Nicotinamide metabolites accumulate in the tissues of uremic rats

Objective: N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY) are nicotinamide (NA) metabolites described by our group and considered to be uremic toxins. Plasma concentration of Met2PY and Met4PY in end-stage renal disease (ESRD) is several-fold higher in comparison with healthy controls. However, there are no data about the concentrations of these compounds in different tissues. The aim of this study was to establish whether the observed high concentrations of these compounds were also present in different tissues of uremic animals. Methods: This study was conducted in 10 5/6 nephrectomized male Wistar rats and 10 sham-operated animals. Concentrations of nicotinamide and its end products were measured using high-performance liquid chromatography and mass spectrometry. Results: We observed significant elevations of Met2PY and Met4PY in tissues of uremic rats. The greatest differences between healthy and uremic rats were observed in the liver, lungs, and skeletal muscles. Accumulation in the kidney and heart was not so pronounced, but in the case of Met4PY was statistically significant. Conclusions: We found that Met2PY and Met4PY accumulate, not only in the blood but also in tissues of uremic rats. (c) 2008 by the National Kidney Foundation, Inc.