Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial

Takashi Uzu, Shin-Ichi Araki, Atsunori Kashiwagi, Masakazu Haneda, Daisuke Koya, Hiroki Yokoyama, Yasuo Kida, Motoyoshi Ikebuchi, Takaaki Nakamura, Masataka Nishimura, Noriko Takahara, Toshiyuki Obata, Nobuyuki Omichi, Katsuhiko Sakamoto, Ryosuke Shingu, Hideki Taki, Yoshio Nagai, Hiroaki Tokuda, Munehiro Kitada, Miwa Misawa, Akira Nishiyama, Hiroyuki Kobori, Hiroshi Maegawa
PloS One 2016, 11 (12): e0164936

BACKGROUND: In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity.

METHODS: We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to <30 mg/g of albumin-to-creatinine ratio) or microalbuminuria (30 to <300 mg/g) to the DRI group or ARB group (any ARB) with a target blood pressure of <130/80 mmHg. The primary endpoint was a reduction in albuminuria.

RESULTS: Twelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients.

CONCLUSION: DRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen.

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