Intensive blood-pressure control in hypertensive chronic kidney disease

Abstract

Background: In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients.

Methods: We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years.

Results: During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01).

Conclusions: In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)

Figure 1. Blood-Pressure Levels in Patients with Chronic Kidney Disease

Shown are median systolic (Panel A) and diastolic (Panel B) blood-pressure measurements for patients who received intensive blood-pressure control or standard control over time in the trial and cohort phases. All values are for patients who did not have progression of chronic kidney disease, defined as a doubling of the serum creatinine level, end-stage renal disease, or death (composite primary outcome). The upper edge of each bar corresponds to the 75th percentile, and the bottom edge to the 25th percentile. Patients had at least 3 years of follow-up in the trial phase. The period between 3 and 6.5 years is a mixed period that encompasses the trial phase for early enrollees and the cohort phase for late enrollees. After 6.5 years, all data are for the cohort phase. The values at the bottom of the graphs are the mean difference in blood pressure between the intensive-control group and the standard-control group at various time points; numbers in parentheses are 95% confidence intervals.

Figure 2. Cumulative Incidence of the Composite Primary Outcome, According to Baseline Proteinuria Status

Among patients with baseline proteinuria, which was defined as a urinary protein-to-creatinine ratio (P:C) of more than 0.22, those who received intensive blood-pressure control had a significantly lower cumulative incidence of the composite primary outcome (a doubling of the serum creatinine level, end-stage renal disease, or death) than those who received standard blood-pressure control (hazard ratio in the intensive-control group, 0.73; 95% confidence interval [CI], 0.58 to 0.93; P = 0.01). However, the between-group difference was not significant among patients with a P:C of 0.22 or less (hazard ratio, 1.18; 95% CI, 0.93 to 1.50; P = 0.16). The values at the bottom of the graph are numbers of patients.