急性肾损伤标志物在钙调神经蛋白抑制剂治疗难治性肾病综合征中的意义  

Significance of acute kidney injury biomarkers in the treatment of refractory nephrotic syndrome with calci- neurin inhibitors

作　　者：陈咏琦[1,2] 朱艳[1,2] 郝胜[1,2] 王平[1,2] 朱光华[1,2] 黄文彦[1,2] 吴滢[1,2] 

机构地区：[1]上海交通大学附属儿童医院,200062 [2]上海市儿童医院肾脏风湿科

出　　处：《中华实用儿科临床杂志》2017年第17期1300-1304,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：教育部留学凹国人员肩动基金（20150909-5）

摘　　要：目的探讨急性肾损伤标志物在评估儿童难治性肾病综合征治疗中钙调神经蛋白抑制剂（CNI）相关肾毒性的检测意义。方法选择2014年3月至2015年12月在上海市儿童医院肾眦风湿科住院的儿童肾病综合征患儿共92例，男59例，女33例；年龄（5．67±3．65）岁。其中单纯激素治疗的患儿66例为对照组，男44例，女22例；年龄（4．97±3．52）岁。激素联合环孢素（CsA）／他克莫司（FK506）治疗的患儿26例为观察组，男15例，女11例；年龄（6．59±3．95）岁。以药物治疗前（0d）和治疗极早期（3d）、早期（1个月）、中期（3个月）和后期（6个月）为不同的观察时间点，比较血、尿中性粒细胞明胶酶相关性脂质运载蛋白（NGAL）、肾损伤分子-1（KIM-1）、纤维连接蛋白（FN）及肿瘤坏死因子α（TNF—α）4个生物学标志物在不同时间点的水平变化，并与传统检验指标尿视黄醇结合蛋白（RBP）和N-乙酰-β—D葡萄糖酐酶（NAG）对比观察其变化趋势。结果观察组血清NGAL（sNGAL）水平在CNI治疗6个月时间点明显高于对照组，差异有统计学意义[（138．00±32．49）μg/L比（46．54±11．41）μg/L，t=2．115，P〈0．05]；观察组尿TNF—α（uTNF-α）水平在CNI治疗6个月时间点明显高于对照组，差异有统计学意义[（2．35±0．78）pg／μmol比（0．75±0．36）pg/μmol，t=1．840，P〈0．05]；观察组尿液KIM-1（uKIM—1）在CNI治疗3个月时间点明显低于对照组，筹异有统计学意义[（0．15±0．03）ng／μmol比（0．33±0．07）ng／μmol，t=-2．077，P〈0．05]；观察组尿液NGAL（uNGAL）在CNI治疗3个月时间点明显低于对照组，差异有统计学意义[（0．09±0．03）ng／μmol比（0．23±0．04）ng/μmol，t=-2．959，P〈0．05]；血清TNF—α（sTNF—α）、尿液FN（uFN）、尿液RBP（uRBP）和尿液NAG（uNAG）水平任CNI治疗前后变化差异均无统计�Objective To investigate the significance of acute kidney injury biomarkers with calcineurin inhibitors （CNI） related nephrotoxieity in the treatment of refractory nephritic syndrome. Methods Ninety - two patients were included with 59 males and 33 females with average age of （5.67 ± 3.65 ） years old, who were diagnosed with ne- phrotic syndrome at Shanghai Children＇s Hospital from March 2014 to December 2015.66 patients including 44 males and 22 females with mean age of （4.97 ±3.52） were treated by steroid as the control group and 26 patients including 15 males and 11 females with mean age of （6.59 ±3.95） were treated by steroid combined with CsA and FK506 as the observation group. The blood,urine samples were collected before drug treatment （0 d） and very early stage of treat- ment （3 d） ,early stage （ 1 month） ,middle and late stage （3 months and 6 months） as the difterent observation time points. The change level of neutrophil gelatinase associated lipocalin（ NGAL）, kidney injury molecular - 1 （KIM - 1 ）, fibronectin（FN） and tumor necrosis factor- alpha（TNF -α） in serum and urine were detected at different time points to compare with biomarkers such as retinol - binding protein（ RBP）, N - acetyl - β - D - glucosamccharase（NAG） in urine. Results The serum NGAL（sNAGL） level was more obvious ＇after 6 months of CNI treatment in the observation group than in the control group [ （ 138.00 ± 32.49 ） μg/L vs. （46.54 ± 11.41 ） μg/L, t = 2. 115, P 〈 0.051 ; the level of urine TNF - α （ uTNF - α） was higher obviously after 6 months of CNI treatment in the observation group than in the control group with significant differences [ （ 2.35 ± 0.78 ） pg/p, mol vs. （ 0. 75 ± 0.36 ） pg/μmol, t = 1. 840, P 〈 0. 05 ] ; the level of urine KIM - 1 （ uKIM - 1 ） was lower in the observation group than the control group after 3 months treatment of the CNI [ （0.15 ± 0.03 ） ng/μmol vs. （0.33 ± 0.07 ） ng/μmol, t = - 2. 077

关 键 词：钙调神经蛋白抑制剂 肾损伤 中性粒细胞明胶酶相关性脂质运载堡白 肾损伤分子-1 纤维连 接蛋白 肿瘤坏死因子Α 

分 类 号：R692[医药卫生—泌尿科学]