STRICT BLOOD-PRESSURE CONTROL AND PROGRESSION OF RENAL-DISEASE IN HYPERTENSIVE NEPHROSCLEROSIS

Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease (ESRD) in blacks in the United States. It is generally believed that hypertensive renal injury is responsible for progressive renal failure; however, it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease. Accordingly, we performed a long-term prospective randomized trial to determine whether ''strict'' [diastolic blood pressure (DBP) 65 to 80 mm Hg] versus ''conventional'' (DBP 85 to 95 mm Hg) blood pressure control is associated with a slower rate of decline in glomerular filtration rate. Eighty-seven non-diabetic patients (age 25 to 73; 68 black, 58 male) with long-standing hypertension (DBP greater than or equal to 95 mm Hg), chronic renal insufficiency (GFR less than or equal to 70 m/min/1.73 m(2)) and a normal urine sediment were studied. DBP was pharmacologically lowered to less than or equal to 80 mm Hg (3 of 4 consecutive measurements at 1 to 4 weeks intervals) after which patients were randomized. DBP and GFR (renal clearance of I-125-iothalamate) were measured at baseline, at three months and every six months post randomization. The rate of decline in GFR (GFR slope, in ml/min/ 1.73 m(2)/year), estimated by the method of maximum likelihood in a mixed effects model, was the primary outcome variable. In a secondary analysis, 50% reduction in GFR (or a doubling of serum creatinine) from baseline, ESRD and death were combined. Also the rate of decline in GFR in blacks and non-blacks was compared. Mean follow-up was 40.5 +/- 1.8 months in the ''strict'' and 42.2 +/- 2.1 month in the ''conventional'' groups. Mean follow-up DBP was 81 +/- 1 mm Hg in the ''strict'' and 87 +/- 1 mm Hg in the ''conventional'' groups (P < 0.0001, 95% C.I. for the difference -8.4 to -3.1). GFR slope was -0.31 +/- 0.45 in the ''strict'' and -0.050 +/- 0.50 ml/min/1.73 m(2)/year in the ''conventional'' group (P > 0.25, 95% C.I. for the difference -1.60 to 1.08). The mean slopes were not significantly different from zero. Twelve (7 with ESRD) of 42 ''strict'' and 7 (2 with ERD) of 35 ''conventional'' (2 ESRD) patients experienced a clinical endpoint in the time to event analysis (P > 0.25). Mean follow-up DBP was 85 +/- 1 in blacks and 79 +/- 1 in non-blacks (P < 0.01, 95% C.I. 2.3 to 9.8); however, GFR slope in blacks (N = 58) was -0.016 +/- 0.37 Versus -0.27 + 0.76 ml/min/1.73 m(2)/year in non-blacks (P < 0.25). We conclude that in hypertensive nephrosclerosis ''strict'' control of blood pressure to a mean DBP of 81 +/- 0.8 mm Hg did not conserve renal function better than ''conventional'' control of blood pressure to a mean of 86.7 +/- 1.1 mm Hg. However, both ''strict'' and ''conventional'' blood pressure control are associated with a very slow overall mean rate of decline in GFR. In addition, we found that long-term blood pressure lowering was associated with a similar slow rate of decline in GFR in blacks and non-blacks. Application of this quality of blood pressure control could significantly reduce the incidence of ESRD in the United States.