"Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis

Abstract

"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 (DBF) 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 nitration rate. Eighty-seven non-diabetic patients (age 25 to 73; 68 black, 58 male) with long-standing hypertension (DBP ≥ 95 mm Hg), chronic renal insufficiency (GFR ≤ 70 m/min/1.73 m2) and a normal urine sediment were studied. DBP was pharmacologically lowered 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 125I-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 m2/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 m2/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 ESRD) 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 m2/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.