Beneficial effect on podocyte number in experimental diabetic nephropathy resulting from combined Atrasentan and RAAS inhibition therapy.

Beneficial effect on podocyte number in experimental diabetic nephropathy resulting from combined Atrasentan and RAAS inhibition therapy. Am J Physiol Renal Physiol. 2020 Apr 06;: Authors: Hudkins KL, Wietecha TA, Steegh F, Alpers CE Abstract Podocyte loss and proteinuria are both key features of human diabetic nephropathy. The leptin deficient BTBR mouse strain with the ob/ob mutation develops progressive weight gain, Type II diabetes and diabetic nephropathy that has many features of advanced human diabetic nephropathy, including increased mesangial matrix, mesangiolysis, podocyte loss, and proteinuria. Selective antagonism of the endothelin-1 receptor, ETAR, by atrasentan treatment in combination with RAAS inhibition with losartan has been shown to have the therapeutic benefit of lowering proteinuria in patients with diabetic nephropathy, but the underlying mechanism for this benefit is not well understood. Using a similar therapeutic approach in diabetic BTBR ob/ob mice, this treatment regimen significantly increased glomerular podocyte number compared with diabetic BTBR ob/ob controls, and suggested parietal epithelial cells were a source for podocyte restoration. Atrasentan treatment alone also increased podocyte number, but to a lesser degree. Mice treated with atrasentan demonstrated a reduction in proteinuria, matching the functional improvement reported in humans. This is a first demonstration that treatment with the highly...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research