Endothelin A receptor antagonists in diabetic kidney disease

Panagiotis I. Georgianos, Rajiv Agarwal

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations


Purpose of review Despite optimal therapy of diabetic nephropathy with agents blocking the renin-angiotensin-aldosterone system, the residual risk of nephropathy progression to end-stage renal disease (ESRD) remains high. The purpose of this review is to discuss the potential role of endothelin antagonism as a therapeutic tool to reduce residual proteinuria and delay kidney injury progression among patients with diabetic nephropathy. Recent findings Preclinical studies have shown that endothelin receptor antagonists (ERAs) exert proteinuria lowering and nephroprotective actions in experimental models of diabetic nephropathy. ERAs reduce proteinuria in phase 2 trials that included therapy with renin-angiotensin-aldosterone system blockers. Safety of these agents and protection from ESRD needs to be demonstrated in phase 3 trials. Excess risk of fluid retention and heart failure risk remains. Summary The hypothesis that the antiproteinuric effect of endothelin antagonism may be translated into a slower progression of diabetic nephropathy to ESRD is investigated in ongoing randomized trials assessing 'hard' renal endpoints. ERAs may represent a promising tool toward renoprotection in diabetic nephropathy by individualizing therapy and mitigating the risk of heart failure, if these trials are positive.

Original languageEnglish (US)
Pages (from-to)338-344
Number of pages7
JournalCurrent Opinion in Nephrology and Hypertension
Issue number5
StatePublished - Sep 1 2017


  • diabetic nephropathy
  • endothelin antagonism
  • kidney injury progression
  • proteinuria

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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