Lower blood pressure targets of unproven value in chronic kidney disease

Blood pressure targets less than 130/80 mm Hg in adults with chronic kidney disease (CKD) do not improve clinical outcomes more than a target of 140/90 mm Hg, a new study found. However, lower targets may benefit patients with proteinuria greater than 300 to 1,000 mg/d.

Researchers reviewed randomized, controlled trials and observational follow-up reports comparing blood pressure targets in adults with non-dialysis-dependent CKD. Results were published early online March 15 by Annals of Internal Medicine. Trials were eligible if they included patients with CKD (defined as glomerular filtration rate [GFR] less than 60 mL/min per 1.73 m², elevated urinary albumin level [>30 mg/d, or urinary albumin-creatinine ratio >0.03 g/g or dipstick-positive albuminuria], or elevated urinary protein level [>300 mg/d, or urinary protein-creatinine ratio >0.2 g/g]).

Three trials were included: the Modification of Diet in Renal Disease Study (MDRD), the African American Study of Kidney Disease and Hypertension Trial (AASK), and the Ramipril Efficacy in Nephropathy 2 study (REIN-2), with a total of 2,272 participants. After a mean two- to four-year follow-up, the main trial results did not show benefit for clinical outcomes.

A post-trial follow-up report from MDRD showed benefit of the lower target for kidney failure after about six years of follow-up. Subgroup analyses by baseline proteinuria levels in the MDRD and AASK trials (but not REIN-2) suggested benefit from the lower target in patients with proteinuria greater than 1,000 mg/d and urinary protein-creatinine ratio greater than 0.22 g/g, respectively. Treatment to a lower target required an average of 0.3 to 0.6 additional antihypertensive drugs per patient. A slightly higher rate of adverse events was suggested in the low target groups.

Although the point estimates in MDRD and AASK suggested that the low target might reduce kidney failure, the CIs around the estimates were wide and included the possibility of either important benefit or harm, the authors wrote. The only statistically significant result was in the MDRD Study follow-up, which showed a 23% reduction (95% CI, 18% to 43%) in the hazard for kidney failure in the group assigned to the lower target.

“We suggest that practitioners use discretion in patients with CKD and proteinuria and base the blood pressure target on individualized risk-benefit assessment and the patient's tolerance and preferences,” the authors wrote. “Treatment to a lower target may require greater vigilance to monitor for and avoid possible symptoms and adverse events from hypotension.” A major limitation of the evidence base is that the trials excluded type 1 diabetes and included very few patients with diabetic kidney disease. In addition, trial durations may have been too short to detect differences for clinically important outcomes, such as death and kidney failure.