Intensive blood pressure control doesn’t slow the progression of chronic kidney disease any better than standard blood pressure control in most patients, according to a report in the Sept. 2 New England Journal of Medicine.
It appears that the more intensive approach may benefit only patients who have proteinuria with a protein:creatinine ratio greater than 0.22, a value that is compatible with the widely accepted threshold of 300 mg/day for absolute urinary protein excretion, said Dr. Lawrence J. Appel of Johns Hopkins University, Baltimore, and his associates in the AASK (African-American Study of Kidney Disease and Hypertension) Collaborative Research Group.
Until now, “few trials have tested the effects of intensive blood pressure control [compared with conventional control] on the progression of chronic kidney disease, and the findings from such trials have been inconsistent. Despite a lack of compelling evidence, numerous guidelines recommend a reduced blood pressure target in patients with CKD,” they wrote.
Previous studies have rarely followed patients beyond 5 years, even though it typically takes longer than that for end-stage renal disease (ESRD) to develop in patients with CKD.
The AASK study compared outcomes between the two approaches to BP control in 1,094 black adults with mild to moderate hypertensive chronic kidney disease (defined as diastolic BP greater than 95 mm Hg and a glomerular filtration rate of 20-65 mL/min) but without marked proteinuria. Patients with diabetes were excluded from the trial.
In the first phase of the AASK investigation, patients were randomly assigned to either intensive BP control with a target of 92 mm Hg or lower mean arterial pressure (that is, lower than the usual target of 130/80 mm Hg recommended for CKD patients) or to conventional BP control with a target of 102-107 mm Hg mean arterial pressure (which corresponds to the conventional BP target of 140/90 mm Hg).
Throughout this initial phase of the trial, which lasted approximately 4 years, mean blood pressure was significantly lower in the intensive-control group (130/78 mm Hg) than in the standard-control group (141/86 mm Hg), yet there was no significant difference in the primary outcome of progression of kidney disease, development of ESRD, or death. Likewise, there was no significant difference between the two approaches in secondary or clinical outcomes.
In the second phase of the AASK investigation, patients who had not yet developed ESRD were invited to continue in a cohort portion of the trial, in which the BP target was 140/90 mm Hg. In 2004, when national guidelines were changed, this target was amended to lower than 130/80 mm Hg.
After a cumulative follow-up of 8-12 years, there still was no significant difference in primary or secondary outcomes between those who were initially assigned to the intensive-control and the standard-control groups. More intensive BP control did not slow the rate of progression of CKD, Dr. Appel and his associates reported (N. Engl. J. Med. 2010;363:918-29).
However, the intensive-control approach did benefit one subgroup of patients with proteinuria: those who had a protein:creatinine ratio of more than 0.22 at baseline. These patients showed a significant reduction in the primary outcome of progression of kidney disease, development of ESRD, or death, as well as in secondary and clinical outcomes.
The reason for this discrepancy is not known. “Overall, it is hard to develop a coherent, biologically plausible argument for a qualitative interaction between harm in patients without proteinuria and benefit in those with proteinuria,” the researchers said.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the Office of Research in Minority Health, and the National Institutes of Health. King Pharmaceuticals provided financial support and donated antihypertensive medications to each clinical center. Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn also donated antihypertensive drugs. None of these companies had any role in the design of the study, the accrual or analysis of data, or the preparation of the manuscript. Some of the investigators reported being in consultant and/or advisory board roles or receiving funds from numerous companies including Daiichi-Sankyo, Novartis, Amgen, King Pharmaceuticals, Abbott, Boehringer-Ingelheim, Litholink, Eli Lilly, Takeda, Merck, and Watson. Dr. Ingelfinger reported having no conflicts of interest.