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 > or = 95 mm Hg), chronic renal insufficiency (GFR < or = 70 m/min/1.73 m2) and a normal urine sediment were studied. DBP was pharmacologically lowered to < or = 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract-We evaluated the blood pressure-lowering activity, tolerability, and safety of losartan in 112 hypertensive (sitting diastolic blood pressure, 90 to 115 mm Hg) patients with chronic renal insufficiency including mild renal insufficiency (30 to 60 mL/min per 1.73 m 2 ; nϭ51), moderate to severe renal insufficiency (10 to 29 mL/min per 1.73 m 2 ; nϭ33), or hemodialysis (nϭ28). After a 3-week placebo period, once-daily losatan was administered for 12 weeks. The daily dose of 50 mg was increased to 100 mg after 4 weeks in patients whose sitting diastolic blood pressure remained Ն90 mm Hg or was reduced by Ͻ5 mm Hg. A second, non-angiotensin-converting enzyme inhibitor, antihypertensive drug was added after 8 weeks as needed. Twenty-four-hour creatinine clearance was determined and renal clearance studies of inulin and para-aminohippurate were done in a subset of 11 patients. Trough sitting blood pressures were reduced at the end of the first week in all groups. At weeks 4, 8, and 12, the reductions in systolic blood pressure/diastolic blood pressure averaged Ϫ11.9/Ϫ8.7, Ϫ10.8/Ϫ9.4, and Ϫ14.7/Ϫ12.1 mm Hg in patients with mild renal insufficiency; Ϫ7.7/Ϫ6.3, Ϫ13.1/ Ϫ11.8, and Ϫ14.1/Ϫ10.6 mm Hg, in moderate to severe renal insufficiency; Ϫ17.0/Ϫ12.7, Ϫ19.1/Ϫ14.4, and Ϫ22.7/Ϫ18.0 mm Hg in hemodialysis. Creatinine clearance, glomerular filtration rate, and effective renal plasma flow were stable. Losartan was withdrawn in only 6 patients because of a clinical or laboratory adverse experience. Hyperkalemia (Ͼ6 mEq/L) requiring discontinuation of losartan occurred in only one (group 2) patient. We conclude that once-daily losartan, given as monotherapy at doses of 50 or 100 mg or in combination with other antihypertensive drugs, was effective in reducing blood pressure in hypertensive patients with chronic renal disease and that losartan regimens were well tolerated in all groups, including those on hemodialysis. (Hypertension. 1998;31:684-691.)

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Seventy-nine hypertensive nephrosclerosis patients i entered a prospective randomized singleblind study to 1) establish the pattern of decay of renal function in this population and the variability therein and 2) to determine if strict diastolic blood pressure (DBP) control (<80 mm Hg) is more effective than conventional levels (90-95 mm Hg) in conserving renal function. Because of unexpected significant improvement in renal function in patients from both groups, which changed the perspectives on the course of this disease as described herein, this report is being published before completion of the trial. The selection criteria were 1) serum creatinine concentration of 1.6-7.0 mg/dl, 2) glomerular filtration rate of less than 70 ml/min/1.73 m 2 , and 3) absence of diseases (other than hypertension) known to destroy renal function. Renal function was assessed by glomerular filtration rate ([ l2S I]iothalamate clearance) and serum creatinine concentration. Before randomization, DBP was aggressively treated to reduce it to less than 80 mm Hg. Twenty-two subjects (14 in the strict DBP control group and eight in the conventional DBP control group) have been enrolled in the study for 36 months. In contrast to results from previous studies in humans and rats, renal function improved in both patient groups. Thus, irrevocable progression of renal damage after onset of renal failure from high blood pressure does not necessarily occur, and in fact, long-term improvement of renal function resulted from the effects of the study itself. The study design involving the 2-4-month initial period of aggressive DBP control at 80 mm Hg or less followed by control of DBP at less than 90 mm Hg was associated with long-term improvement in renal function. (Hypertension 1989; 13:766-772)