Origin and characteristics of an unusual pyridine nucleotide accumulating in erythrocytes: positive correlation with degree of renal failure.
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.
Carrey
Elizabeth A
EA
Purine Research Unit, Guy's Hospital, 5th Floor, Thomas Guy House, London SE1 9RT, UK. elizabeth.carrey@kcl.ac.uk
Smolenski
Ryszard T
RT
Edbury
Stephen M
SM
Laurence
Arian
A
Marinaki
Anthony M
AM
Duley
John A
JA
Zhu
Limin
L
Goldsmith
David J A
DJ
Simmonds
H Anne
HA
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*
D009711:Nucleotides; D009536:Niacinamide; D003404:Creatinine; C005211:N'-methyl-2-pyridone-5-carboxamide