title: Selection of the dose of angiotensin converting enzyme inhibitor for patients with diabetic nephropathy depends on the presence or absence of left ventricular hypertrophy.
abstract: The coexistence of hypertension increases cardiovascular risks and the rate of deterioration of renal function for diabetic patients. For patients with left ventricular hypertrophy (LVH), the use of an angiotensin converting enzyme (ACE) inhibitor is known to be effective and well tolerated and to be protective against chronic renal insufficiency (CRI). However, serious adverse reactions to ACE inhibitors, such as the rapid deterioration of renal function, have been reported, making physicians hesitant to use these agents. To resolve this dilemma, we compared changes in renal function and left ventricular function and the safety and effectiveness of benazepril, an ACE inhibitor, in patients with diabetic nephropathy, with or without LVH. The age, sex, duration of diabetes, levels of blood pressure and blood glucose and rates of creatinine clearance (CrCl) were compared between 36 diabetic patients with LVH and 36 matched diabetic patients without LVH. The rates of CrCl in all patients were between 14 and 35 ml/min, and all patients received an ACE inhibitor before enrollment. The group comprised 43 men and 29 women, with a mean age of 56 +/- 4 years. These patients were divided into three groups, each of which was subdivided into a group with and a group without LVH. Group I (without LVH) or I-L (with LVH) received a half dose of benazepril (2.5 mg daily), Group II (without LVH) or II-L (with LVH) received a normal daily dose of 5 mg benazepril, and Group III (without LVH) or III-L (with LVH) discontinued the administration of the ACE inhibitor. The follow-up period was 1 year and, during the study, blood pressure was maintained at less than 140/90 mmHg. If the blood pressure control was not satisfactory, benidipine, a calcium antagonist, and/or furosemide, a loop diuretic, and/or guanabenz, a central acting antihypertensive agent, were administered. In the diabetic patients with LVH, the administration of a normal dose of benazepril inhibited the decline of renal function and cardiac function (CrCl: 24.2 +/- 1.5 to 22.0 +/- 2.5 ml/min; EF (ejection fraction): 56 +/- 3 to 54 +/- 6%) compared to the other two groups. In patients without LVH, a half dose of benazepril preserved renal function (23.4 +/- 2.6 to 22.0 +/- 3.1 ml/min; EF: 54 +/- 3 to 56 +/- 3%). Discontinuation of the administration of ACE inhibitor led to the further progression of renal dysfunction and decreases in EF in patients with or without LVH. Our results provide some indications for the use of ACE inhibitors in diabetic patients when renal dysfunction and/or cardiac hypertrophy are present.
authors.affiliation: Department of Nephrology, Saitama Medical School, Saitama, Japan. iromichi@saitama-med.ac.jp
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kanno
authors.forename: Naofumi
authors.initials: N
authors.lastname: Ikeda
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Nakamoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okada
authors.forename: Souichi
authors.initials: S
authors.lastname: Sugahara
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm; D003401:Creatine / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D011188:Potassium / Q000097:blood; D011507:Proteinuria / Q000188:drug therapy / Q000652:urine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D006454:Hemoglobins; D003401:Creatine; D011188:Potassium; C044946:benazepril