title: Serum accumulation of a creatinine oxidative metabolite (NZ-419: 5-hydroxy-1- methylhydatoin) as an intrinsic antioxidant in diabetic patients with or without chronic kidney disease.
abstract: OBJECTIVE
  In mammals, creatinine (Cr) is catabolized by a dual oxidative pathway via 5-hydroxy-1-methylhydantoin or 5-hydroxycreatinine. The former, an intrinsic antioxidant, termed NZ-419, has been reported to prevent the progression of chronic renal failure in animal models. However, its clinical intrinsic serum level has not yet been reported.
  
  
  METHODS
  We analyzed serum NZ-419 levels in diabetic and nondiabetic patients with or without Stage 3 - 5 chronic kidney disease (CKD).
  
  
  RESULTS
  The levels of NZ-419 in diabetic patients with (88.1 ± 17.2 µg/dl, p < 0.001) or without (31.5 ± 2.4 µg/dl, p < 0.05) Stage 3 - 5 CKD were significantly higher than in nondiabetic normal controls (9.0 ± 5.6 µg/dl). The molar ratio data showed NZ-419/Cr was significantly higher in both diabetic patients with (p < 0.01) or without Stage 3 - 5 CKD (p < 0.001) compared to nondiabetic normal controls. No further increase occurred with increasing severity of renal failure. Furthermore, nondiabetic patients with or without Stage 3 - 5 CKD did not show significantly different molar ratio values than controls but had significantly higher values of NZ-419 levels (p < 0.001).
  
  
  CONCLUSIONS
  Overproduction and decreased clearance played a major role in the increased NZ-419 levels we observed in the patients with diabetes and Stage 3 - 5 CKD, respectively. The existence of chronic renal failure did not further enhance this overproduction.
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Yamashiro Country Hospital, Kyoto, Osaka, Japan. goji@koto.kpu-m.ac.jp
authors.forename: G
authors.initials: G
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Ienaga
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000097:blood*; D005260:Female; D006801:Humans; D006827:Hydantoins / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D000975:Antioxidants; D006827:Hydantoins; C058007:5-hydroxy-1-methylhydantoin; D003404:Creatinine