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 measuresThe 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...

Effects of Intensive Low-Salt Diet Education on Albuminuria among Nondiabetic Patients with Hypertension Treated with Olmesartan

“…There were several short-term studies on the effect of restricting salt intake on BP and albuminuria reduction during RAAS blockade (6,9,10). Enhanced treatment effects of LSD education on albuminuria were observed in our study.…”

“…Several studies revealed an additive effect of dietary salt restriction with RAAS blockade on BP and proteinuria. However, most of these studies include a small number of patients (6,(9)(10)(11)20), and there has been no randomized, controlled study in Korean populations. Most importantly, the methods for implementing LSDs or high-salt diets used in previous studies offered strongly controlled or modulated diets (6,11), or they provided salt tablets (9), which are not suitable for application in typical clinical practice.…”

“…Blockade of the reninangiotensin-aldosterone system (RAAS) is well known to reduce urinary albumin excretion, and it is considered a mainstay of therapy in the prevention of ESRD (4,5). The antiproteinuric effect of the RAAS blockade can be magnified or reduced depending on the amount of dietary salt intake (6)(7)(8)(9)(10)(11).…”

Sodium Intake, ACE Inhibition, and Progression to ESRD

“…5 Inhibitors of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), are the antihypertensive drugs that most effectively reduce urinary proteins and slow GFR decline in patients with CKD. 1-3, 6 The efficacy of treatment, however, is heterogeneous and dependent on inborn 7 and environmental [8][9][10][11][12] factors. Data in experimental diabetes, 13,14 adriamycin nephrosis, 15 uninephrectomized rats, or in Munich Wistar rats with spontaneously reduced nephron numbers 16 uniformly show that expansion of the sodium pool, with glomerular hyperfiltration and activation of the renal RAS induced by enhanced sodium intake, all contribute to blunt the BP and proteinuria lowering effect of RAS inhibitors.…”

N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) predicts the cardio‐renal response to aliskiren in patients with type 2 diabetes at high renal and cardiovascular risk

“…Extracellular volume restriction, by means of moderating dietary sodium intake or concomitant diuretic treatment has been shown to improve the albuminuria‐reducing and blood pressure‐lowering response to RAAS blockade as well as the efficacy of RAAS blockade to decrease cardio‐renal risk 5, 14, 15. The present study shows that NT‐proBNP can help to identify individuals who may not respond to dual RAAS inhibition with aliskiren and who may benefit from diuretic treatment or dietary sodium‐lowering.…”