Albumin contributes to kidney disease progression in Alport syndrome.

Albumin contributes to kidney disease progression in Alport syndrome. Am J Physiol Renal Physiol. 2016 May 4;:ajprenal.00456.2015 Authors: Jarad G, Knutsen RH, Mecham RP, Miner JH Abstract Alport syndrome is a familial kidney disease caused by defects in the collagen IV network of the glomerular basement membrane. The lack of collagen α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role albumin plays in progression of disease in Alport syndrome, we generated albumin knockout (Alb-/-) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb+/- mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to Col4a3-/- mice, which are a model for human Alport syndrome. The lack of circulating and filtered albumin in Col4a3-/-;Alb-/- mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3-/-;Alb+/+ and Col4a3-/-;Alb+/- mice, despite similar blood pressures and serum triglyceride levels. Further investigations sho...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research