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 μmol/l), increasing with degree of renal failure through ESRF (55.1 μmol/l) and HD patients (70.9 μmol/l) and being highest in CAPD patients (216.7 μmol/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. Conclusion: 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.