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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; 343 doi: https://doi.org/10.1136/bmj.d4366 (Published 26 July 2011) Cite this as: BMJ 2011;343:d4366
  1. Maartje C J Slagman, internist in training1,
  2. Femke Waanders, internist in training1,
  3. Marc H Hemmelder, internist in training2,
  4. Arend-Jan Woittiez, internist-nephrologist3,
  5. Wilbert M T Janssen, internist-nephrologist4,
  6. Hiddo J Lambers Heerspink, pharmacist5,
  7. Gerjan Navis, internist-nephrologist1,
  8. Gozewijn D Laverman, internist-nephrologist, HONEST coordinator13
  9. for the HONEST (HOlland NEphrology STudy) Group
  1. 1Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Netherlands
  2. 2Department of Internal Medicine, Division of Nephrology, Medical Center Leeuwarden, Netherlands
  3. 3Department of Internal Medicine, Division of Nephrology, ZGT Hospital Almelo, Netherlands
  4. 4Department of Internal Medicine, Division of Nephrology, Martini Hospital Groningen
  5. 5Department of Pharmacology, University Medical Center Groningen
  1. Correspondence: G D Laverman g.d.laverman{at}umcg.nl
  • Accepted 13 May 2011

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.

Footnotes

  • We thank Nynke Halbesma, epidemiologist at the department of internal medicine, division of nephrology, University Medical Center Groningen, for her help in the statistical analyses of the results. We also thank Folkert W Visser, Jan A Krikken, and Arjan Kwakernaak from the department of internal medicine, division of nephrology, University Medical Center Groningen for their help in collecting the data.

  • Contributors: MCJS and FW contributed equally. MCJS collected data, did the analyses, and wrote the manuscript. FW designed the study, collected data, and wrote the manuscript. MHH and A-JW facilitated the execution of the study and wrote the manuscript. WMTJ, HLH, and GDL contributed to the analyses and wrote the manuscript. GN designed the study, facilitated the execution of the study, contributed to the analyses, and wrote the manuscript. GDL is the guarantor.

  • Funding: The study was supported by an unrestricted grant from Novartis (CVAL489ANL08). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that GN has support from Novartis for the submitted work; none of the authors had a relationship with a company that might have an interest in the submitted work in the previous 3 years; and MCJS, FW, MHH, A-JW, WMTJ, HLH, and GDL have no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: The institutional ethics committee at each centre approved the protocol. All participants gave written informed consent.

  • Data sharing: No additional data available.

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