肾小球补体C1q及C3c沉积与糖尿病肾病进展的相关性分析

Association of complement C3c and C1q deposition in glomeruli with the progression of diabetic kidney disease

目的探讨肾小球补体C1q及C3c沉积与糖尿病肾病进展的相关性。方法纳入2011年1月至2019年7月在南京医科大学第一附属医院确诊的2型糖尿病肾病患者112例,其中男性83例(74.1%),年龄(51.22±11.12)岁,随访时间19.0(8.5,31.3)个月。根据肾小球C1q和C3c是否沉积分为四组:C1q无沉积C3c无沉积组(n=38)、C1q无沉积C3c沉积组(n=24)、C1q沉积C3c无沉积组(n=14)和C1q沉积C3c沉积组(n=36),检测24 h尿蛋白等临床指标并收集病理资料。采用Cox回归及Kaplan-Meier生存曲线评估肾C1q和C3c沉积对肾脏预后的影响。结果四组间24 h尿蛋白差异有统计学意义[分别为1.84(0.92,3.89),4.19(2.09,6.50)3.30(1.84,6.70),3.64(2.49,7.22)g/24 h,P<0.01],C1q沉积C3c沉积组24 h尿蛋白定量显著高于C1q无沉积C3c无沉积组(P<0.01)。Kaplan-Meier生存曲线结果提示,四组累积生存率差异有统计学意义(Log-rankχ²=8.785,P<0.05),C1q沉积C3c无沉积组累计生存率最低,预后最差。调整后的多因素Cox分析显示,肾小球C1q和C3c共沉积[风险比(HR)2.260,95%可信区间1.329~3.845,P<0.01]、肾小球C1q+C3c+IgM均沉积(HR=4.142,95%可信区间1.071~16.021,P<0.05)是肾脏预后的独立危险因素。结论肾小球C1q及C3c沉积与糖尿病肾病患者蛋白尿、较差的肾功能和预后不良相关,且肾小球C1q和C3c共沉积是糖尿病肾病进展的独立危险因素。

Objective To explore the association of glomerular deposition of complement C3c and C1q with baseline clinicopathological characteristics and the prognosis of type 2 diabetic patients with diabetic kidney disease(DKD).Methods A total of 112 patients with DKD diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2011 to July 2019 were recruited in this study.Among them,83 patients(74.1%)were males.The average age were(51.22±11.12)years with 19.0(8.5,31.3)months of follow-up.According to the glomerular deposition of C1q and C3c,all patients were divided into four groups:C1q non-deposited and C3c non-deposited group(n=38),C1q non-deposited but C3c deposited group(n=24),C1q deposited but C3c non-deposited group(n=14)and C1q deposited and C3c deposited group(n=36).Clinical indicators such as 24 h urine protein were detected and pathological data were collected.Cox regression and Kaplan-Meier survival curve were used to evaluate the effect of renal C1q and C3c deposition on renal prognosis.Results There were significant differences of 24 h urine protein among the four groups[1.84(0.92,3.89),4.19(2.09,6.50),3.30(1.84,6.70),3.64(2.49,7.22)g/24 h,respectively,P<0.01].The 24 h urine protein in C1q deposited and C3c deposited group was significantly higher than that in C1q non-deposited and C3c non-deposited group(P<0.01).Kaplan-Meier survival curve results showed that the cumulative survival rates of the four groups were statistically different(Log-rankχ²=8.785,P<0.05),and C1q deposited but C3c non-deposited group had the lowest cumulative survival rate and the worst prognosis.Adjusted multivariate Cox analysis showed that both the co-deposition of glomerular C1q and C3c(hazard ratio=2.260,95%confidence interval was 1.329-3.845,P<0.05)and glomerular C1q+C3c+IgM(hazard ratio=4.142,95%confidence interval was 1.071-16.021,P<0.05)were independent risk factors for renal prognosis.Conclusion Glomerular C3c and C1q deposition are associated with deteriorated renal function and prognosis in patients with DKD.Glomerular C1q and C3c co-deposition is an independent risk factor for DKD progression.