Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Enalapril over 5 years reduced albuminuria and deterioration in renal function in normotensive patients with type 2 diabetes mellitus and microalbuminuria

ACP J Club. 1993 July-Aug;119:6. doi:10.7326/ACPJC-1993-119-1-006


Source Citation

Ravid M, Savin H, Jutrin I, et al. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med. 1993 Apr 15;118:577-81.


Abstract

Objective

To study the long-term effect of the angiotensin-converting enzyme inhibitor, enalapril, on the progress of diabetic nephropathy in patients with type 2 diabetes mellitus and normal blood pressure (BP) who had microalbuminuria.

Design

Randomized, double-blind, placebo-controlled trial with 5-year follow-up.

Setting

6 diabetes clinics coordinated by a university hospital in Israel.

Patients

108 patients with type 2 diabetes mellitus (World Health Organization criteria) and normal BP were recruited, and 94 (mean age 44 y, mean duration of diabetes 7 y, 55% women) completed the study. Inclusion criteria were age < 50 years; duration of diabetes < 10 years; no systemic, renal, cardiac, or hepatic diseases; body mass index (BMI) < 27 kg/m2; serum creatinine < 123 ┬Ámol/L (1.4 mg/dL); and microalbuminuria (urinary protein excretion of 30 to 300 mg/24 h).

Intervention

After a 2-month pretreatment period, 56 patients were allocated to enalapril, 10 mg/d, and 52 patients to placebo. Patients were followed for 5 years. Hypertension was treated with nifedipine.

Main outcome measures

Albuminuria, renal function (reciprocal creatinine), BP, diabetic retinopathy, fasting blood glucose, and glycosylated hemoglobin. Patients were seen every 3 to 4 months by their family physicians.

Main results

After 5 years, more patients in the placebo group developed overt proteinuria (> 300 mg/24 h) than did those in the enalapril group (P < 0.001) (Table). Mean albuminuria increased in the placebo group from 123 to 310 mg/24 hours but remained stable in the enalapril group (143 vs 140 mg/24 h). Renal function was stable in the enalapril group but decreased 13% over 5 years in the placebo group. After 2 years, the rate of renal function decline was greater in the placebo group (P < 0.05). The groups did not differ for BP, changes in BMI, or blood glucose or glycosylated hemoglobin levels.

Conclusions

Patients with type 2 diabetes mellitus, microalbuminuria, and normal blood pressure who received enalapril for 5 years had less deterioration in renal function and albuminuria than did patients who took placebo. The groups did not differ for changes in blood pressure, blood glucose, or glycosylated hemoglobin.

Source of funding: Nissenson-Tyomkin medical research grant.

For article reprint: Dr. M. Ravid, Department of Medicine A, Meir Hospital, Kfar-Saba 44281, Israel. FAX 972-97412135.


Table. Enalapril vs placebo at 5 years in patients with type 2 diabetes mellitus, normal blood pressure, and microalbuminuria*

Outcome Enalapril Placebo RRR (95% CI) NNT (CI)
Overt proteinuria 12% 42% 71% (37 to 87) 4 (3 to 9)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

Although cardiovascular disease is responsible for most deaths in type 2 diabetes, renal failure from diabetic nephropathy is also an important cause of morbidity and mortality. Once overt proteinuria develops, end-stage renal failure ensues within a few years, although treatment of hypertension can slow the loss of renal function. Microalbuminuria is a potent risk factor for development of renal failure in diabetes, and efforts to prevent nephropathy have focused on patients with this finding.

Treating patients who have normotensive type 1 diabetes and microalbuminuria with angiotensin-converting enzyme (ACE) inhibitors delays the development of overt proteinuria (1). No trial has been long enough, however, to determine whether this therapy affects the development of end-stage renal failure. The study by Ravid and colleagues extends these findings to patients with type 2 diabetes, normal BP, and microalbuminuria. Therapy with enalapril substantially reduced the rate of development of overt proteinuria, a clinically important end point, but the effect on change in serum creatinine, although statistically significant, was small.

Much longer trials are needed to determine whether treatment of normotensive type 2 diabetic patients with ACE inhibitors or other antihypertensive drugs delays or prevents end-stage renal failure. For the present, clinicians may reasonably choose to treat such patients who have microalbuminuria with the simple, well-tolerated medical regimen described here, based on consistent evidence that this therapy reduces the probability of developing clinical diabetic nephropathy.

William E. Clutter, MD
Washington University School of MedicineSt. Louis, Missouri, USA


Reference

1. Mathiesen ER, Hommel E, Giese J, Parving H. Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. BMJ. 1991;303:81-7.