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.
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.
Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany.
Ferruh
F
Artunc
Division of Internal Medicine, Division of Nephrology, University of Zurich, Zurich, Switzerland.
Albina
A
Nowak
Department of Internal Medicine, Division of Cardiology, University of Basel, Basel, Switzerland.
Christian
C
Mueller
Department of Internal Medicine, Division of Cardiology, University of Basel, Basel, Switzerland.
Tobias
T
Breidthardt
Department of Internal Medicine, Division of Cardiology, University of Basel, Basel, Switzerland.
Raphael
R
Twerenbold
Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany.
Robert
R
Wagner
Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany.
Andreas
A
Peter
Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany.
Hans-Ulrich
HU
Haering
Fisher Scientific, Schwerte, Germany.
Stefan
S
Ebmeyer
Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany ; Dialysis Center, Leonberg, Germany.
Bjoern
B
Friedrich
D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D002423:Cause of Death; D015897:Comorbidity; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D006435:Renal Dialysis
C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D006020:Glycopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C048197:copeptins; C574167:mid-regional pro-adrenomedullin, human; D053607:Adrenomedullin