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Angiotensin Receptor Antagonist Regresses Left Ventricular Hypertrophy Associated with Diabetic Nephropathy in Dialysis Patients

Kanno, Yoshihiko MD, PhD*; Kaneko, Keiko MD, PhD†; Kaneko, Masaharu MD†; Kotaki, Syuhei MD*; Mimura, Taku MD*; Takane, Hiroshi MD, PhD*; Suzuki, Hiromichi MD, PhD*

Journal of Cardiovascular Pharmacology:
Original Article
Abstract

Background: Left ventricular hypertrophy (LVH) is frequently found at the initiation of dialysis therapy for diabetic and hypertensive patients, and is highly predictive of future cardiac morbidity and mortality. Angiotensin type 1 receptor (AT1) antagonists may be able to regress LVH by mechanisms independent of their antihypertensive effects in diabetic patients. It is not known whether AT1 antagonists are able to reverse LVH in diabetic patients on dialysis therapy.

Method: Twenty-four type II diabetic patients with end-stage renal disease who had just entered into hemodialysis therapy, and were diagnosed as having LVH evaluated by echocardiography, were selected from 3 dialysis units staffed by the faculty of Saitama Medical School between 1998 and 2001. The study was carried out for 1 year. All patients were randomly assigned to 2 groups. One group received an AT 1 antagonist, losartan 100 mg daily 30 minutes after the cessation of dialysis therapy on dialysis days, or in the evening when dialysis therapy did not occur. The control group received placebo. LVH was evaluated by echocardiography before the start of administration of drugs, at 4 and 8 months, and again at 12 months after the start of drug therapy. A systolic blood pressure of less than 140 mm Hg was the target blood pressure in both groups.

Results: Using repeated measures analysis of variance, applied to those with 4 echocardiograms, there were progressive decreases over time in the left ventricular mass index (LVMi), posterior wall thickness, and intraventricular wall thickness in patients receiving losartan. The biggest changes in mass and the other parameters occurred between baseline and at month 6. Compared with these changes in the patients receiving losartan, left ventricular internal diameters and their derived parameters (e.g., ejection fraction) remained unchanged throughout the study. In spite of a similar reduction of bp in the patients receiving placebo, no significant changes in echocardiographic parameters were found in these patients.

Conclusion: An AT 1 antagonist, losartan, is beneficial for the regression of LVH in diabetic patients who started dialysis therapy under adequate blood pressure control.

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease (ESRD) in Japan 1 as well as the other countries. 2 In patients undergoing hemodialysis, left ventricular hypertrophy (LVH) has been identified as an independent risk factor for mortality. 3 Moreover, cumulative evidences have clearly demonstrated that arterial hypertension is a primary risk factor for LVH in the dialysis population. 4,5 Previously, strict blood pressure (bp) control in conjunction with antihypertensive therapy, including angiotensin converting enzyme (ACE) inhibitors, calcium antagonists, and beta blockers, was reported to induce regression of LVH. 6 Calcium antagonists are prescribed widely to patients with ESRD, principally for the treatment of hypertension. However, compared with the results obtained from the patients with ESRD, in patients with diabetes and hypertension, studies examining calcium antagonists use have reached mixed conclusions with regard to their effects on patient outcome. 7,8 In addition to these controversial data about the cardio- and renal-protective effects of calcium antagonists, recent evidence from large clinical trials such as Reduction of Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL), 9 and Losartan Intervention for Endpoint reduction (LIFE), 10 have demonstrated that the angiotensin type 1 receptor (AT1) antagonist is the best choice for cardio- and reno-protection in patients with hypertension and diabetes. In these studies, the AT1 antagonist was shown to have some specific actions beyond control in bp.

To date, no reports of the effects of AT1 antagonist on LVH of hypertensive patients on dialysis therapy are available. In the present study, we evaluated the effects of the AT1 antagonist on LVH of diabetic uremic patients who just started dialysis therapy under well-controlled bp.

Author Information

From the *Department of Nephrology, Saitama Medical School, †Irumadai Clinic, Saitama, Japan.

Received for publication April 8, 2003; accepted October 31, 2003.

Reprints: Hiromichi Suzuki, MD, PhD, Department of Nephrology, Saitama Medical School, Moroyama-machi, Iruma-gun, Saitama Prefecture, Japan. E-mail: iromichi@saitama-med.ac.jp

© 2004 Lippincott Williams & Wilkins, Inc.