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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 explore a non-invasive clinical detection index that can reflect the progress of CKD early by detecting the relationship between urinary type Ⅳ collagen (Col-Ⅳ) and the expression of Col-Ⅳ and renal pathology in patients with chronic kidney disease (CKD) . Methods Ninety-eight CKD patients who underwent renal biopsy were selected as experimental group and 76 healthy individuals as control group. Serum and urinary Col-Ⅳ concentrations were measured by ELISA. The expression of Col-Ⅳ in renal tissues was detected by immunohistochemistry. The semi-quantitative analysis of renal pathology was performed by image analysis system to observe the relationship between urinary Col-Ⅳ level and the expression of Col-IV in nephridial tissue and the pathological damage of nephropathy, and to compare with the urinary protein excretion and glomerular filtration rate (eG-FR) analysis. Results Urine Col-Ⅳ concentration in patients with nephropathy was significantly higher than that in healthy people, but no difference in blood concentration. Col-IV expression was found in sclerotic globules and tubulointerstitium, The expression of Col-Ⅳ in renal tissue was positively correlated with glomerular matrix density and tubulointerstitial damage. Urinary Col-Ⅳ was increased in mild glomerulosclerosis, which was significantly earlier than eGFR , And is not associated with urinary protein excretion. Conclusion Urinary Col-Ⅳ level reflects the expression of Col-Ⅳ in renal tissue and the degree of nephrosclerosis, which can be used as an early clinical detection index for the progression of CKD patients.