Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial

Abstract

Objective: To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose.

Design: Multicentre crossover randomised controlled trial.

Setting: Outpatient clinics in the Netherlands.

Participants: 52 patients with non-diabetic nephropathy.

Interventions: All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na(+)/day) and a regular sodium diet (target 200 mmol Na(+)/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label.

Main outcome measures: The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure.

Results: Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na(+)/day during a low sodium diet and 184 (6) mmol Na(+)/day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low sodium diet (9% (1)), to ACE inhibition.

Conclusions: Dietary sodium restriction to a level recommended in guidelines was more effective than dual blockade for reduction of proteinuria and blood pressure in non-diabetic nephropathy. The findings support the combined endeavours of patients and health professionals to reduce sodium intake. Trial registration Netherlands Trial Register NTR675.

Fig 1 Additional effect of low sodium diet, angiotensin receptor blockade (ARB), or both on proteinuria during angiotensin converting enzyme (ACE) inhibition. Data are geometric mean with 95% confidence interval. *P<0.05 v ACE inhibition on regular sodium diet. †P<0.05 v ACE inhibition plus ARB on regular sodium diet. ‡P<0.05 v ACE inhibition on low sodium diet

Fig 2  Additional effect of low sodium diet, angiotensin receptor blockade (ARB), or both on systolic blood pressure during angiotensin converting enzyme (ACE) inhibition. Data are mean with 95% confidence interval. *P<0.05 v ACE inhibition on regular sodium diet. †P<0.05 v ACE inhibition plus ARB on regular sodium diet

Fig 3 Additional effect of low sodium diet, angiotensin receptor blockade (ARB), or both on diastolic blood pressure during angiotensin converting enzyme (ACE) inhibition. Data are mean with 95% confidence interval. *P<0.05 v ACE inhibition on regular sodium diet. †P<0.05 v ACE inhibition plus ARB on regular sodium diet