要/Abstract

摘要：

目的: 探索血清补体水平与IgA肾病(IgAN)患者肾脏预后的关系。方法: 回顾性分析2009-2013年在本院确诊的原发性IgAN患者，记录患者人口学数据、临床实验室检查、肾活检病理学及随访结果。计算血清补体C4与C3浓度的比值（C4/C3比值，标为C.ratio）。采用多种统计学方法探索C.ratio和肾脏预后间的关系。所有统计采用R软件及相关软件包计算。结果: 总共入组206例患者，中位随访时间为（37.2±6.5）月，其中男性患者88例，占42.8%。比较肾脏不同病理改变和C.ratio的关系显示系膜细胞增生，节段性肾小球硬化或粘连，肾小管萎缩或肾间质纤维化的患者C.ratio水平较高。受试者工作特征曲线 (ROC)显示C.ratio能够有效鉴别肾病不良预后，曲线下面积为0.735，最佳截点为0.25（敏感度和特异度分别为70.9%和72.2%），以该截点为参照，C.ratio大于上述截点的患者舒张压高、24 h尿蛋白定量较多。将患者年龄、性别、舒张压、收缩压及24 h尿蛋白定量等因素纳入进行校正后，Kaplan-meier生存曲线显示高C.ratio组的肾脏预后显著差于低C.ratio组，风险比为5.1（95%CI：1.9-13.9,P=0.001）。结论: 血清补体水平的比值C.ratio和IgAN患者肾脏的不良预后显著相关，可以作为临床判断IgAN不良预后的临床预测因子。

关键词: IgAN, 补体C3, 补体C4

Abstract:

AIM: To investigate the relationship between serum complement levels and prognosis of IgA nephropathy. METHODS: Patients diagnosed through renal biopsy as primary IgA nephropathy from 2009 to 2013 in our hospital were recruited into this retrospective study. Baseline demographic, clinical laboratory examination, renal biopsy and histopathology examination, as well as the follow-up results were reviewed. The ratio of serum complement C4 to C3 (C4/C3 ratio, marked as C. ratio) was calculated. Multiple statistical methods were used to investigate the relationship between C. ratio and nephropathy prognosis. All statistics were calculated using R software and related software packages. RESULTS:A total of 206 patients were enrolled in the present study, and the median follow-up time was (37.2±6.5) months. There were 88 (42.8%) male patients. The comparison of different pathological changes of nephropathy with C.ratio showed that the C.ratio levels were significantly higher in mesangial hypercellularity, segmental fibrosis/adhesion, and interstitial fibrosis/tubular atrophy. ROC curve showed that C.ratio could effectively identify the adverse prognosis of IgA nephropathy, the area under the ROC curves was 0.735 for C.ratio, with a cut-off value of 0.25 (sensitivity: 70.9%, specificity: 72.2%). In addition, higher C.ratio (>0.25) was associated with higher diastolic blood pressure, and greater proteinuria. Kaplan-meier survival analysis also confirmed that patients with higher level of C.ratio had significantly poorer nephropathy prognosis after adjusted by age, gender, blood pressure and urine protein, the Hazard Ratio was 5.1(95%CI, 1.9-13.9, P=0.001). CONCLUSION: High level of serum C4 to C3 ratio was significantly associated with poor prognosis of IgA nephropathy; this could be used as a clinical prognosis predictor in IgA nephropathy patients.

Key words: IgA nephropathy, complement C3, complement C4

中图分类号:

R965.2

周琼秀，章建娜，尤小寒，吕吟秋，陈波，张骥. 血清补体C4和C3浓度的比值在预测IgAN不良预后中的价值研究[J]. 中国临床药理学与治疗学, 2017, 22(8): 881-886.

ZHOU Qiongxiu, ZHANG Jianna, YOU Xiaohan, LV Yinqiu, CHEN Bo, ZHANG Ji . Serum C4/C3 ratio in predicting the adverse prognosis of IgA nephropathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(8): 881-886.

参考文献

［1］Roos A, Rastaldi MP, Calvaresi N, et al.Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease［J］. J Am Soc Nephrol, 2006, 17(6): 1724-1734.
［2］Montanés Bermúdez R, Bover Sanjuán J, Oliver Samper A, et al.Assessment of the new CKD-EPI equation to estimate the glomerular filtration rate［J］. Nefrologia, 2010, 30(2): 185-194.
［3］Daha MR, van Kooten C. Role of complement in IgA nephropathy［J］.J Nephrol, 2016, 29(1): 1-4.
［4］Maillard N, Wyatt RJ, Julian BA,et al.Current Understanding of the Role of Complement in IgA Nephropathy［J］. J Am Soc Nephrol, 2015, 26(7): 1503-1512.
［5］Kim SJ, Koo HM, Lim BJ, et al. Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy［J］. PLoS One, 2012,7(7): e40495.
［6］Ibels LS, Gyory AZ.IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature［J］. Medicine (Baltimore), 1994，73(2): 79-102.
［7］Mizerska-Wasiak M, Maldyk J, Rybi-Szumińska A, et al.Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy［J］. Pediatr Nephrol, 2015,30(7): 1207.
［8］章晓炎，谢静远，陈楠, 补体C3系膜区沉积与低C3血症在IgAN中的意义［J］.中华肾脏病杂志, 2014, 30(3): 187-194.
［9］Yang X, Wei RB, Wang Y, et al.Decreased serum C3 levels in immunoglobulin A (IgA) nephropathy with chronic kidney disease: a propensity score matching study［J］.Med Sci Monit, 2017, 23: 673-681.
［10］Zhu B, Zhu CF, Lin Y, et al.Clinical characteristics of IgA nephropathy associated with low complement 4 levels［J］. Ren Fail, 2015, 37(3): 424-432.
［11］Foltz CJ, Cork LC, Winkelstein JA.Absence of glomerulonephritis in guinea pigs deficient in the fourth component of complement［J］.Vet Pathol, 1994, 31(2): 201-206.
［12］ Kouki P, Marsh JE, Sacks SH,et al. Autoimmune renal injury in C3- and C4-deficient mice: a histological and functional study［J］.Nephron Exp Nephrol, 2004, 96(1): e14-22.
［13］Onda K, Ohsawa I, Ohi H,et al. Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function［J］.BMC Nephrol, 2011,12: 64.
［14］Onda K, Ohi H, Tamano M, et al.Hypercomplementemia in adult patients with IgA nephropathy［J］. J Clin Lab Anal, 2007, 21(2): 77-84.
［15］Roos A, Bouwman LH, van Gijlswijk-Janssen DJ, et al.Human IgA activates the complement system via the mannan-binding lectin pathway［J］. J Immunol, 2001, 167(5): 2861-2868.
［16］杨晋辉，李祥金.乙型病毒性肝炎患者血清补体C3、补体C4的临床意义［J］.临床肝胆病杂志, 2007,23(5): 355-356.