Growth factors in the pathogenesis of renovascular complications of diabetes mellitus.

Abstract

We reviewed the evidence that links altered levels of circulating and intrarenal growth factors with the genesis of renal glomerular hypertrophy, microvascular disease and interstitial fibrosis as seen in diabetes mellitus. Insulin-like growth factor 1 (IGF-1) appears to be a hypertrophic factor in experimental renal disease, and is also known to be mitogenic for mesangial and vascular smooth muscle cells. However, an alteration in the balance of other factors, such as platelet-derived growth factor and angiotensin (Ang) II, could contribute to the growth disorder. Data from healthy animals suggest that the paracrine stimulation of interstitial fibroblasts by adjoining renal epithelial cells may contribute to the progressive interstitial fibrosis and microvascular occlusion found in diabetic nephropathy and other chronic renal diseases. The progressive fall in the glomerular filtration rate in patients with diabetic nephropathy may be partly explained by structural damage in the glomerulus subsequent to hyperfiltration and hypertrophy. However, interstitial disease is independently correlated with serum creatinine. There is no evidence to show whether growth factors contribute to the genesis of human diabetic nephropathy, and circulatory levels of IGF-1 and Ang II are not clearly correlated with renal disease. It is possible, but not proven, that intrarenal levels of growth factors may be particularly relevant to the pathogenesis of glomerular microvascular and interstitial disease.