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Am Fam Physician. 2003;67(10):2207-2212

Compared with white Americans, blacks are six times more likely to develop hypertension-related end-stage renal disease. In the African American Study of Kidney Disease and Hypertension, Wright and colleagues attempted to determine whether lowering blood pressure would slow the decline in glomerular filtration rate. They also compared the effects of three antihypertensive drugs to ascertain whether drug class would affect the progression of kidney disease.

The study included 1,094 self-identified blacks with hypertensive kidney disease (18 to 70 years of age). The participants were randomized to a usual diastolic blood pressure goal (102 to 107 mm Hg) or a lower-than-usual diastolic blood pressure goal (92 mm Hg or less), and to a ramipril versus metoprolol treatment group or an amlodipine versus metoprolol treatment group. The study participants were followed for three to six years or more. For each participant, the baseline glomerular filtration rate was obtained (two measurements), with follow-up measurements at three and six months, and then every six months thereafter. In addition to glomerular filtration rate, information about clinical outcomes (end-stage renal disease [dialysis or transplantation], death, and proteinuria) was included for secondary analysis.

The glomerular filtration rate initially declined more quickly in the group with the lower diastolic blood pressure goal than in the group with the usual goal. Over the rest of the study period, declines in the glomerular filtration rate did not differ significantly in the groups. The groups displayed no differences in the main clinical composite outcomes.

In the ramipril versus metoprolol group, glomerular filtration rate initially declined more slowly in the ramipril group, but there were no significant differences between groups for the remainder of the study period. A statistically significant decreased risk (22 percent) for the main composite clinical end points occurred in the group using ramipril compared with metoprolol.

In the amlodipine versus metoprolol group, the net decline in glomerular filtration rate was slower in the amlodipine group than in the metoprolol group. However, in the chronic phase of the comparison, the glomerular filtration rate declined more slowly in the metoprolol group. Risk reduction for the main clinical composite outcomes was not significant with either medication, but a significant risk reduction occurred for end-stage renal disease and death or end-stage renal disease alone in the metoprolol group.

In subsets with and without proteinuria, slight trends favored a lower blood pressure goal in the participants who had higher degrees of proteinuria. Those with higher degrees of proteinuria showed an initial trend for slower decline in the glomerular filtration rate, while the opposite occurred in participants with little or no proteinuria. The differences were not maintained during the chronic phase of treatment.

The authors conclude that lowering blood pressures below the levels recommended for other end-organ damage does not slow decline in the glomerular filtration rate. They note that there may be some additional protective effect from lowering blood pressure below usual levels when proteinuria of 1 g per day or higher is present. Although no drug class showed significant effects on the decline in glomerular filtration, ramipril did better than the other two regimens in its effect on main clinical composite outcome and other secondary analysis outcomes, and metoprolol did better than amlodipine with respect to end-stage renal disease alone, as well as end-stage renal disease and death.

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