THE STUDY OF THE EFFECT OF INTENSITY OF BLOOD-PRESSURE MANAGEMENT ON THE PROGRESSION OF TYPE-1 DIABETIC NEPHROPATHY - STUDY DESIGN AND BASE-LINE PATIENT CHARACTERISTICS

A randomized, prospective, clinical trial has been initiated to contin ue follow-up in a subset of the patients previously enrolled in the re cently completed Study of Angiotensin-Converting Enzyme Inhibition (AC Ei) in Type 1 Diabetic Nephropathy. In that study, the use of captopri l was associated with a 48% reduction in the risk of doubling the seru m creatinine and a 50% reduction in the risk of experiencing dialysis, transplantation, or death, compared with the use of placebo. These ef fects were independent of captopril's effect on the blood pressure. Th is study is designed to determine whether the level of mean arterial b lood pressure (MAP), using the ACE inhibitor ramipril as the primary t herapy, is associated with an improved prognosis of diabetic nephropat hy with respect to (1) the rate of decline in renal function; (2) the rate of progression to end-stage renal failure; (3) the clinical cours e of proteinuria; (4) morbidity; and (5) mortality. Patients are rando mized into one of two distinct blood pressure control groups, an Inten sive Group #1, MAP less than or equal to 92 mm Hg; and a Moderate Grou p #2, MAP 100 to 107 mm Hg. Patients previously enrolled in the ''Stud y of ACEi in Type 1 Diabetic Nephropathy'' whose serum creatinine was less than 4.0 mg/dL (354 mu mol/L) were eligible for randomization int o this study. All patients will receive ramipril (2.5 to 10.0 mg/day) as the primary therapy, with the addition or removal of other antihype rtensive agents as needed to achieve the assigned blood pressure goal. Baseline characteristics of the cohort (N = 128) at entry into this s tudy are (percent or mean +/- SD): male, 48%; age, 37 +/- 7 yr; durati on of diabetes, 26 +/- 7 yr; history of hypertension, 77%; serum creat inine, 150 +/- 71 mu mol/L(1.7 +/- 0.8 mg/dL); (I-125)iothalamate GFR (I-GFR), 65 +/- 37 mL/min per 1.73 m(2); 24-h urine protein, 2.0 +/- 2 .4 g/24 h; total glycosylated hemoglobin, 11.7 +/- 2.8% (normal, 4 to 8%); 24-h urine urea nitrogen, 9.3 +/- 3.5 g/24 h; and blood pressure, 132/79 +/- 19/11 mm Hg (MAP, 97 mm Hg). There were no statistically s ignificant differences between the baseline characteristics of Groups 1 and 2. At randomization, 63% of the patients in Group 1 (MAP less th an or equal to 92 mm Hg) had a MAP >92 mm Hg and required further bloo d pressure reduction. In Group 2 (MAP greater than or equal to 100 les s than or equal to 107 mm Hg), 20% of the patients had a MAP >107 mm H g and 66% of the patients had a MAP <100 mm Hg. Patients will receive I-GFR determination at baseline, at every 8 months thereafter, and at exit, for a total of four I-GFR measurements over a 2-yr study period. The effect of blood pressure on the rate of deterioration in renal fu nction will be determined by comparing the slopes of the GFR versus ti me in each of the two blood pressure groups.