Abstract P228: Mineralocorticoid Receptor Antagonist And Lipophilic Statin Reduce Urinary Kidney Injury Marker 1 (Kim-1) In Female Rats Receiving L-NAME And Angiotensin II

Abstract

Statins have beneficial cardiovascular effects some of which appear to be cholesterol-independent and the mechanisms for these latter effects are still unclear. Urinary kidney injury molecule-1 (Kim-1) is a sensitive biomarker of acute renal injury and in clinical studies predicts cardiovascular disease. Aldosterone causes both cardiac and renal injury and a few studies suggest that aldosterone is associated with increased Kim-1. Therefore, in this study we used the N omega-nitro-L-arginine methyl ester (L-NAME)/Angiotensin II (AngII) model of cardiorenal injury to determine whether urinary Kim-1 correlates with the degree of cardiac injury/stroke and whether blockade of the mineralocorticoid receptor prevents increases in urinary Kim-1. Further, since our group reported previously that lipophilic statins, but not hydrophilic statins reduce aldosterone levels, we also asked whether administration of either a lipophilic or a hydrophilic statin affects Kim-1 levels. To test the hypothesis, 8-10 week-old, female Wistar rats consuming liberal salt diet (1.6% Na + ) were randomized to the following conditions for 14 days: control; L-NAME (0.2 mg/ml in drinking water)/AngII (225ug/kg/day for days 12-14 only); L-NAME/AngII + eplerenone (100 mg/kg/day p.o.); L-NAME/Ang II + pravastatin (hydrophilic statin-20 mg/kg/day p.o.); L-NAME/Ang II + simvastatin (lipophilic statin-20 mg/kg/day p.o.) groups. Groups treated with L-NAME/AngII had significantly higher blood pressure, urine aldosterone and plasma aldosterone levels compared to control. L-NAME/AngII treatment increased cardiac injury/stroke composite score, including cardiac histopathology evaluation and stroke status, and 24 hour-urinary Kim-1 compared to control. Eplerenone reduced cardiac injury/stroke composite score (p=0.04) and both eplerenone and simvastatin reduced urinary Kim-1 (p=0.0046, p=0.031, respectively). Pravastatin had no effect on these damage markers. Urinary Kim-1 correlated with cardiac injury/stroke composite score (p<0.0001, spearman ranked correlation=0.67). In conclusion, in a rat model of L-NAME/AngII induced cardiovascular injury, urinary Kim-1 predicts cardiac/stroke injury; eplerenone and simvastatin reduced urinary Kim-1.