title: Circulating markers of endothelial dysfunction interact with proteinuria in predicting mortality in renal transplant recipients.
abstract: BACKGROUND
  Proteinuria is associated with endothelial dysfunction (ED) and increased mortality. We investigated whether urinary protein excretion (UPE) is correlated with markers of ED and whether these markers affect the association of proteinuria with mortality in renal transplant recipients (RTR).
  
  
  METHODS
  Six hundred four RTR with a functioning graft for more than 1 year were included. RTR were divided according to UPE: less than 0.3, 0.3 to 1.0, and more than 1.0 g/24 hr. Soluble intercellular adhesion molecule type 1 (sICAM-1) and soluble vascular cellular adhesion molecule type 1 (sVCAM-1) were measured using ELISA.
  
  
  RESULTS
  UPE (0.2 [0.0-0.5] g/24 hr), sICAM-1 (603 (514-721) ng/mL), and sVCAM-1 (952 [769-1196] ng/mL) were measured at 6.0 (2.6-11.4) years posttransplant. During follow-up for 5.3 (4.7-5.7) years, 94 (16%) RTR died. UPE was correlated with sVCAM-1 (standardized beta=0.13, P=0.001) but not with sICAM-1 (standardized beta=0.04, P=0.3). RTR with UPE more than 1.0 g/24 hr and high sICAM-1 (hazard ratio=4.7, 95% confidence interval 2.3-9.7, P<0.0001) or sVCAM-1 (hazard ratio=4.2, 95% confidence interval 2.0-8.6, P=0.0001) concentrations were at increased risk for death, whereas RTR with UPE more than 1.0 g/24 hr and low concentrations of sICAM-1 and sVCAM-1 were not.
  
  
  CONCLUSIONS
  In RTR, UPE is correlated with sVCAM-1 but not with sICAM-1. Furthermore, RTR with proteinuria and high concentrations of sICAM-1 or sVCAM-1 have an increased risk for death, compared with RTR without proteinuria, whereas this is not the case in RTR with proteinuria but low concentrations of sICAM-1 and sVCAM-1. These results suggest that ED plays a role in the association of proteinuria with mortality after renal transplantation.
authors.affiliation: The Renal Transplant Program, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. r.m.van.ree@int.umcg.nl
authors.forename: Rutger M
authors.initials: RM
authors.lastname: van Ree
authors.forename: Leendert H
authors.initials: LH
authors.lastname: Oterdoom
authors.forename: Aiko P J
authors.initials: AP
authors.lastname: de Vries
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Homan van der Heide
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Son
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Reinold O B
authors.initials: RO
authors.lastname: Gans
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood* / Q000652:urine; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016030:Kidney Transplantation / Q000401:mortality* / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000453:epidemiology / Q000503:physiopathology*; D012189:Retrospective Studies; D015996:Survival Rate; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D008055:Lipids; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1