The results from this study add to a growing pool of evidence that patients with early proteinuria may be good targets for intense BP control. A systematic review by Upadhyay et al (Ann Intern Med 2011;154:541-548) reviewed three trials and their data regarding BP control, kidney disease and proteinuria.
These studies include the Modification of Diet in Renal Disease (MDRD) study, the African American Study of Kidney Disease and Hypertension (AASK), and the Ramipril Efficacy in Nephropathy 2 (REIN-2) trial. The MDRD study followed 585 patients with an eGFR of 25-55 and 255 patients with an eGFR of 13-24.
These patients were randomized to a usual or high protein diet and to one of two BP targets: 140/90 or 130/80 mm Hg. ACE inhibitors were favored, followed by calcium channel blockers. In the AASK trial, patients were stratified into one of three medication regimens and were stratified into either a normal or low BP target group.
The REIN-2 trial included individuals with proteinuria of 1,000-3,000 mg/day and creatinine clearance less than 45 mL/min and those with proteinuria above 3,000 mg/day and creatinine clearance below 70. Individuals were stratified into either a normal or low BP group and treated with felodipine in addition to their other medications.
None of the trials demonstrated a direct benefit of a low BP goal in reducing complications during the trials. With respect to proteinuria, AASK trial results demonstrated that subjects with low BP targets who had a protein/creatinine ratio above 0.22 g/g (approximately more than 300 mg proteinuria/day) had significantly improved outcomes during the trial and follow up.
The MDRD study demonstrated a benefit in low BP targets for patients with greater than 1000 mg proteinuria/day in trial A and more than 3,000 mg proteinuria/day in trial B.
Adverse Drug Effects
The primary concern with intensive BP control regimens is the potential adverse complications from the medications themselves. Each trial showed an increase in adverse events in the low BP groups that were attributed to higher doses of medication.
Overall, though, the data from these studies indicate that more conservative BP goals do confer benefits in the presence of proteinuria. Therefore, more rigorous sodium restrictions may be of benefit when trying to reach these goals by helping reduce the necessary dosages.
Current guidelines from the Kidney Disease Outcomes Quality Initiative (KDOQI) recommend a sodium restriction of 2,000 mg/day. Meanwhile, the 2010 Dietary Guidelines for Americans recommends a reduction of sodium to 1,500 mg/day for at-risk individuals, including those with hypertension.
These guidelines are often tough for new patients without adequate dietary education, but evidence supports the need for a stronger nutritional intervention in controlling BP, especially for patients with elevated proteinuria. In addition, these data may offer potential as a screening tool for gauging appropriate dietary interventions.