Induction of AMPK Activity Corrects Early Pathophysiologic Alterations in the Subtotal Nephrectomy Model of Chronic Kidney Disease.

Induction of AMPK Activity Corrects Early Pathophysiologic Alterations in the Subtotal Nephrectomy Model of Chronic Kidney Disease. Am J Physiol Renal Physiol. 2013 Jul 3; Authors: Satriano J, Sharma K, Blantz RC, Deng A Abstract The rat kidney ablation and infarction (A/I) model of subtotal or 5/6(th) nephrectomy is the most commonly studied model of non-diabetic chronic kidney disease (CKD). The A/I kidney at one-week exhibits reductions in kidney function as determined by glomerular filtration rate (GFR), and diminished metabolic efficiency as determined by oxygen consumption per sodium transport (QO2/TNa). As renoprotective adenosine monophosphate-activated protein kinase (AMPK) activity is affected by metabolic changes and cellular stress, we evaluated AMPK activity in this model system. We show that these early pathophysiologic changes are accompanied by a paradoxical decrease in AMPK activity. Over time these kidney parameters progressively worsen with extensive kidney structural, functional, metabolic and fibrotic changes observed at four weeks post A/I. We show that induction of AMPK activity with either metformin or AICAR increases AMPK activity in this model, and also corrects kidney metabolic inefficiency, improves kidney function and ameliorates kidney fibrosis and structural alterations. We conclude that AMPK activity is reduced in the subtotal nephrectomy model of non-diabetic CKD; that altered regulation of AMPK is coincident w...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research