Intensive Blood Pressure Control in Patients with Hypertensive Chronic Kidney Disease

The prevalence of chronic kidney disease in adults in the United States increased from 10% for the period 1988-1994 to 13% for the period 1999-2004. The cost to the federal government to treat end-stage renal disease (ESRD) was $23 billion in 2004; the corresponding treatment for chronic kidney disease was $49 billion, according to researchers. Studies have shown that approximately 30% of incident cases of ESRD are attributed to hypertension; the burden of hypertension-related chronic kidney disease and ESRD is particularly high among black patients. The relationship between blood pressure and the progression of chronic kidney disease or incident ESRD is direct and progressive, according to previous observational studies. Researchers recently conducted a study called AASK (African-American Study of Kidney Disease and Hypertension) to assess the effects of an intensive blood pressure target on the progression of chronic kidney disease among black patients with hypertensive chronic kidney disease. Following completion of the trial phase of the study, patients were eligible to enroll in a cohort phase in which they received recommended therapy with a blood pressure target of <130/80 mm Hg. The researchers combined data from both phases of the trial to obtain information on the long-term effects of a lower blood pressure target on the progression of chronic kidney disease. They reported findings in the New England Journal of Medicine [2010;363(10):918-929].

The trial included 1094 black patients with hypertensive chronic kidney disease who were randomly assigned to receive either intensive or standard blood pressure control; participants were then invited to enroll in the second (cohort) phase. The primary clinical outcome in the second phase was the progression of chronic kidney disease (doubling of the serum creatinine level, diagnosis of ESRD, or death). Follow-up ranged from 8.8 to 12.2 years. At baseline, the mean blood pressure in the intensive-control group was 152/96 mm Hg and 149/95 mm Hg in the standard-control group. During the trial phase, mean blood pressure in the intensive-control group was 130/78 mm Hg; in the standard-control group, mean blood pressure during the trial phase was 141/86 mm Hg. Differences in blood pressure during the cohort phase were smaller, because all patients had the same blood pressure target. Mean blood pressure in the intensive-control group was 131/78 mm Hg, compared with 134.78 mm Hg in the standard-control group. In both phases of the study, there was no significant difference between the intensive-control group and the standard-control group in the primary outcome (hazard ratio [HR] in the intensive-control group, 0.91; 95% confidence interval [CI], 0.77-1.08; P=.27); there was no difference in secondary outcomes between the 2 groups. The effects of the intensive blood pressure control differed according to baseline level of proteinuria (P=.02 for interaction).

The study found a potential reduction in the risk of the primary outcome in patients with a protein-to-creatinine ratio of >0.22 (HR, 0.73; 95% CI, 0.58-0.93; P=.01). Those patients also had a reduction in risk for 2 of the secondary outcomes: a doubling of the serum creatinine level or ESRD (HR, 0.76; 95% CI, 0.58-0.99; P=.04) and ESRD or death (HR, 0.67; 95% CI, 0.52-0.87; P=.002). The researchers cited some limitations to the study: (1) the cohort phase was not a randomized trial because all participants had the same blood pressure target; (2) adjustment of therapy was based on blood pressure assessed by standard office readings rather than ambulatory blood pressure; and (3) the effect modifier that accounted for the observed findings might not be the presence of proteinuria at baseline but might be a variable closely related to it. In conclusion, the researchers summarized that “although guidelines have recommended a more intensive blood pressure goal in patients with hypertensive chronic kidney disease, trial evidence in support of such recommendations is sparse.”