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Improving the efficacy of RAAS blockade in patients with chronic kidney disease

Nature Reviews Nephrology volume 9, pages 112–121 (2013)Cite this article

Abstract

Reduction of blood pressure and proteinuria by blockade of the renin–angiotensin–aldosterone system (RAAS) has been the cornerstone of renoprotective intervention for patients with chronic kidney disease (CKD) for many years. Despite the proven efficacy of RAAS blockade, however, the reduction in proteinuria is insufficient in many patients, and does not prevent further deterioration of renal function. Short-term studies have shown that a variety of treatment intensification strategies have a beneficial effect on blood pressure and proteinuria, including RAAS blockade using either dose escalation or multiple drugs, and restriction of dietary sodium. Large clinical trials have shown that RAAS blockade with multiple drugs does not improve patients' long-term renal or cardiovascular outcome. By contrast, two post-hoc analyses of landmark trials in nephrology show beneficial renal and cardiovascular effects from avoiding excessive dietary sodium intake during single-agent RAAS blockade therapy. The effects of dietary sodium restriction on renal or cardiovascular outcome still require prospective confirmation. However, current data support the implementation of lifestyle changes to reduce dietary sodium intake in combination with single-agent RAAS blockade, rather than dual-agent RAAS blockade, as a potent and feasible strategy to mitigate the burden of renal and cardiovascular disease in patients with CKD.

Key Points

  • Despite the proven efficacy of blockade of the renin–angiontensin–aldosterone system (RAAS) as a treatment for chronic kidney disease the prognosis of these patients is poor

  • Recent data from large clinical trials demonstrate that a combination of two drugs that block the RAAS does not protect patients against renal and cardiovascular outcomes

  • Avoidance of excessive dietary sodium intake has been shown to enhance the effect of single-agent RAAS blockade against renal and cardiovascular outcomes in two post-hoc analyses of clinical trials

  • Lifestyle changes to avoid high dietary sodium intake are advised with RAAS blockade to reduce the risk of renal and cardiovascular outcomes in patients with chronic kidney disease

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Figure 1: The relationship between sodium status and adverse event rates during RAAS blockade.
Figure 2: The relationship between sodium status and all-cause mortality during RAAS blockade.
Figure 3: The effect of NT-proBNP levels on the response of patients with chronic kidney disease to the angiotensin-receptor blocker losartan.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 9700 AD, Groningen, The Netherlands

    Hiddo J. Lambers Heerspink

  2. Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 9700 AD, Groningen, The Netherlands

    Martin H. de Borst, Stephan J. L. Bakker & Gerjan J. Navis

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H. J. Lambers Heerspink and G. J. Navis wrote the article. H. J. Lambers Heerspink, M. H. de Borst, S. J. L. Bakker and G. J. Navis contributed to discussion of the content. M. H. de Borst and S. J. L. Bakker contributed to review and/or editing of the manuscript before submission.

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Correspondence to Gerjan J. Navis.

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Lambers Heerspink, H., de Borst, M., Bakker, S. et al. Improving the efficacy of RAAS blockade in patients with chronic kidney disease. Nat Rev Nephrol 9, 112–121 (2013). https://doi.org/10.1038/nrneph.2012.281

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