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

• Published in: PloS one Vol. 11; no. 12; p. e0164936
• Main Authors: Uzu, Takashi, Araki, Shin-Ichi, Kashiwagi, Atsunori, Haneda, Masakazu, Koya, Daisuke, Yokoyama, Hiroki, Kida, Yasuo, Ikebuchi, Motoyoshi, Nakamura, Takaaki, Nishimura, Masataka, Takahara, Noriko, Obata, Toshiyuki, Omichi, Nobuyuki, Sakamoto, Katsuhiko, Shingu, Ryosuke, Taki, Hideki, Nagai, Yoshio, Tokuda, Hiroaki, Kitada, Munehiro, Misawa, Miwa, Nishiyama, Akira, Kobori, Hiroyuki, Maegawa, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.12.2016; Public Library of Science (PLoS)
• Subjects: Albumin; Albuminuria; Albuminuria - drug therapy; Aliskiren; Amides - therapeutic use; Angiotensin; Angiotensin II receptor blockers; Angiotensin Receptor Antagonists - therapeutic use; Angiotensinogen; Angiotensinogen - urine; Antihypertensive Agents - therapeutic use; Biology and Life Sciences; Blood; Blood pressure; Blood Pressure - drug effects; Comparative analysis; Creatinine; Creatinine - urine; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetic Nephropathies - pathology; Diabetics; Direct reduced iron; Dosage and administration; Drug therapy; End-stage renal disease; Endocrinology; Excretion; Fumarates - therapeutic use; Health aspects; Health risks; Hospitals; Humans; Hypertension; Hypertension - drug therapy; Hypertension - physiopathology; Inhibitors; Internal medicine; Kidney diseases; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - prevention & control; Medicine; Medicine and Health Sciences; Metabolism; Patients; Prospective Studies; Reduction; Renin; Renin - antagonists & inhibitors; Renin-Angiotensin System - drug effects; Risk factors; Science; Treatment Outcome; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164936

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.