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Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial.
BMJ. 2011 Jul 26; 343:d4366.BMJ

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.

Authors+Show Affiliations

Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21791491

Citation

Slagman, Maartje C J., et al. "Moderate Dietary Sodium Restriction Added to Angiotensin Converting Enzyme Inhibition Compared With Dual Blockade in Lowering Proteinuria and Blood Pressure: Randomised Controlled Trial." BMJ (Clinical Research Ed.), vol. 343, 2011, pp. d4366.
Slagman MC, Waanders F, Hemmelder MH, et al. Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial. BMJ. 2011;343:d4366.
Slagman, M. C., Waanders, F., Hemmelder, M. H., Woittiez, A. J., Janssen, W. M., Lambers Heerspink, H. J., Navis, G., & Laverman, G. D. (2011). Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial. BMJ (Clinical Research Ed.), 343, d4366. https://doi.org/10.1136/bmj.d4366
Slagman MC, et al. Moderate Dietary Sodium Restriction Added to Angiotensin Converting Enzyme Inhibition Compared With Dual Blockade in Lowering Proteinuria and Blood Pressure: Randomised Controlled Trial. BMJ. 2011 Jul 26;343:d4366. PubMed PMID: 21791491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial. AU - Slagman,Maartje C J, AU - Waanders,Femke, AU - Hemmelder,Marc H, AU - Woittiez,Arend-Jan, AU - Janssen,Wilbert M T, AU - Lambers Heerspink,Hiddo J, AU - Navis,Gerjan, AU - Laverman,Gozewijn D, AU - ,, Y1 - 2011/07/26/ PY - 2011/7/28/entrez PY - 2011/7/28/pubmed PY - 2011/10/1/medline SP - d4366 EP - d4366 JF - BMJ (Clinical research ed.) JO - BMJ VL - 343 N2 - 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/21791491/Moderate_dietary_sodium_restriction_added_to_angiotensin_converting_enzyme_inhibition_compared_with_dual_blockade_in_lowering_proteinuria_and_blood_pressure:_randomised_controlled_trial_ L2 - https://www.bmj.com/lookup/pmidlookup?view=long&amp;pmid=21791491 DB - PRIME DP - Unbound Medicine ER -