尿中性肽链内切酶的检测及其在诊断肾小管损伤中意义

Measurement of urinary neutral endopeptidase and its significance in diagnosing renal tubular injury

目的 建立尿中性肽链内切酶(NEP)浓度的检测方法并结合临床,探讨它与肾小管损伤的关系。方法 将研究组分为对照组(n=100),单纯肾小球疾病组(n=31)、急性肾小管损伤组(n=44)、慢性肾小管损伤组(n=48)、马兜铃酸肾病组(n=13)、慢性肾功能衰竭(CRF)组(n=13)。收集各组患者晨尿,用荧光光谱分析法测得尿NEP的浓度,并用相应尿肌酐值予以标化。同时检测各组患者的尿微量蛋白。结果 急性肾小管损伤组尿NEP明显高于正常对照组(P=0.0001),慢性肾小管损伤组、马兜铃酸肾病组、CRF组尿NEP均明显低于正常对照组(P均<0.01),而单纯肾小球疾病组尿NEP与正常对照组无差异(P=0.142 5)。在急性组尿NEP与尿NAG成正相关,与其他几种尿微量蛋白间无相关性。在其他几组内,尿NEP与Ccr成正相关,与尿微量蛋白成负相关。在肾小球疾病组内尿NEP与尿微量蛋白无明显相关性。结论 本研究在国内率先建立了尿NEP的检测方法,并用于临床研究。对尿中NEP的检测,提供了一种快速、非损伤性测量手段,籍此帮助判断近端肾小管损伤,结合其他小管损伤的指标可以帮助判断病程。

Objective To explore the relationship between urinary neutral endopeptidase and renal tubular injury. Methods All the persons in our study were divided into six groups which included control group( n = 100),acute tubular injury group(n=44),chronic tubular injury group(n=48),glomerular diseases group ( n = 31),aristolochic acid nephropathy group ( n=13),chronic renal failure group ( n=13). Urinary neutral endopeptidase enzymatic activity was spectrofluorimetrically measured,using a synthetic peptidic substrate. At the same time,measurements of urinary microproteins were performed as indicators of tubular dysfunction. Results The NEP value of control group was 68. 41μg/mmol Cr. The NEP value of acute tubular injury group( 196. 36μg/mmol Cr) was higher than normal control ( P = 0. 000 1),while the values of chronic tubular injury group(31.64 μg/mmol Cr),aristolochic acid nephropathy group(32. 78 μg/mmol Cr) and chronic renal failure group( 19. 40μg/mmol Cr) were much lower than normal control( P < 0. 01). The NEP value of glomerular diseases group (75. 49μg/mmol Cr) had no significant difference from that of normal control(P = 0. 142 5) . In acute tubular injury group,urinary NEP had positive relationship with urinary NAG( r = 0. 315 8,P = 0.0368) . In chronic tubular injury group,aristolochic acid nephropathy group and chronic renal failure group,urinary NEP was positively correlated with individual creatinine clearance values and negatively correlated with urinary microproteins levels. The urinary NEP had no significant relationship with urinary IgG and TRU. Conclusions In acute tubular injury patients, their urinary NEP increases obviously but in chronic tubular injury patients,the urinary NEP decreases significantly. As a result,the measurement of urinary NEP will be helpful in diagnosing tubular injury.