title: Osteoprotegerin as a predictor of renal and cardiovascular outcomes in renal transplant recipients: follow-up data from the ALERT study.
abstract: BACKGROUND
  In patients with chronic kidney disease, vascular calcification contributes to increased cardiovascular (CV) morbidity and mortality. CV risk remains high after successful renal transplantation. Osteoprotegerin (OPG) is a glycoprotein, involved in the regulation of the vascular calcification process. Previous studies have shown that elevated OPG is predictive of mortality in high-risk populations. The aim of this study was to investigate the prognostic value of OPG for graft function, CV events and all-cause death, in a large transplant cohort.
  
  
  METHODS
  OPG was measured at baseline in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) study, a randomized placebo-controlled intervention study comparing fluvastatin and placebo. Patients were followed for 6.7 years with evaluation of pre-specified end points, graft loss, graft function, CV events and death.
  
  
  RESULTS
  OPG was analysed in 1889 renal transplant recipients, with a mean value of 4.69 ± 1.85 pg/L. The number of renal and CV events increased by quartiles of OPG. In the multivariate analysis, OPG in the fourth as compared to first quartile was an independent predictor of graft failure or doubling of serum creatinine [hazard ratio (HR) 2.20 (1.56-3.11), P < 0.001], major CV events [HR 2.40 (1.58-3.64), P < 0.001], cardiac mortality [HR 2.80 (1.32-5.94), P = 0.007] and all-cause mortality [HR 2.31 (1.53-3.49), P < 0.001].
  
  
  CONCLUSIONS
  In a large cohort of kidney transplant patients with long-term follow-up, OPG was independently associated with renal events, CV events and mortality.
authors.affiliation: Department of Nephrology, Aarhus University Hospital, Aarhus, Denmark. mys@dadlnet.dk
authors.forename: My
authors.initials: M
authors.lastname: Svensson
authors.forename: Dag Olav
authors.initials: DO
authors.lastname: Dahle
authors.forename: Geir
authors.initials: G
authors.lastname: Mjøen
authors.forename: Gisela
authors.initials: G
authors.lastname: Weihrauch
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Alan
authors.initials: A
authors.lastname: Jardine
authors.forename: Bengt
authors.initials: B
authors.lastname: Fellström
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality*; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000378:metabolism*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D061205:Vascular Calcification / Q000175:diagnosis / Q000209:etiology / Q000401:mortality
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D053244:Osteoprotegerin; D000077340:Fluvastatin; D003404:Creatinine