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

Nat Rev Nephrol. 2013 Feb;9(2):112-21. doi: 10.1038/nrneph.2012.281. Epub 2012 Dec 18.


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.

Publication types

  • Review

MeSH terms

  • Glyceraldehyde-3-Phosphate Dehydrogenases / therapeutic use
  • Humans
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Peptide Fragments / therapeutic use
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology*
  • Renin / antagonists & inhibitors
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology*
  • Sodium Chloride, Dietary


  • Mineralocorticoid Receptor Antagonists
  • Peptide Fragments
  • Sodium Chloride, Dietary
  • glyceraldehyde 3-phosphate dehydrogenase (304-313)
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Renin