原发性肾病综合征患儿血清及尿液中血管生成素样蛋白3和4的临床意义

Clinical significance of serum and urine angiopoietin- like 3 and 4 in children with primary nephrotic syndrome

目的初步探讨血清与尿液中血管生成素样蛋白3（ANGPTL3）和4（ANGPTL4）在原发性肾病综合征（PNS）中的临床意义。方法收集2012年9月至2013年8月复旦大学附属儿科医院肾脏风湿科PNS住院患儿180例为研究对象，纳入健康体检儿童18例为对照组。运用酶联免疫吸附法（ELISA）检测血清及尿液样本中ANGPTL3和4的浓度；采用全自动生化分析仪检测尿蛋白（up）、尿肌酐（Ucr）、血肌酐（Scr）、血尿素氮（BUN）、三酰甘油（TG）及总胆固醇（TC）浓度；采用SPSS19．0软件进行统计分析。结果（1）PNS患儿血ANGPTL3的水平高于健康儿童[1210．95（671．28～1571．87）μg／L比308．20（230．05～372．26）μg／L，P〈0．011；PNS患儿尿ANGPTL4／Cr的水平高于健康儿童[115．57（26．50～129．81）ng／g比11．26（2．23～15．11）ng／g，P〈0．01]；PNS患儿尿ANGPTL3／Cr值及血ANGPTL4水平与健康儿童相比差异均无统计学意义。（2）PNS患儿组血ANGPTL3水平和发病年龄（r=0．199，P=0．047）、病程（r=0．501，P=0．027）、24h尿蛋白量（r=0．384，P=0．004）、Up／Ucr（r=0．367，P=0．006）、TG（r=0．314，P=0．021）及TC（r=0．444，P=0．001）呈正相关；控制血脂因素后，PNS患儿血ANGPTL3仍与24h尿蛋白量（r=0．348，P〈0．001）、Up／Ucr（r=0．312，P〈0．001）呈正相关；尿ANGPTL4／Cr与24h尿蛋白量（r=0．318，P=0．019）及Up／Ucr（r=0．117，P=0．044）呈正相关。（3）ANGPTL3和ANGPTL4水平与PNS激素治疗反应及复发情况无相关性，然而同一例激素依赖频复发NS患儿在激素治疗的不同时期，血ANGPTL3水平变化与尿蛋白变化趋势一致。（4）在蛋白尿程度、血脂水平相对一致的前提下，PNS患儿中，病理类型不同，其血ANGPTL3水平也不同。结论血ANGPTL3水平可能是反映PNS发病情况、蛋白尿程度、病理类型及激素药物治疗后蛋白尿转归的重要指标之一。尿ANGPTL4水平与PNS患儿尿蛋白水平正相关，可能也具有一定的临床参考价值。

Objective To explore the clinical significance of the serum and urine angiopoietin （ANGPTL） 3 and 4 levels in children with primary nephrotic syndrome （PNS）. Methods Serum and urine samples from 180 children with PNS admitted from September 2012 to August 2013, and from 18 healthy children as control, were analyzed. Serum and urine ANGPTL3 and 4 concentrations were detected by ELISA. Urine protein （Up）, urine creatinine （Ucr）, serum creatinine （Scr）, blood urea nitrogen （BUN）, triglyceride （TG） and total cholesterol （TC） levels were analyzed by automatic biochemical analyzer. Data were analyzed by SPSS 19.0. Results （1） Serum ANGPTL3 concentration in PNS children was higher than that in healthy children population [1210.95 （671.28- 1571.87） μg/L vs 308.20 （230.05- 372.26）μg/L, P 〈 0.01]; Urine ANGPTIA/Cr in PNS children was also higher than that in healthy children [115.57 （26.50-129.81） ng/g vs 11.26 （2.23-15.11） ng/g, P 〈 0.01]; Serum ANGPTIA concentration and urine ANGPTL3/Cr in PNS children had no difference with those in healthy children population. （2） ANGPTL3 serum levels were positively correlated with age at onset （r=0.199, P=0.047）, duration of disease （r=0.501, P=0.027）, 24 h urine protein excretion （r= 0.384, P=0.004）, Up/Uer （r=0.367, P=0.006）, TG （r=0.314, P=0.021）, and TC （r=0.444, P=0.001）, while controlling the serum lipid level, serum ANGPTL3 level was also correlated with 24 h urine protein excretion （r=0.348, P〈 0.001） and Up/Ucr （r=0.312, P〈 0.001）; Urine ANGPTIA/Cr was positively correlated with 24 h urine protein excretion （r=0.318, P=0.019）, Up/Uer （r=0.117, P=0.044）. （3） No difference of serum and urine ANGPTL3 and 4 levels were found among steroid-sensitive, steroid -resistant, steroid-dependent PNS groups, as well as between the frequency relapse or non-frequency relapse groups, while in steroid-dependent and frequency relapse NS children, serum ANGPTL3 level could reflect the curative effect on proteinuria. （4） In PNS children with similar degree of proteinuria and lipid levels, the serum ANGPTL3 levels varied in different pathological types. Conclusions Serum ANGPTL3 level may be an important indicator of PNS incidence, disease severities, pathological types and curative effect on proteinuria in PNS. Urine ANGPTIA level is correlated with proteinuria, which may have the clinical reference value in PNS.