Reduced Sodium Enhances ARB Effects
Lower sodium intake boosts the renal and cardiovascular (CV) protective effects of angiotensin receptor blockers (ARBs) in patients with type 2 diabetic nephropathy, according to a post-hoc analysis of data from two randomized clinical trials.
Among patients in the lowest tertile of sodium intake, those treated with an ARB (either losartan or irbesartan) experienced a significant 43% decreased risk of a renal event and a significant 37% decreased risk of a CV event compared with subjects treated with drugs that do not block the renin-angiotensin-aldosterone system (RAAS), investigators reported in Kidney International (2012;82:330-337).
Until further data are available, the researchers noted, they advocate that patients on RAAS-blocking drugs avoid high dietary sodium intake and recommend adherence to a guideline-suggested target of salt intake of 5-6 grams per day.
The investigators, led by Hiddo J. Lambers Heerspink, PhD, of University Medical Center Groningen, The Netherlands, defined a renal event as a composite of a confirmed doubling of serum creatinine from baseline or end-stage renal disease. They defined a CV event as a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, or revascularization procedures.
The researchers studied 1,117 patients with type 2 diabetic nephropathy who participated in the Angiotensin II Antagonist Losartan (RENAAL) trial and the Irbesartan Diabetic Nephropathy Trial (IDNT). During approximately three years of follow-up, 372 patients experienced a renal event and 392 experienced a CV event.
For patients in the second tertile of sodium intake, the risk of renal events was similar for both ARBs and non-RAAS treatment, whereas ARB treatment increased CV event risk by 2% compared with non-RAAS intervention. Among those in the highest tertile, ARBs were associated with a significant 37% increase in risk in renal event risk and a significant 25% increased CV event risk.
Sodium intake was determined by measuring 24-hour urinary sodium excretion. Urinary sodium excretion is a proxy for sodium intake, but is considered more reliable than food questionnaires, Dr. Lambers Heerspink's' group stated.
“Our study demonstrates that the renal and cardiovascular protective effects of ARBs are blunted in subjects with type 2 diabetes and nephropathy in whom dietary sodium intake is excessively high,” the authors wrote.
The authors acknowledged that their study had the limitation of being a retrospective analysis, so the results can only be interpreted as hypothesis generating. “It could be possible that the differences in patient's characteristics across tertiles of sodium intake have contributed to the enhanced effects of ARBs in the lower tertile of urinary sodium excretion.”