Enalapril for diabetic nephropathy
ACP J Club. 1992 July-Aug;117:12. doi:10.7326/ACPJC-1992-117-1-012
Björck S, Mulec H, Johnsen SA, Nordén G, Aurell M. Renal protective effect of enalapril in diabetic nephropathy. BMJ. 1992 Feb 8;304:339-43.
To determine the effectiveness of enalapril compared with metoprolol in reducing the rate of decline of kidney function in patients with diabetic nephropathy.
Randomized trial with a mean follow-up of 2.2 years.
3 outpatient nephrology clinics in Sweden.
40 patients (mean age, 42 y; mean duration of diabetes, 25 y) with insulin-dependent diabetes, diabetic nephropathy, reduced renal function, and retinopathy were included. All but 2 patients were receiving antihypertensive medication before the study. Exclusion criteria were previous treatment with angiotensin-converting enzyme inhibitors, pregnancy, uremia, and other conditions affecting renal function. 36 patients were followed for a minimum of 6 months and formed the basis of the analyses. The pretreatment mean glomerular filtration rates (GFRs) were 46 and 48 mL/min per 1.73 m2 in the enalapril and metoprolol groups, respectively.
Prestudy antihypertensive treatment except furosemide was stopped at least 2 days before randomization. Patients were assigned to enalapril (n = 22) or metoprolol (n = 18). The enalapril dose was adjusted using the baseline GFR and mean arterial blood pressure resulting in a mean dose of 11 mg/d. Metoprolol was doubled every week to a maximum of 200 mg, which resulted in a mean dose of 144 mg/d. If the mean arterial blood pressure was still not within the goals set by the study, patients were treated with furosemide, hydralazine, or nifedipine.
Main outcome measure
Rate of decline in GFR measured by chromium-51 edetic acid clearance.
The rate of decline of the GFR was significantly lower in patients treated with enalapril (2.0 [SD 3.2] vs. 5.6 [SD 5.9] mL/min per y; P = 0.021). Patients treated with enalapril showed an early (first 6 mo) fall in GFR with no further significant decline, whereas the decline was continuous in patients treated with metoprolol. Urinary excretion of albumin and protein was reduced only in patients treated with enalapril. Mean arterial blood pressure was 102 mm Hg in the enalapril group and 103 mm Hg in the metoprolol group. 7 patients from each treatment group were withdrawn during the study. 3 patients in each group progressed to end-stage renal disease.
Treatment of patients with diabetic nephropathy with enalapril resulted in a lower rate of decline of kidney function than did treatment with metoprolol and achieved similar blood pressure control.
Sources of funding: Swedish Medical Research Council and Merck Sharp & Dohme.
Address for article reprint: Dr. S. Björck, Department of Nephrology, Sahlgrenska Hospital, University of Göteborg,S-413 45 Göteborg, Sweden.
Diabetic end-stage renal disease is a devastating and common complication of diabetes, causing 35% of the annual new cases of end-stage renal disease in the United States. When renal disease is established, blood pressure surpasses glycemic control as a risk factor for further clinical decline. Recently, angiotensin-converting enzyme (ACE) inhibitors have been touted to be more effective than other antihypertensives in slowing progression. Much of the evidence for this comes from animal models or small, nonrandomized trials. Björck and colleagues' randomized trial represents a significant contribution to this evidence. Although the numbers are small (40 patients entered; 14 dropouts) and the follow-up is short (2 y), the results are still significant. Enalapril slows the rate of decline in glomerular filtration more than does metoprolol despite similar blood pressure control. Both groups, however, had similar rates of progression to end-stage renal disease. Longer term follow-up could help to determine whether this more important outcome diverges later.
For clinicians caring for patients with diabetes, blood pressure control is crucial for preserving renal function. Blood pressure goals should be individually determined, but, if tolerated, mean arterial pressures between 100 and 110 mm Hg should be sought. ACE inhibitors should be used unless the patient has hyperkalemia or known renal artery stenosis. Renal function should be monitored closely in the first 6 months to detect an early decline. Some experts suggest use of ACE inhibitors in patients with microalbuminuria without hypertension (1). Look for the results of a larger trial in insulin-dependent patients sponsored by the National Institutes of Health.
Jacqueline A. Pugh, MD
Audie L. Murphy Memorial Veterans Hospital San Antonio, Texas