Vleming L J, Baelde J J, Westendorp R G, Daha M R, van Es L A, Bruijn J A
Department of Nephrology, University Hospital Leiden, The Netherlands.
Clin Nephrol. 1995 Oct;44(4):211-9.
The degree of impairment of renal function in patients with chronic renal failure correlates closely with the extent of fibrosis in the tubulointerstitium, i.e. of interstitial extracellular matrix (ECM) accumulation. The composition of this pathological extracellular matrix and the relation between the ECM composition on the one hand and the severity of histological changes and renal function on the other has not been investigated. This prompted us to perform the present study. The severity of histological abnormalities and the composition of the interstitial ECM were assessed using a semiquantitative scoring technique in 57 biopsies from patients with kidney disease of diverse etiology and variable degrees of renal failure and were contrasted with the results of 9 control biopsies. Tissue sections were stained with an indirect immunoperoxidase technique using antibodies against collagen I, III, IV, V, VI, laminin, fibronectin, decorin and heparansulphate proteoglycan core protein (HSPG). Collagen IV, laminin and HSPG were virtually absent from the interstitium in controls. These components were more widely distributed in patients and the extent of their deposition correlated with the severity of interstitial histological abnormalities. In patients with severe interstitial damage the deposition became diffuse. Collagen type I and III were already diffusely distributed in the interstitium of controls and did not increase significantly as interstitial damage became more severe. However, the extent of collagen III staining in patients was significantly higher than in controls. Decorin staining showed a patchy distribution both in patients and controls. The overall distribution was significantly increased in patients. The extent of the deposition of both collagen V and VI was significantly increased in patients when compared with controls. Only the distribution of collagen V correlated with the severity of histological abnormalities. Our findings suggest that an increased interstitial deposition of extracellular matrix substances which are generally regarded as basement membrane components contributes more to the development of interstitial fibrosis and renal failure than the deposition of the fiber forming interstitial collagens type I and III, which are prominent in controls and in patients irrespective of the severity of histological abnormalities. Decorin staining was significantly enhanced in patients and was found to be the best predictor both of the severity of interstitial fibrosis and of renal failure. This could mean that decorin is important in human renal pathology. Collagen V and VI staining was significantly increased in patients when compared with controls. To our knowledge this is the first study in which this is demonstrated.
慢性肾衰竭患者的肾功能损害程度与肾小管间质纤维化程度密切相关，即与间质细胞外基质（ECM）积聚程度密切相关。这种病理性细胞外基质的组成以及一方面ECM组成与另一方面组织学变化严重程度和肾功能之间的关系尚未得到研究。这促使我们开展本研究。我们采用半定量评分技术，对57例病因多样、肾衰竭程度各异的肾病患者的肾活检组织进行评估，测定组织学异常的严重程度和间质ECM的组成，并与9例对照肾活检结果进行对比。组织切片采用间接免疫过氧化物酶技术，用抗I、III、IV、V、VI型胶原、层粘连蛋白、纤连蛋白、核心蛋白聚糖和硫酸乙酰肝素蛋白聚糖核心蛋白（HSPG）的抗体进行染色。对照组织的间质中几乎不存在IV型胶原、层粘连蛋白和HSPG。这些成分在患者中分布更广泛，其沉积程度与间质组织学异常的严重程度相关。在严重间质损伤的患者中，沉积变得弥漫性。I型和III型胶原在对照组织的间质中已呈弥漫性分布，随着间质损伤加重，其含量无显著增加。然而，患者中III型胶原染色程度显著高于对照。核心蛋白聚糖染色在患者和对照中均呈斑片状分布。患者中的总体分布显著增加。与对照相比，患者中V型和VI型胶原的沉积程度均显著增加。只有V型胶原的分布与组织学异常的严重程度相关。我们的研究结果表明，一般被视为基底膜成分的细胞外基质物质在间质中的沉积增加，比在对照组织和患者中均很突出的形成纤维的I型和III型间质胶原的沉积，对间质纤维化和肾衰竭的发展贡献更大。患者中核心蛋白聚糖染色显著增强，并且被发现是间质纤维化严重程度和肾衰竭的最佳预测指标。这可能意味着核心蛋白聚糖在人类肾脏病理学中很重要。与对照相比，患者中V型和VI型胶原染色显著增加。据我们所知，这是首次证明这一点的研究。
