title: Plasma Xanthine Oxidase Activity Is Predictive of Cardiovascular Disease in Patients with Chronic Kidney Disease, Independently of Uric Acid Levels.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Oxidative stress seems to play a pivotal role in this process, and purine metabolism may be involved in CKD-related oxidative stress. Xanthine oxidase (XO) is an enzyme involved in purine metabolism and is also responsible for the production of reactive oxygen species.
  
  
  METHODS
  This prospective study aimed to analyze the relation between plasma dosages of molecules involved in redox balance, purine metabolism and cardiovascular events in patients with non-diabetic CKD stages 3-5 or on chronic hemodialysis (HD). CKD (n = 51) and HD (n = 50) patients were compared to matched healthy controls (n = 38) and followed-up for 3 years.
  
  
  RESULTS
  Both CKD and HD patients had decreased plasma levels of antioxidants (selenium, zinc, vitamin C). HD patients had decreased levels of the antioxidant enzyme superoxide dismutase and increased levels of oxidation products (ischemia-modified albumin, malondialdehyde [MDA]). The following substrates and enzymes involved in purine metabolism were increased in the HD cohort: adenosine, adenosine deaminase and the pro-oxidant XO. XO activity was negatively correlated with super oxide dismutase and positively with MDA. Interestingly, XO activity was an independent predictor of cardiovascular events in CKD and HD patients, regardless of uric acid levels. Uric acid was not predictive of events.
  
  
  CONCLUSIONS
  This highlights a possible role of XO itself in CKD-related cardiovascular disease (CVD) and raises the hypothesis that beneficial effects observed with XO inhibitors on CVD in CKD may also be due to the reduction of oxidative stress.
authors.affiliation: Centre de Nephrologie et Transplantation Rx00E9;nale, Hopital La Conception, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Gondouin
authors.forename: Noemie
authors.initials: N
authors.lastname: Jourde-Chiche
authors.forename: Marion
authors.initials: M
authors.lastname: Sallee
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dou
authors.forename: Claire
authors.initials: C
authors.lastname: Cerini
authors.forename: Anderson
authors.initials: A
authors.lastname: Loundou
authors.forename: Sophie
authors.initials: S
authors.lastname: Morange
authors.forename: Yvon
authors.initials: Y
authors.lastname: Berland
authors.forename: Stephane
authors.initials: S
authors.lastname: Burtey
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunet
authors.forename: Regis
authors.initials: R
authors.lastname: Guieu
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dussol
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011687:Purines / Q000378:metabolism; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications* / Q000401:mortality; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D014969:Xanthine Oxidase / Q000097:blood*
chemical_list: D011687:Purines; D014527:Uric Acid; D014969:Xanthine Oxidase