Evidence map›Paper›PMID 25801761›Full record

Trial reportJournal of the American Heart Association2015

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

Registry-linked trialOpen access · goldAbstract readObservational StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00810732 (THE EFFECTS OF SITAXSENTAN ONCE DAILY DOSING ON PROTEINURIA, 24-HOUR BLOOD PRESSURE, AND ARTERIAL STIFFNESS IN SUBJECTS WITH CHRONIC KIDNEY DISEASE), which is not on this map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00810732 phase2completednot on this map

The effects of sitaxsentan once daily dosing on proteinuria, 24-hour blood pressure, and arterial stiffness in subjects with chronic kidney disease

TypeinterventionalSponsorPfizerRan2007 to 2009Enrolled27ConditionsChronic Kidney DiseaseArmsOpen, Nifedipine, Placebo
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023
    Article
  8. Article
  9. Cardiovascular Biomarkers: Lessons of the Past and Prospects for the Future.International journal of molecular sciences · 2022
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Neeraj DhaunBHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK (N.D., R.A.K., P.C., I.M.M.I., D.J.W.) Department of Renal Medicine, Royal Infirmary of Edinburgh, UK (N.D., J.G.).
Jale YuzugulenWilliam Harvey Research Institute, Barts & the London School of Medicine, Queen Mary University of London, UK (J.Y., E.G.W., R.C.).
Robert A KimmittBHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK (N.D., R.A.K., P.C., I.M.M.I., D.J.W.).
Elizabeth G WoodWilliam Harvey Research Institute, Barts & the London School of Medicine, Queen Mary University of London, UK (J.Y., E.G.W., R.C.).
Pajaree ChariyavilaskulBHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK (N.D., R.A.K., P.C., I.M.M.I., D.J.W.).
Iain M MacIntyreBHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK (N.D., R.A.K., P.C., I.M.M.I., D.J.W.).
Jane GoddardDepartment of Renal Medicine, Royal Infirmary of Edinburgh, UK (N.D., J.G.).
David J WebbBHF Centre of Research Excellence, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK (N.D., R.A.K., P.C., I.M.M.I., D.J.W.).
Roger CorderWilliam Harvey Research Institute, Barts & the London School of Medicine, Queen Mary University of London, UK (J.Y., E.G.W., R.C.).
The Queen's Medical Research Institute · GBQueen Mary University of London · GBUniversity of Edinburgh · GBEdinburgh Royal Infirmary · GBWilliam Harvey Research Institute · GB

Funding

British Heart Foundation FS/13/30/29994British Heart Foundation PG/05/91Medical Research Council G0801509
6 · The paper itself

Abstract

backgroundEndothelin 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

resultsWe 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<0.0001). Following intervention, placebo and nifedipine did not affect plasma and urine ELDP or plasma CT-proET-1. Sitaxentan increased both plasma ELDP and CT-proET-1 (baseline versus week 6±SEM: ELDP, 11.8±0.5 versus 13.4±0.6 fmol/mL; CT-proET-1, 20.5±1.2 versus 23.3±1.5 fmol/mL; both P<0.0001). Plasma ET-1 was unaffected by any treatment. Following sitaxentan, plasma ELDP and CT-proET-1 correlated negatively with 24-hour urinary sodium excretion.

conclusionsELDP 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. CLINICAL

trial registrationURL: www.clinicalTrials.gov Unique identifier: NCT00810732.

Indexed as

AdultBiomarkersBlood PressureCalcium Channel BlockersCross-Over StudiesDouble-Blind MethodEndothelin-1Endothelin A Receptor AntagonistsFemaleHumansIsoxazolesMaleMiddle AgedNifedipineProtein PrecursorsProteinuriaBiomarkersCalcium Channel BlockersEndothelin-1Endothelin A Receptor AntagonistsIsoxazolesNifedipineproendothelin 1Protein PrecursorsReceptor, Endothelin AsitaxsentanThiophenesantagonistsCKDendothelinfluid retention

Identifiers

PMID25801761
PMCPMC4392442
OpenAlexW2132578714

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.