特发性膜性肾病患者血清增殖诱导配体水平的测定及临床意义

Clinical Significance of Serum a Proliferation-inducing Ligand in Patients with Idiopathic Membranous Nephropathy

背景膜性肾病(MN)是成年人肾病综合征的常见原因,目前被认为是一种抗体介导的自身免疫性疾病。增殖诱导配体(APRIL)已被证实参与多种自身免疫性疾病的发病,但其是否参与特发性膜性肾病(IMN)的发病,目前不得而知。目的检测IMN患者血清APRIL水平,探讨APRIL水平与IMN患者临床病理指标及治疗效果的关系。方法收集2015年2月-2016年2月收治于郑州大学第一附属医院肾内科108例IMN患者肾穿刺当日的10 ml全血,同时收集同时间段本院体检中心20例体检健康者10 ml全血。采用酶联免疫吸附试验(ELISA)法检测血清APRIL水平。根据IMN患者血清APRIL表达中位数,将其分为APRIL低水平表达组(n=54)与APRIL高水平表达组(n=54)。同时收集患者临床及病理资料。对患者随访6个月,根据尿蛋白转归情况将其分为有效组和无效组,比较两组APRIL水平。结果IMN患者血清APRIL水平为(14.3±4.1)μg/L,高于健康者的(7.7±4.8)μg/L(t=6.383,P<0.001)。APRIL高水平表达组尿素氮(BUN)、血肌酐(Scr)、尿酸(UA)水平均高于APRIL低水平表达组(P<0.05)。APRIL高水平表达组免疫球蛋白G(IgG)染色强度高于APRIL低水平表达组(P<0.05)。共54例患者参与随访,随访6个月后,有效组29例,无效组25例。有效组血清APRIL水平为15.7(13.0,17.9)μg/L,无效组血清APRIL水平为14.4(11.5,16.5)μg/L,两组比较,差异无统计学意义(Z=0.950,P=0.327)。结论血清APRIL水平与IMN患者疾病严重程度相关,且与IgG的肾脏沉积水平呈正相关,提示可能参与IMN疾病发生。

Background Membranous nephropathy,a common cause of nephrotic syndrome in adults,is considered to be an antibody-mediated autoimmune disease.Serum a proliferation-inducing ligand(APRIL)has been shown to be involved in the pathogenesis of a variety of autoimmune diseases,but whether it plays a role in the pathogenesis of idiopathic membranous nephropathy(IMN)is unknown.Objective To examine the relationships of APRIL level with clinicopathological manifestations,and treatment effect in patients with IMN.Methods Participants were recruited from The First Affiliated Hospital of Zhengzhou University between February 2015 and February 2016,including 108 with IMN from Department of Nephrology,and 20 sex-and age-matched health examinees from Physical Examination Center.10 ml whole blood sample was collected from IMN patients on the day of undergoing nephrocentesis,and from the controls on the same day.ELISA was used to measure serum APRIL level.By the median APRIL level,IMN patients were stratified into high APRIL expression group(n=54)and low APRIL expression group(n=54).Clinical and pathological data of IMN patients were collected.A 6-month follow-up was given to the patients,and at the end of which,urinary protein outcome was measured and was used to stratify the patients into responsive and nonresponsive groups.Mean serum APRIL level was compared between IMN and control groups,between high and low APRIL expression groups,and between responsive and nonresponsive groups.Results The mean serum APRIL level was significantly higher in IMN group compared with that of healthy controls〔(14.3±4.1)μg/L vs(7.7±4.8)μg/L,t=6.383,P<0.001〕.High APRIL expression group showed higher mean serum levels of BUN,Scr,and UA than low APRIL expression group(P<0.05).What is more,the intensity of IgG deposition in renal specimen significantly increased in high APRIL expression group compared with low APRIL expression group(P<0.05).Among the 54 patients who completed the followup,29 were responsive to the treatment,and other 25 were nonresponsive.However,there was no difference in mean APRIL level between these two groups〔15.7(13.0,17.9)μg/L vs 14.4(11.5,16.5)μg/L,Z=0.950,P=0.327〕.Conclusion Serum APRIL level was closely associated with the severity of IMN,and was positively correlated with the intensity of deposited IgG in the renal specimen,indicating APRIL may participate in the pathogenesis of IMN.