title: Origin and characteristics of an unusual pyridine nucleotide accumulating in erythrocytes: positive correlation with degree of renal failure.
abstract: BACKGROUND
  Our aim was to identify an unusual nucleotide accumulating, with precursors, in erythrocytes in uraemia and to establish its relationship to the candidate uraemic toxin, N1-methyl-2-pyridone-5-carboxamide (M2Py).
  
  
  METHODS
  This nucleotide, plasma creatinine and M2Py were measured in four categories of patients: mild chronic renal failure (CRF), end-stage renal failure (ESRF), haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD); also in healthy controls and patients after successful kidney transplantation (Post-Tx).
  
  
  RESULTS
  The nucleotide was identified using liquid chromatography and mass spectrometry as 2-pyridone-5-carboxamide ribonucleoside triphosphate (2PyTP). In the patient groups, mean 2PyTP concentrations are lowest in CRF (21.8 micromol/l), increasing with degree of renal failure through ESRF (55.1 micromol/l) and HD patients (70.9 micromol/l) and being highest in CAPD patients (216.7 micromol/l). Following successful transplantation, 2PyTP concentrations fall to the control range. Plasma concentrations of M2Py correlate with 2PyTP in the erythrocytes; both are undetectable in patients lacking molybdenum cofactor, needed to oxidise N-methylnicotinamide.
  
  
  CONCLUSIONS
  Our evidence indicates that M2Py accumulates in parallel with the nucleotide 2PyTP in renal failure: either may be a uraemic toxin, since both increase with the degree of renal failure. Elevated concentrations of 2PyTP in CAPD patients reflect a longer half-life for erythrocytes than in HD patients.
authors.affiliation: Purine Research Unit, Guy's Hospital, 5th Floor, Thomas Guy House, London SE1 9RT, UK. elizabeth.carrey@kcl.ac.uk
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Carrey
authors.forename: Ryszard T
authors.initials: RT
authors.lastname: Smolenski
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Edbury
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Marinaki
authors.forename: John A
authors.initials: JA
authors.lastname: Duley
authors.forename: Limin
authors.initials: L
authors.lastname: Zhu
authors.forename: David J A
authors.initials: DJ
authors.lastname: Goldsmith
authors.forename: H Anne
authors.initials: HA
authors.lastname: Simmonds
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D016030:Kidney Transplantation; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood*; D009711:Nucleotides / Q000096:biosynthesis / Q000097:blood*; D051437:Renal Insufficiency / Q000097:blood*
chemical_list: D009711:Nucleotides; D009536:Niacinamide; D003404:Creatinine; C005211:N'-methyl-2-pyridone-5-carboxamide