尿Ⅳ型胶原对早期诊断慢性肾脏病进展的临床应用价值

The Clinical Value Of Urinary Type Ⅳ Collagen in Predicting Progress of Chronic Kidney Disease

目的通过检测慢性肾脏病(CKD)患者尿Ⅳ型胶原(Col-Ⅳ)水平与肾组织Col-Ⅳ表达和肾脏病理之间的关系,寻找一种能早期反映CKD进展的非创伤性临床检测指标。方法选取98例接受肾穿刺检查的CKD患者为研究对象,76例健康人为对照组,用ELISA法测定患者血、尿Col-Ⅳ浓度;免疫组化法检测肾组织Col-Ⅳ表达;应用计算机病理图像分析系统对肾病理进行半定量分析,观察尿Col-Ⅳ水平与肾组织Col-Ⅳ表达及肾病理损伤的关系;并与尿蛋白排泄和肾小球滤过率(eG-FR)同步对比分析。结果肾病患者尿Col-Ⅳ浓度较健康人明显增高,而血中浓度无差异;在硬化的小球和小管间质均有Col-Ⅳ表达,并随病变加重表达增强,尿Col-Ⅳ浓度与肾组织Col-Ⅳ表达水平呈正相关,也与肾小球基质基膜面密度、小管间质损害显著正相关;尿Col-Ⅳ在轻度肾硬化时已升高,其改变明显早于eGFR异常,且与尿蛋白的排泄不相关。结论尿Col-Ⅳ水平反映了肾组织中的Col-Ⅳ表达水平及肾硬化的程度,可以作为CKD患者病情进展的早期临床检测指标。

Objective To determine an early and noninvasive predictor of chronic kidney diseaase（CKD） ,by detecting the correlation between the urinary Col - Ⅳ concentration,the renal tissue and renal lesions in patients with CKD Col - Ⅳ expression. Methods 98 CKD patients proved by renal biopsy were selected and 76 healthy people were enrolled as control. Urinary and serum Col - Ⅳ concentration were examined by enzyme -linked immunosorbent assay（ ELISA）. Renal Col - Ⅳ expression was detected by immunohistochemistry. Renal injury grade was semiquantitative by CMIAS image analysis system. The association between urinary Col - Ⅳ level and renal Col - Ⅳ expression, as well as renal lesion was analyzed,meanwhile the proteinuria and glomerular filtration rate（GFR） were analysed simultaneously. Results Urinary Col - Ⅳ level in patients with CKD was significantly higher than that in control,however, there was no difference in blood Col - Ⅳ level. Expression of Col - Ⅳ could be found in the sclerosing glomeruli and tubulointerstitial tissue, and Col - Ⅳ expression degree was consistent with lesion degree. Urinary Col - Ⅳ level was correlated positively with renal Col - Ⅳ expression, as well as with density of glomerular basement membrane and interstitial damage. Elevated urinary Col - Ⅳ concentration was observed in patients with mild renal sclerosis prior to the change of GFR. No correlation between urinary Col - Ⅳ concentration and proteinuria was observed. Conclusions These results suggested urinary Col - Ⅳ concentration reflected renal Col - Ⅳ expression and renal sclerosis, and could predict the progression of CKD.