The Detection Of Urinary TGF-betal,IL-6 And Col-Ⅳ And Their Significance In IgA Nephropathy

Objective The aim of study was to demonstrate if levels of urinary Transforming growth factor-betal (TGF-betal) , interleukin-6 (IL-6) and tpye IV Collagen (Col -IV) correlated with expression of TGF-betal and Col-IV and histological damage in renal biopsies in IgA nephropathy (IgAN).Material sand Methods Urinary TGF-betaK IL-6 and Col-IV levels were determined by ELISA and the expression of TGF-betal and Col-IV were examined by iramunohistochemistry from renal biopsies in 110 patients with IgA nephropathy. 76 cases healthy subjects served as control. In addition, density of glomerular matrix membrane and quantity of cell in glomeruli were measured with CMIAS image analysis system by computer. Global sclerosis, cellular crescents, fiber or fibrocellular crescents were measured with Memphis scope. Tubulointerstitial lesions were examined with semi-quantitative grades (including O-III grades).Results Compared to normal control, there was a significant increase of urinary TGF-betaK IL-6 and Col-lV levels in patients with IgAN (p<0. 01). There were also significantly positive correlation between the levels of urinary TGF-betaK Col-IV and density of glomerular matrix membrane ., interstitial fibrosis(p<0. 01). It had negative correlation with levels of, urinary TGF-betaK Col-IV and quantity of cell in glomeruli (p<0. 05). Theurinary IL-6 level positively correlated with density of glomerular matrix membrane, global sclerosis, fiber or fibrocellular crescents and interstitial fibrosis (p<0. 05). According to the degree of density of glomerular matrix membrane and interstitial fibrosis, urinary Col-IV level had better correlation than urinary TGF-betal and IL-6 levels.In IgAN, Col-IV showed increased expression in diseased renal tissue whereas the site of expression of TGF-betal was mainly localized within the cytoplasm of tubular epithelial cells. Interstial expressionwas also present but glomerular TGF-betal expression was found only in patients with heavy mesangial proliferation. There was a significant correlation between glomerular positivity for Col-IV and severity of histological damage. There was also a significant correlation between positivity for TGF-betal and Col-IV in the tubular epithelial and interstitial lesions. In contrast, there was no ralationship between glomerular positivity for TGF-betal and severity of histological damage.The urinary TGF-betal level paralleled tubular TGF-betal expression. There was positive correlation between urinary Col-IV level and expression of Col- IV in diseased glomeruli and tubulointerstitial areas.Conclusion Our data show that: (1) renal Col-IV expression and tubulointerstitial TGF-betal expression are strictly correlated to the degree of histological damage;and (2) Urinary TGF-betal, IL-6 and Col-IV levels can reflect early histological damage in IgA nephropathy. Urinary Col-IV level might be a valuable prognostic marker for the progression of the renal damage in IgA nephropathy.