The renin angiotensin system and nephrin in diabetic nephropathy

The renin-angiotensin system (RAS) plays a pivotal role in the progression of renal diseases including diabetic nephropathy. A prominent effect of agents which interrupt the RAS in the diabetic kidney is the reduction or stabilisation of albuminuria. Recent slit pore proteins such as nephrin have been identified which localise to the slit diaphragm of the glomerular epithelial cell and are considered to play a role in the transglomerular passage of albumin. Recent studies by our and other groups have detected nephrin deficiency in the diabetic kidney in association with a reduction in slit pore density. In a series of studies by our group in an animal model of diabetes and hypertension (diabetic SHR) we have detected a transient increase in nephrin gene expression in diabetic rats followed by a progressive decline in nephrin gene expression in association with increasing albuminuria in diabetic SHR. This increase in albuminuria is prevented by administration of All receptor antagonists in association with prevention of glomerular nephrin gene and protein depletion. Similar effects of All receptor blockers in restoring renal nephrin content have been observed in non-diabetic models of renal disease. It remains to be determined if these changes in nephrin are causative or purely a manifestation of diabetic renal injury.