Relationship between uremic toxins and oxidative stress in patients with chronic renal failure

Uremic toxins play a critical role in the manifestation of the uremic syndrome. This is a consequence of retention of such substances in chronic renal failure patients and interactions between them. To date >100 uremic compounds have been discovered. The aim of this study was to elucidate potential relationships between N-methyl-2-pyridone-5-carboxamide (Me2PY) and N-methyl-4-pyridone-5-carboxamide (Me4PY), two uremic compounds, and different parameters of oxidative stress.

Forty-three non-dialyzed patients at the Nephrological Outpatients Clinic of Gdansk were enrolled and divided into two groups: (i) 20 patients with a mean estimated glomerular filtration rate (eGFR) of 22.7 ml/min/1.73 m(2); and (ii) 23 patients with a mean eGFR of 12.4 ml/min/1.73 m(2). In both groups, the plasma concentrations of uremic toxins (Me2PY, Me4PY, creatinine), malonyldialdehyde (MDA) and carbonyl groups and the erythrocyte concentration of glutathione (GSH) were analyzed. Correlations between uremic toxins and oxidative stress markers were calculated using Pearson's correlation.

We observed significant correlations between serum creatinine and Me2PY (r=0.68; p=0.00001), eGFR and Me2PY (r=-0.55; p=0.00001), Me4PY and serum creatinine (r=0.64, p=0.00001), Me4PY and eGFR (r=-0.59; p=0.00008), MDA and Me2PY (r=0.42; p=0.006), MDA and Me4PY (r=0.38; p=0.02), GSH and Me2PY (r=-0.37; p=0.02) and GSH and Me4PY (r=-0.46; p=0.005), and in particular in patients with severe renal impairment.

We conclude that there is a relationship between the novel uremic toxins described and oxidative stress markers. However, elucidation of the exact pathogenetic links requires further detailed studies.