Renoprotective Effects of the Direct Renin Inhibitor Aliskiren, Irbesartan and the Combination in Patients With Type 2 Diabetes, Hypertension and Albuminuria
Abstract Number: 6-LB
Authors: FREDERIK PERSSON, PETER ROSSING, HENRIK REINHARD, TINA JUHL, COEN D. STEHOUWER, CASPER SCHALKWIJK, A.H. JAN DANSER, FRANS BOOMSMA, ERIK FRANDSEN, HANS-ARMIN DIETERICH, MARGARET F. PRESCOTT, WILLIAM P. DOLE, HANS-HENRIK PARVING, Gentofte, Denmark, Maastricht, Netherlands, Rotterdam, Netherlands, Glostrup, Denmark, Basel, Switzerland, East Hanover, NJ, Copenhagen, Denmark, Aarhus, Denmark
Institutions: East Hanover, NJ
Results: Aliskiren (ALI) and the angiotensin receptor blocker irbesartan (IRB) have antiproteinuric and antihypertensive effects in patients with type 2 diabetes. We compared the antiproteinuric effects of ALI, IRB and the combination (ALI+IRB) in a double-blind, randomized, cross-over trial. After 1 month washout, 24 patients with type 2 diabetes, hypertension and albuminuria (>30 mg/day) were randomized to four 2-month treatment periods with once-daily placebo, ALI 300 mg, IRB 300 mg or ALI+IRB. Patients received furosemide to control sodium retention. Primary endpoint was change in urinary albumin excretion rate (UAER). Secondary measures included change in blood pressure (BP) and renin system biomarkers. Results are geometric mean change vs placebo.
ALI reduced UAER (baseline 258 mg/day) by 48% (95% CI 27, 62), not different from IRB (58% reduction [42, 70]; both p<0.001). ALI+IRB reduced UAER by 71% (59, 79), significantly more than either monotherapy (p≤0.028). Seated office BP (baseline 135/78 mmHg) was reduced 7/4 mmHg by ALI, 6/4 mmHg by IRB and 12/8 mmHg by ALI+IRB, all significant (p<0.05) except IRB for diastolic BP. GFR (baseline 89 mL/min/1.73m2) was reduced 4.6 (-8.8, -0.3) mL/min by ALI, 8.0 (-12.3, -3.6) mL/min by IRB and 11.7 (-15.9, -7.4) mL/min by ALI+IRB. ALI+IRB increased plasma potassium by 0.2 mmol/L (p=0.036). ALI reduced high sensitivity plasma renin activity (hsPRA), angiotensin (Ang) I and Ang II by 87%, 75% and 52%; IRB increased these biomarkers by 321%, 207% and 237%, respectively (all p<0.001). Although ALI+IRB caused a 12-fold increase in plasma renin concentration (PRC), the stimulatory effect of IRB on hsPRA, Ang I and Ang II was inhibited by ALI. Active treatment-related reductions in UAER correlated significantly with increases in PRC (r=-0.339, p=0.005). In conclusion, ALI and IRB each reduced albuminuria to the same degree, with different effects on renin system biomarkers. ALI+IRB provided larger reductions in albuminuria that correlated with more complete intra-renal renin system blockade (increases in PRC), suggesting the potential for improved renoprotection.