Renal protective effects of enalapril in hypertensive NIDDM: Role of baseline albuminuria

The primary results of a three-year prospective, double-blind, placebo-controlled trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti-hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors (J. Am Soc Nephrol 3: 335, 1992). The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis. Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m²]. Twenty-four hour urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and isotopically determined GFR were measured at baseline and six month intervals. Glycemic control and blood pressure regulation were assessed every three months. The rate of loss of GFR was significantly greater in patients with overt proteinuria at ne (UAE > 300 mg/24 hr) as compared to patients with baseline sub-clinical proteinuria (UAE ≤ 300 mg/24 hr). Antihypertensive treatment with enalapril preserved GFR significantly better (P < 0.01) in the patients with sub-clinical proteinuria at baseline (UAE ≤ 300 mg/24 hr) than other antihypertensive treatments which excluded the ACE inhibitor. Furthermore, only 7% of the enalapril-treated group progressed to clinical albuminuria compared to 21% of control treated patients. Although the enalapril-treated group had a lower mean blood pressure during the maintenance period, no correlation between blood pressure (systolic, diastolic or mean arterial) and rate of change of GFR was observed. Thus, enalapril treatment of hypertensive NIDDM patients with minimal or early renal disease provides a specific protective effect on the kidney which is additional to its blood pressure lowering effect. Angiotensin converting enzyme inhibitors should be used as initial treatment for hypertensive NIDDM patients with or without microalbuminuria and not be held in reserve until clinical albuminuria or proteinuria develops.