PS 08-11 THE EFFECT OF MINERALOCORTICOID ANTAGONIST ON RENAL INSULIN RESISTANCE AND THE PROGRESSION OF RENAL FAILURE IN NON-DIABETIC CKD PATIENTS

Abstract

Objective: Insulin resistance (IR) is evident in Chronic Kidney Disease (CKD ) even in non-diabetic patient, although the clinical relevances remain to be determined. We reported that aldosterone increase in CKD is contributed to IR in CKD and MR antagonist, spironolactone ameliorated IR in CKD in three months treatment. We follow our CKD cohort for five years and explored the relevance of IR in the progression of CKD. We also performed procebo-controlled clinical trial using mineralocorticoid receptor antagonist eplerenone and examined its effects on the progression of CKD. Design and Method: Between 2007 and 2008, consecutive 197 patients with CKD were enrolled and followed these patients for five years. Risk factors for the progression of CKD evaluated by the rate of eGFR decline was determined by multiple regression analysis. We recruited the patients with hyperaldosterone and IR patients (N = 48) and treated them with eprelenone (N = 22) and placebo (N = 26) for three years and evaluated its effect on eGFR decline. Results: In CKD patients, HOMA-IR levels were negatively associated with eGFR levels. Plasma aldosterone concentration was determined as an independent risk factor for HOMA-IR levels. After three years follow-up, baseline HOMA-IR levels was significantly associated with eGFR decline and selected as a independent risk factor. We classified quartile groups depending on the baseline HOMA-IR levels and found out the 3rd and 4th quartile groups were significantly higher decline in eGFR. Finally, eplereneone ameliorated eGFR decline of non-diabetic CKD patients with high HOMA-IR and high plasm aldosterone levels(eplerenone; eGFR 51.0 ± 3.7→50.4 ± 3.4 ml/min, placebo; eGFR 55.6 ± 5.1→53.1 ± 4.7 ml/min). Conclusions: IR is a risk factor of the progression of CKD and mineralocorticoid receptor antagonist will provide a novel strategy against the progression of CKD through the amelioration of IR.