Plasma concentrations of the vasoactive peptide fragments mid-regional pro-adrenomedullin, C-terminal pro-endothelin 1 and copeptin in hemodialysis patients

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Plasma concentrations of the vasoactive peptide fragments mid-regional pro-adrenomedullin, C-terminal pro-endothelin 1 and copeptin in hemodialysis patients : associated factors and prediction of mortality. / Artunc, Ferruh; Nowak, Albina; Mueller, Christian; Breidthardt, Tobias; Twerenbold, Raphael; Wagner, Robert; Peter, Andreas; Haering, Hans-Ulrich; Ebmeyer, Stefan; Friedrich, Bjoern.

in: PLOS ONE, Jahrgang 9, Nr. 1, 2014, S. e86148.

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@article{f7e3d31cea8544ba86f220ce270a0693,
title = "Plasma concentrations of the vasoactive peptide fragments mid-regional pro-adrenomedullin, C-terminal pro-endothelin 1 and copeptin in hemodialysis patients: associated factors and prediction of mortality",
abstract = "Vasopressin, endothelin and adrenomedullin are vasoactive peptides that regulate vascular tone and might play a role in hypertensive diseases. Recently, laboratory assays have been developed to measure stable fragments of vasopressin, endothelin and adrenomedullin. Little is known about their diagnostic and prognostic value in hemodialysis patients. In this study, we measured the plasma concentration of copeptin, mid-regional-pro-adrenomedullin (MR-pro-ADM) and C-terminal pro-endothelin 1 (CT-pro-ET1) in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors and mortality. In all patients enrolled, the plasma concentrations of copeptin, MR-pro-ADM and CT-pro-ET1 were largely elevated with a median concentration of 132 pmol/L (interquartile range [IQR] 78-192) for copeptin, 1.26 nmol/L (IQR 1.02-1.80) for MR-pro-ADM and 149 pmol/L (IQR 121-181) for CT-pro-ET1. The plasma concentrations of all vasoactive peptide fragments correlated with time on dialysis and plasma β2-microglobulin concentration and were negatively correlated to residual diuresis. The plasma concentration of MR-pro-ADM was a strong predictor of all-cause (univariate hazard ratio for a 10-fold increase 9.94 [3.14;32], p<0.0001) and cardiovascular mortality (hazard ratio 34.87 [5.58;217], p = 0.0001) within a 3.8-year follow-up. The associations remained stable in models adjusted for dialysis specific factors and were attenuated in a full model adjusted for all prognostic factors. Plasma copeptin concentration was weakly associated with cardiovascular mortality (only in univariate analysis) and CT-pro-ET1 was not associated with mortality at all. In conclusion, vasoactive peptide fragments are elevated in hemodialysis patients because of accumulation and, most likely, increased release. Increased concentrations of MR-pro-ADM are predictive of mortality.",
keywords = "Adrenomedullin/blood, Aged, Cause of Death, Comorbidity, Endothelin-1/blood, Female, Follow-Up Studies, Glycopeptides/blood, Humans, Kidney Diseases/blood, Male, Middle Aged, Peptide Fragments/blood, Prognosis, Prospective Studies, Protein Precursors/blood, Renal Dialysis",
author = "Ferruh Artunc and Albina Nowak and Christian Mueller and Tobias Breidthardt and Raphael Twerenbold and Robert Wagner and Andreas Peter and Hans-Ulrich Haering and Stefan Ebmeyer and Bjoern Friedrich",
year = "2014",
doi = "10.1371/journal.pone.0086148",
language = "English",
volume = "9",
pages = "e86148",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

RIS

TY - JOUR

T1 - Plasma concentrations of the vasoactive peptide fragments mid-regional pro-adrenomedullin, C-terminal pro-endothelin 1 and copeptin in hemodialysis patients

T2 - associated factors and prediction of mortality

AU - Artunc, Ferruh

AU - Nowak, Albina

AU - Mueller, Christian

AU - Breidthardt, Tobias

AU - Twerenbold, Raphael

AU - Wagner, Robert

AU - Peter, Andreas

AU - Haering, Hans-Ulrich

AU - Ebmeyer, Stefan

AU - Friedrich, Bjoern

PY - 2014

Y1 - 2014

N2 - Vasopressin, endothelin and adrenomedullin are vasoactive peptides that regulate vascular tone and might play a role in hypertensive diseases. Recently, laboratory assays have been developed to measure stable fragments of vasopressin, endothelin and adrenomedullin. Little is known about their diagnostic and prognostic value in hemodialysis patients. In this study, we measured the plasma concentration of copeptin, mid-regional-pro-adrenomedullin (MR-pro-ADM) and C-terminal pro-endothelin 1 (CT-pro-ET1) in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors and mortality. In all patients enrolled, the plasma concentrations of copeptin, MR-pro-ADM and CT-pro-ET1 were largely elevated with a median concentration of 132 pmol/L (interquartile range [IQR] 78-192) for copeptin, 1.26 nmol/L (IQR 1.02-1.80) for MR-pro-ADM and 149 pmol/L (IQR 121-181) for CT-pro-ET1. The plasma concentrations of all vasoactive peptide fragments correlated with time on dialysis and plasma β2-microglobulin concentration and were negatively correlated to residual diuresis. The plasma concentration of MR-pro-ADM was a strong predictor of all-cause (univariate hazard ratio for a 10-fold increase 9.94 [3.14;32], p<0.0001) and cardiovascular mortality (hazard ratio 34.87 [5.58;217], p = 0.0001) within a 3.8-year follow-up. The associations remained stable in models adjusted for dialysis specific factors and were attenuated in a full model adjusted for all prognostic factors. Plasma copeptin concentration was weakly associated with cardiovascular mortality (only in univariate analysis) and CT-pro-ET1 was not associated with mortality at all. In conclusion, vasoactive peptide fragments are elevated in hemodialysis patients because of accumulation and, most likely, increased release. Increased concentrations of MR-pro-ADM are predictive of mortality.

AB - Vasopressin, endothelin and adrenomedullin are vasoactive peptides that regulate vascular tone and might play a role in hypertensive diseases. Recently, laboratory assays have been developed to measure stable fragments of vasopressin, endothelin and adrenomedullin. Little is known about their diagnostic and prognostic value in hemodialysis patients. In this study, we measured the plasma concentration of copeptin, mid-regional-pro-adrenomedullin (MR-pro-ADM) and C-terminal pro-endothelin 1 (CT-pro-ET1) in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors and mortality. In all patients enrolled, the plasma concentrations of copeptin, MR-pro-ADM and CT-pro-ET1 were largely elevated with a median concentration of 132 pmol/L (interquartile range [IQR] 78-192) for copeptin, 1.26 nmol/L (IQR 1.02-1.80) for MR-pro-ADM and 149 pmol/L (IQR 121-181) for CT-pro-ET1. The plasma concentrations of all vasoactive peptide fragments correlated with time on dialysis and plasma β2-microglobulin concentration and were negatively correlated to residual diuresis. The plasma concentration of MR-pro-ADM was a strong predictor of all-cause (univariate hazard ratio for a 10-fold increase 9.94 [3.14;32], p<0.0001) and cardiovascular mortality (hazard ratio 34.87 [5.58;217], p = 0.0001) within a 3.8-year follow-up. The associations remained stable in models adjusted for dialysis specific factors and were attenuated in a full model adjusted for all prognostic factors. Plasma copeptin concentration was weakly associated with cardiovascular mortality (only in univariate analysis) and CT-pro-ET1 was not associated with mortality at all. In conclusion, vasoactive peptide fragments are elevated in hemodialysis patients because of accumulation and, most likely, increased release. Increased concentrations of MR-pro-ADM are predictive of mortality.

KW - Adrenomedullin/blood

KW - Aged

KW - Cause of Death

KW - Comorbidity

KW - Endothelin-1/blood

KW - Female

KW - Follow-Up Studies

KW - Glycopeptides/blood

KW - Humans

KW - Kidney Diseases/blood

KW - Male

KW - Middle Aged

KW - Peptide Fragments/blood

KW - Prognosis

KW - Prospective Studies

KW - Protein Precursors/blood

KW - Renal Dialysis

U2 - 10.1371/journal.pone.0086148

DO - 10.1371/journal.pone.0086148

M3 - SCORING: Journal article

C2 - 24465926

VL - 9

SP - e86148

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 1

ER -