title: Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease.
abstract: BACKGROUND
  Endothelial dysfunction (ED) is a key event in the development of atherosclerotic cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Association of hyperuricemia with CVD has been previously reported in the nonuremic population. In this prospective study, we aimed to evaluate the effects of treatment of hyperuricemia with allopurinol on ED and changes in the serum reactive oxygen species in patients with CKD.
  
  
  METHODS
  In this study, 19 (13 male) hyperuricemic (UA > 7 mg/dl) nondiabetic CKD patients without any comorbidity, aged < 60 years with creatinine clearance (CrCl) between 20 and 60 ml/min were evaluated. Endothelial functions were assessed by ischemia-induced forearm vasodilatation method (EDD). Oxidative stress was evaluated by measuring the serum oxidized LDL (ox-LDL), advanced oxidation protein products (AOPP) and nitrotyrosine (NT) levels. After measuring all these tests at baseline, allopurinol therapy was commenced for 8 weeks. After 8 weeks of allopurinol treatment, all measurements were repeated. Then, allopurinol treatment was ceased and same measurements were also repeated 8 weeks after ceasing of the treatment.
  
  
  RESULTS
  Serum creatinine, total cholesterol, albumin, hs-CRP, CrCl and proteinuria levels of the patients were similar among three study periods. After allopurinol therapy, the mean serum UA and NT levels significantly reduced as compared to baseline. At the 8th week after cessation of allopurinol treatment, serum UA levels were significantly increased. After allopurinol therapy, EDD value increased from 5.42 ± 8.3% at baseline to 11.37 ± 9% (p < 0.001). At the 8th week after ceasing allopurinol treatment, EDD returned to baseline values (5.96 ± 8%, p < 0.001).
  
  
  CONCLUSIONS
  Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol.
authors.affiliation: Department of Internal Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Yelken
authors.forename: Yasar
authors.initials: Y
authors.lastname: Caliskan
authors.forename: Numan
authors.initials: N
authors.lastname: Gorgulu
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Altun
authors.forename: Akar
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Halil
authors.initials: H
authors.lastname: Yazici
authors.forename: Huseyin
authors.initials: H
authors.lastname: Oflaz
authors.forename: Alaattin
authors.initials: A
authors.lastname: Yildiz
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood; D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000378:metabolism; D000465:Algorithms; D000493:Allopurinol / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014528:Uricosuric Agents / Q000627:therapeutic use*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000418:Albumins; D015415:Biomarkers; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D014528:Uricosuric Agents; C099252:oxidized low density lipoprotein; C002744:3-nitrotyrosine; D014443:Tyrosine; D000493:Allopurinol; D002097:C-Reactive Protein; D003404:Creatinine