PLoS ONE (Jan 2016)

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,
  • Shiga Committee for Preventing Diabetic Nephropathy

DOI
https://doi.org/10.1371/journal.pone.0164936
Journal volume & issue
Vol. 11, no. 12
p. e0164936

Abstract

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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.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.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.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.