Vogt L et al. (2008) Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol 19: 999–1007

A high sodium intake inhibits the renoprotective effect of blockade of the renin–angiotensin–aldosterone system (RAAS). Vogt et al. investigated the combined effects of a low-sodium diet and the diuretic hydrochlorothiazide on proteinuria and blood pressure in Dutch patients receiving the angiotensin-receptor blocker losartan.

The study cohort comprised 33 nondiabetic patients with stable proteinuria (24 male; mean age 50 years; mean BMI 27.5 kg/m2). The mean baseline proteinuria was 3.8 g/day. Patients were randomized to a high-sodium (200 mmol/day) or a low-sodium (50 mmol/day) diet for 18 weeks; they then switched to the other diet for a further 18 weeks. During both 18-week periods, patients received each of the following for 6 weeks, in random order: placebo; losartan (100 mg/day); and losartan (100 mg/day) plus hydrochlorothiazide (25 mg/day).

Proteinuria was reduced by 22% from baseline with the low-sodium diet alone and by 30% with losartan alone. The reduction in proteinuria was greater when losartan was combined with a low-sodium diet (55%) or with hydrochlorothiazide (56%), but it was greatest when losartan was combined with both a low-sodium diet and hydrochlorothiazide (70%). A similar pattern was observed for blood pressure reduction. The additive antiproteinuric effects of a low-sodium diet and hydrochlorothiazide were particularly pronounced in patients who responded poorly to losartan alone.

The authors conclude that a low-sodium diet and a diuretic are equally effective at enhancing the antihypertensive and antiproteinuric effects of RAAS blockade—and are particularly beneficial in patients who are resistant to RAAS blockade alone—but note that the increase in efficacy is greatest when the two interventions are combined.