Ping Li1,2, Insa M Schmidt1,3, Venkata Sabbisetti1, Maria Clarissa Tio1, Alexander R Opotowsky4,5, Sushrut S Waikar6,3. 1. Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 2. Department of Nephrology, State Key Laboratory of Kidney Disease, National Clinical Research Center for Kidney Disease, Chinese PLA General Hospital, Beijing, China. 3. Boston University Medical Center, Boston, Massachusetts. 4. Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 5. Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts. 6. Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts swaikar@bu.edu.
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. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_05_15_CJN11130919.mp3.
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. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_05_15_CJN11130919.mp3.
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