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


Captopril reduced progression of microalbuminuria in normotensive type 1 diabetes

ACP J Club. 1994 July-Aug;121:11. doi:10.7326/ACPJC-1994-121-1-011

Source Citation

Viberti G, Mogensen CE, Groop LC, Pauls JF, for the European Microalbuminuria Captopril Study Group. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994 Jan 26;271:275-9.



To determine if captopril decreases the rate of progression from microalbuminuria to clinical proteinuria in patients with normal blood pressure and type 1 diabetes mellitus.


2-year randomized, double-blind, placebo-controlled trial.


11 hospital-based diabetes centers in Europe and 1 in Asia.


92 patients (mean age 32 y) who had developed type 1 diabetes before the age of 39 years, were between the ages of 18 and 55 years, and had diabetes for 4 to 28 years. Patients' albumin excretion rate (AER) was 20 to 200 µg/min. The arterial pressure was < 160/95 mm Hg in patients ≥ 35 years and < 145/90 mm Hg in patients < 35 years. Exclusion criteria were treatment with antihypertensive or nonsteroidal anti-inflammatory drugs, or aldose-reductase inhibitors; brittle diabetes; insulin resistance; history of poor compliance; increased serum creatinine and serum potassium concentrations; or other systemic diseases. Follow-up was 83%.


Patients were randomized in blocks of 2 at each center to receive captopril, 50 mg (n = 46), or placebo (n = 46) twice a day after a 4-week placebo lead-in period. Compliance was assessed by counting tablets at each trimonthly visit.

Main outcome measures

Progression to clinical proteinuria, defined as an AER > 200 µg/min and ≥ 30% increase from baseline, and rate of change in AER. Progression to arterial hypertension and changes in the glomerular filtration rate (GFR) were secondary outcome measures.

Main results

Analysis was by intention to treat. Progression to proteinuria was greater in the group receiving placebo than in the group receiving captopril (P = 0.05) (Table). AER increased from 52 µg/min to 76 µg/min over 24 months in patients receiving placebo and decreased from 52 µg/min to 41 µg/min in patients receiving captopril (between group difference, P < 0.01). No difference was noted between groups for mean arterial pressure or GFR at the study end, although mean blood pressure decreased at several time points in the captopril group.


Treatment with captopril reduced the rate of progression to clinical proteinuria in patients with type 1 diabetes mellitus and microalbuminuria.

Source of funding: Bristol-Myers Squibb Institute for Pharmaceutical Research.

For article reprint: Dr. G. Viberti, Unit for Metabolic Medicine, UMDS-Guy's Hospital, Fifth Floor, Thomas Guy House, London, England SE1 9RT, United Kingdom. FAX 44-171-955-2985.

Table. Captopril vs placebo for normotensive patients with type 1 diabetes*

Outcome at 24 mo Captopril Placebo RRR (95% CI) NNT (CI)
Progression to proteinuria 9% 26% 67% (10 to 88) 6 (3 to 51)

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


The study by Viberti and colleagues and other long-term clinical investigations of angiotensin-converting enzyme (ACE) inhibitors have established a strong association between a blunted increase in albuminuria and a slowed progression of diabetic nephropathy (1). This association has been shown in patients with diabetes who have either hypertension or normal blood pressure (1). Unfortunately, in most studies, as in this study, patients who received ACE inhibitors had substantial and sustained reductions in blood pressure when compared with controls at some point in the trial. Parving and colleagues (2) showed that the level of arterial pressure reduction strongly correlated with renal preservation. Thus, lower blood pressures may have contributed, in part, to the "renal-preserving" effects of ACE inhibitors.

Recent studies in persons with diabetes and hypertension, however, clearly show that ACE inhibitors preserve renal function independent of blood pressure reduction (1, 3). These studies not only confirm the concept that a blunted increase in albuminuria over time strongly correlates with preservation of renal function but also show that these agents prevent scarring of the glomerus and mesangial volume expansion, the morphologic hallmark of diabetic nephropathy seen on kidney biopsy specimens (3). Thus, the available data support the early use of an ACE inhibitor in patients with diabetes and microalbuminuria.

George L. Bakris, MD
Rush Presbyterian-St. Luke's Medical CenterChicago, Illinois, USA


1. Bakris GL. Calcium abnormalities and the diabetic, hypertensive patient: implications for renal preservation. In: Epstein M, ed. Calcium Antagonists in Clinical Medicine. Philadelphia: Hanley & Belfus Inc; 1992:367-89.

2. Parving HH, Smite UN, Amities ER, Hommel E. Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy [Abstract]. J Am Soc Nephrol. 1990;1:294.

3. Bakris GL. Angiotensin-converting enzyme inhibitors and progression of diabetic nephropathy [Editorial]. Ann Intern Med. 1993;118:643-4.