Plasma Pro-Endothelin-1 Peptide Concentrations Rise in Chronic Kidney Disease and Following Selective Endothelin A Receptor Antagonism

Neeraj Dhaun, Jale Yuzugulen, Robert A. Kimmitt, Elizabeth G. Wood, Pajaree Chariyavilaskul, Iain M. MacIntyre, Jane Goddard, David J. Webb, Roger Corder

Research output: Contribution to journalArticlepeer-review

Abstract

Background Endothelin 1 (ET-1) contributes to chronic kidney disease (CKD) development and progression, and endothelin receptor antagonists are being investigated as a novel therapy for CKD. The proET-1 peptides, endothelin-like domain peptide (ELDP) and C-terminal pro-ET-1 (CT-proET-1), are both potential biomarkers of CKD and response to therapy with endothelin antagonists.

Methods and Results We assessed plasma and urine ELDP and plasma CT-proET-1 in CKD patients with minimal comorbidity. Next, in a randomized double-blind crossover study of 27 subjects with proteinuric CKD, we examined the effects of 6 weeks of treatment with placebo, sitaxentan (endothelin A antagonist), and nifedipine on these peptides alongside the primary end points of proteinuria, blood pressure, and arterial stiffness. Plasma ELDP and CT-proET-1 increased with CKD stage (both P---0.0001), correlating inversely with estimated glomerular filtration rate (both P

Conclusions ELDP and CT-proET-1 increase in CKD and thus are potentially useful biomarkers of renal injury. Increases in response to endothelin A antagonism may reflect EDN1 upregulation, which may partly explain fluid retention with these agents.

Original languageEnglish
Article number001624
Number of pages10
JournalJournal of the American Heart Association Cardiovascular and Cerebrovascular Disease
Volume4
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • antagonists
  • CIO
  • endothelin
  • fluid retention
  • CARDIOVASCULAR-DISEASE
  • PULMONARY-HYPERTENSION
  • METABOLIC SYNDROME
  • BLOOD-PRESSURE
  • RENAL-DISEASE
  • PREDICTION
  • BIOMARKERS
  • CLEARANCE
  • MARKER
  • CELLS

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