Use of Renin-Angiotensin System Blockade in Advanced CKD: An NKF-KDOQI Controversies Report

Am J Kidney Dis. 2018 Dec;72(6):873-884. doi: 10.1053/j.ajkd.2018.06.010. Epub 2018 Sep 7.


Multiple clinical trials have demonstrated that renin-angiotensin system (RAS) blockade with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers effectively reduces chronic kidney disease (CKD) progression. However, most clinical trials excluded participants with advanced CKD (ie, estimated glomerular filtration rate [eGFR]<30mL/min/1.73m2). It is acknowledged that initiation of RAS blockade is often associated with an acute reduction in eGFR, which is thought to be functional, but may result in long-term preservation of kidney function through the reductions in glomerular intracapillary pressure conferred by these agents. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) report, we discuss the controversies regarding use of RAS blockade in patients with advanced kidney disease. We review available published data on this topic and provide perspective on the impact of RAS blockade on changes in eGFRs and potassium levels. We conclude that more research is needed to evaluate the therapeutic index of RAS blockade in patients with advanced CKD.

Keywords: RAAS blockade; Renin angiotensin aldosterone system (RAAS); advanced CKD; angiotensin II receptor blockers (ARBs); angiotensin converting enzyme inhibitors (ACEi); blood pressure; cardiovascular risk; chronic kidney disease (CKD); diabetes; drug safety; end-stage renal disease (ESRD); estimated glomerular filtration rate (eGFR); hypertension; mortality; proteinuria; reduced eGFR; renal disease progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Disease Progression
  • Evidence-Based Medicine
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Male
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / pathology*
  • Renal Insufficiency, Chronic / physiopathology
  • Renin-Angiotensin System / drug effects*
  • Risk Assessment
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome
  • United States


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors