Medline ® Abstracts for References 84,85
of 'Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults'
Effect of calcium channel or beta-blockade on the progression of diabetic nephropathy in African Americans.
Bakris GL, Mangrum A, Copley JB, Vicknair N, Sadler R
beta-Blockers are known to slow the progression of diabetic nephropathy by lowering arterial pressure. Moreover, in individuals with diabetic nephropathy, antihypertensive agents that provide sustained reductions in proteinuria slow the rate of decline in renal function compared with agents without this antiproteinuric effect. To examine whether differential effects on proteinuria affect the progression of diabetic nephropathy, we conducted a randomized study that compared the effects of a heart rate-lowering calcium channel blocker, sustained-release verapamil, with those of a beta-blocker, atenolol, on the progression of diabetic renal disease. The primary end point of the study was a change in creatinine clearance slope. Thirty-four African Americans with the following inclusion criteria were randomized to one of the two groups: serum creatinine greater than 1.4 mg/dL, proteinuria greater than 1500 mg/d, longer than a 5-year history of both non-insulin-dependent diabetes mellitus and hypertension, and exclusion of other renal diseases. Goal blood pressure was less than 140/90 mm Hg. All subjects received loop diuretics as second line agents to help achieve the blood pressure goal. Twenty-four-hour urinary protein and sodium excretions as well as creatinine clearance were measured at 6-month intervals. Blood pressure was measured every 3 months. After a mean follow-up of 54+/-6 months, the calcium channel blocker group demonstrated both a slower rate of decline in creatinine clearance (-1.7+/-0.9 versus -3.7+/-1.4 mL/min per year per 1.73 m2, P<.01) and a greater reduction in proteinuria compared with the atenolol group. Additionally, a greater proportion of the atenolol group had a 50% or more increase in serum creatinine compared with the verapamil group (32+/-9% versus 16+/-7%, P<.05). These between-group differences could not be explained by differences in blood pressure control. These data support the concept that antihypertensive agents that persistently maintain reductions in both arterial pressure and proteinuria slow the progression of diabetic renal disease in African Americans to a greater extent than those agents without these effects.
Department of Medicine, Ochsner Clinic, New Orleans, La, USA. email@example.com
Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study.
Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL
Ann Intern Med. 1995;123(10):754.
OBJECTIVE: To examine the relations among proteinuria, prescribed and achieved blood pressure, and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study.
DESIGN: 2 randomized trials in patients with chronic renal diseases of diverse cause.
SETTING: 15 outpatient nephrology practices at university hospitals.
PATIENTS: 840 patients, of whom 585 were in study A (glomerular filtration rate, 25 to 55 mliters/min.1.73 m2) and 255 were in study B (glomerular filtration rate, 13 to 24 mliters/min.1.73 m2). Diabetic patients who required insulin were excluded.
INTERVENTIONS: Patients were randomly assigned to a usual blood pressure goal (target mean arterial pressure,<or = 107 mm Hg for patients<or = 60 years of age and<or = 113 mm Hg for patients>or = 61 years of age) or a low blood pressure goal (target mean arterial pressure,<or = 92 mm Hg for patients<or = 60 years of age and<or = 98 mm Hg for patients>or = 61 years of age).
MAIN OUTCOME MEASURES: Rate of decline in glomerular filtration rate and change in proteinuria during follow-up.
RESULTS: The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01). Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A (r = -0.20; P<0.001) and study B (r = -0.34; P<0.001), and these correlations were stronger in persons with higher baseline proteinuria (P<0.001 in study A; P<0.01 in study B). In study A, the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial pressure. In both studies, the low blood pressure goal significantly reduced proteinuria during the first 4 months after randomization. This, in turn, correlated with a slower subsequent decline in glomerular filtration rate.
CONCLUSIONS: Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease. For patients with proteinuria of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable. The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of thistherapy in slowing the progression of renal disease.