title: Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease.
abstract: In this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease.
  
  
  
  We studied a cohort of young and otherwise healthy ADPKD patients (n = 235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up.
  
  
  
  At baseline, median eGFR was 69 mL/min./1.73 m2, mean FMD 6.9 ± 0.9%, cIMT 0.7 ± 0.1 mm, and PWV 8.1 ± 1.2 m/s. At follow-up, equivalent values were 65 (44-75) mL/min./1.73 m2, 5.8 ± 0.9%, 0.8 ± 0.1 mm. and 8.2 ± 1.3 m/s. with all changes statistically significant. Plasma copeptin also rose from 0.62 ± 0.12 to 0.94 ± 0.19 ng/mL and this change correlated with ΔeGFR (-0.33, p < 0.001), ΔFMD (0.599, p < 0.001), ΔcIMT (0.562, p < 0.001) and ΔPWV (0.27, p < 0.001) also after linear regression modeling to correct for confounders. Finally, ROC analysis was done for a high baseline copeptin with ΔeGFR [cut-off:≤59], ΔFMD [cut-off: ≤7.08], ΔcIMT [cut-off:>0.76], and ΔPWV [cut-off:≤7.80].
  
  
  
  Vascular dysfunction as reflected by FMD and cIMT, but not PWV or an altered cardiac geometry, precede most other signs of disease in ADPKD but is predicted by elevated levels of the circulating AVP-marker copeptin.
authors.affiliation: Department of Nephrology, Erciyes University Medical Faculty, Kayser, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Kocyigit
authors.affiliation: Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.affiliation: Department of Nephrology, KahramanMaras Sutcu Imam University, Kahramanmaras, Turkey.
authors.forename: Ozkan
authors.initials: O
authors.lastname: Gungor
authors.affiliation: Department of Nephrology, Erciyes University Medical Faculty, Kayser, Turkey.
authors.forename: Eray
authors.initials: E
authors.lastname: Eroglu
authors.affiliation: Department of Nephrology, Erciyes University Medical Faculty, Kayser, Turkey.
authors.forename: Aydin
authors.initials: A
authors.lastname: Unal
authors.affiliation: Department of Cardiology, Mersin University Medical Faculty, Mersin, Turkey.
authors.forename: Ozcan
authors.initials: O
authors.lastname: Orscelik
authors.affiliation: Department of Nephrology, Erciyes University Medical Faculty, Kayser, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Tokgoz
authors.affiliation: Department of Nephrology, Erciyes University Medical Faculty, Kayser, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Sipahioglu
authors.affiliation: Department of Biochemistry, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Sen
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Carrero
authors.affiliation: Department of Nephrology, Erciyes University Medical Faculty, Kayser, Turkey.
authors.forename: Oktay
authors.initials: O
authors.lastname: Oymak
authors.affiliation: Vascular Biology Group, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. jonas.axelsson@karolinska.se.|Department of Clinical Immunology, C2:66, Karolinska University Hospital, 14186, Stockholm, Sweden. jonas.axelsson@karolinska.se.
authors.forename: Jonas
authors.identifier: 0000-0002-7377-9356
authors.initials: J
authors.lastname: Axelsson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D059168:Carotid Intima-Media Thickness; D004452:Echocardiography; D004727:Endothelium / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006020:Glycopeptides / Q000097:blood*; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D007690:Polycystic Kidney Diseases / Q000097:blood* / Q000503:physiopathology; D063177:Pulse Wave Analysis; D013318:Stroke Volume; D014664:Vasodilation; D014667:Vasopressins / Q000502:physiology
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; C048197:copeptins; D014667:Vasopressins
keywords: AVP; Arterial dysfunction; CVD risk; Endothelial dysfunction; Hereditary