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Original ArticlesMaintenance Dialysis
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Plasma Endothelin-1 and Risk of Death and Hospitalization in Patients Undergoing Maintenance Hemodialysis

Ping Li, Insa M. Schmidt, Venkata Sabbisetti, Maria Clarissa Tio, Alexander R. Opotowsky and Sushrut S. Waikar
CJASN June 2020, 15 (6) 784-793; DOI: https://doi.org/10.2215/CJN.11130919
Ping Li
1Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
2Department of Nephrology, State Key Laboratory of Kidney Disease, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital, Beijing, China
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Insa M. Schmidt
1Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
3Boston University Medical Center, Boston, Massachusetts
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Venkata Sabbisetti
1Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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Maria Clarissa Tio
1Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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Alexander R. Opotowsky
4Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
5Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts
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Sushrut S. Waikar
1Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
3Boston University Medical Center, Boston, Massachusetts
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Abstract

Background and objectives Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide implicated in the pathogenesis of hypertension, congestive heart failure, and inflammation, all of which are critical pathophysiologic features of CKD.

Design, setting, participants, & measurements To test the hypothesis that plasma endothelin-1 levels are associated with increased risks of mortality and hospitalization in patients with chronic kidney failure, we measured plasma endothelin-1 levels in a prospective cohort of 794 individuals receiving maintenance hemodialysis. The primary outcomes were time to death and time to hospitalization.

Results The median plasma endothelin-1 level was 2.02 (interquartile range, 1.57–2.71) pg/ml. During a median follow-up period of 28 (interquartile range, 21–29) months, 253 individuals (32%) died and 643 individuals (81%) were hospitalized at least once. In multivariable models adjusted for demographic, clinical, and laboratory variables, individuals in the highest quartile of plasma endothelin-1 had a 2.44-fold higher risk of death (hazard ratio, 2.44; 95% confidence interval, 1.61 to 3.70) and a 1.54-fold higher risk of hospitalization (hazard ratio, 1.54; 95% confidence interval, 1.19 to 1.99) compared with individuals in the lowest quartile. The Harrell C-statistic of the fully adjusted model increased from 0.73 to 0.74 after addition of natural log-transformed plasma endothelin-1 (P<0.001) for all-cause mortality, and increased from 0.608 to 0.614 after addition of natural log-transformed plasma endothelin-1 (P=0.002) for hospitalization.

Conclusions Higher plasma endothelin-1 is associated with adverse clinical events in patients receiving hemodialysis independent of previously described risk factors.

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  • Endothelin-1
  • hemodialysis
  • mortality
  • cardiovascular disease
  • risk factors
  • Prospective Studies
  • Kidney Failure
  • Chronic
  • dialysis
  • Endothelins
  • Renal Insufficiency
  • Chronic
  • Vasoconstrictor Agents
  • hospitalization
  • heart failure
  • hypertension
  • endothelium
  • Inflammation
  • Cohort Studies
  • Received September 6, 2019.
  • Accepted March 19, 2020.
  • Copyright © 2020 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 15 (6)
Clinical Journal of the American Society of Nephrology
Vol. 15, Issue 6
June 08, 2020
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Plasma Endothelin-1 and Risk of Death and Hospitalization in Patients Undergoing Maintenance Hemodialysis
Ping Li, Insa M. Schmidt, Venkata Sabbisetti, Maria Clarissa Tio, Alexander R. Opotowsky, Sushrut S. Waikar
CJASN Jun 2020, 15 (6) 784-793; DOI: 10.2215/CJN.11130919

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Plasma Endothelin-1 and Risk of Death and Hospitalization in Patients Undergoing Maintenance Hemodialysis
Ping Li, Insa M. Schmidt, Venkata Sabbisetti, Maria Clarissa Tio, Alexander R. Opotowsky, Sushrut S. Waikar
CJASN Jun 2020, 15 (6) 784-793; DOI: 10.2215/CJN.11130919
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Keywords

  • Endothelin-1
  • hemodialysis
  • mortality
  • cardiovascular disease
  • risk factors
  • Prospective Studies
  • kidney failure
  • Chronic
  • dialysis
  • Endothelins
  • renal insufficiency
  • Vasoconstrictor Agents
  • hospitalization
  • heart failure
  • hypertension
  • endothelium
  • inflammation
  • Cohort Studies

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