MYOFIBROBLASTS AND ARTERIOLAR SCLEROSIS IN HUMAN DIABETIC NEPHROPATHY

y We examined the biopsy specimens of 62 patients with diabetic nephro pathy to establish whether the myofibroblast (MF) has a role in progre ssive interstitial fibrosis and to ascertain whether a relationship ex isted between MF activity and severity of arteriolosclerosis. MF were identified by morphology and cu smooth muscle actin (alpha SMA) immuno staining. Analysis of vascular injury was performed by counting the nu mber of interstitial arterioles after staining endothelial cells with von Willebrand factor (WVF) antibody. Arteriosclerosis was quantified by using a computer-aided image analyzer to measure the arteriolar wal l surface and total arteriolar surface area, and the ratio of wall to total surface area was expressed as the index of arteriosclerosis (IA) . Fractional area of interstitium (IFA), alpha SMA, and collagen III ( Cell III) were quantitated by point counting. Results were related to structural and functional parameters using rank correlation coefficien ts. There was a strong correlation between IFA and Cell III staining ( r = 0.83; P < 0.001). The alpha SMA staining correlated with IFA (r = 0.56; P < 0.001) and Cell III (r = 0.47; P < 0.001), and there were si gnificant correlations between alpha SMA and total urinary protein (r = 0.47; P < 0.001), renal function (plasma creatinine) at time of biop sy (r = 0.51; P < 0.001), and the percent change in plasma creatinine after 4 years (Delta Cr)(r = 0.37; P = 0.01). The IA correlated signif icantly with Cell III (r = 0.29; P = 0.02), glomerular filtration rate (GFR) (r = 0.39; P = 0.008), and creatinine (r = 0.33; P = 0.01), but no correlation was observed between alpha SMA and IA (r = 0.16; P = 0 .23) or IA and Delta Cr (r = -0.04; P = 0.8). Strong correlations coul d be shown between arteriolar density, IFA (r = 0.75; P < 0.001), alph a SMA (r = -0.36; P = 0.034), and Cell III (r = -0.66; P < 0.0001). Th e MF appears to have a significant role in the progression of diabetic nephropathy. Ischemia secondary to arteriosclerosis may contribute to interstitial fibrosis through fibroblast modulation into MF. (C) 1997 by the National Kidney Foundation, Inc.