SP417EFFECT OF DAPAGLIFLOZIN ON ALBUMINURIA AND THE RENIN-ANGIOTENSIN SYSTEM WHEN ADDED TO RENIN-ANGIOTENSIN BLOCKADE IN PATIENTS WITH TYPE 2 DIABETES AND NEPHROPATHY

Abstract

INTRODUCTION AND AIMS: The Objective is to evaluate the effect of dapagliflozin treatment on albuminuria, measured GFR, 24h blood pressure and hormone levels of the renin-angiotensin system (RAS) when added to standard care including RAS blocking treatment in patients with type 2 diabetes (T2D). METHODS: Double-masked randomized placebo-controlled crossover trial of 12 weeks treatment with dapagliflozin 10mg or matching placebo. All patients were treated with RAS blocking treatment. Included patients (n=40) had T2D, albuminuria at baseline. At the end of the treatment periods 3 consecutive morning spot urines were collected as well as 24h blood pressure measurement and 51Cr-EDTA performed.Values at the end of treatment periods (placebo vs. dapagliflozin) were compared using mixed model analysis. RESULTS: Baseline geometric mean urinary albumin creatinine ratio (UACR) was 147 (IQR 75-289) mg/g, mean eGFR 85 ml/min/1.72 m2 (SD619.7). Baseline HbA1c was 73 mmol/mol (SD615) and 24h blood pressure 148/82 mmHg (SD612.5/7.7). After 12 weeks treatment UACR was reduced 36% (95% CI 16-56%) during treatment with dapagliflozin vs. placebo (p<0.01), GFR decreased 10.9 (5-16) ml/min (p<0.01), HbA1c was reduced 7.4 (5-10) mmol/mol (p<0.01) and 24h blood pressure 4.8/2.7 mmHg (p=0.023/0.031). Plasma renin concentration increased 37% (9-66%), plasma renin activity increased 41% (7-74%), angiotensin II increased 37% (1-73%) (all statistically significant) whereas plasma aldosterone was unchanged. CONCLUSIONS: When added to standard RAS blocking treatment dapagliflozin 10 mg vs. placebo once daily was associated with a clinically significant reduction in albuminuria, 24h blood pressure and GFR in patients with T2D and albuminuria. A concomitant increase in RAS hormones was observed, potentially reflecting an increased natriuresis.