Accumulation of the endogenous L‐arginine analogue NG‐monomethyl‐L‐arginine in human end‐stage renal failure patients on regular haemodialysis

We measured plasma levels of L-arginine, its analogue NG-monomethyl-L-arginine (L-NMMA), and related amino acids in normal subjects and uraemic patients (n = 31), before and after haemodialysis. Plasma levels of L-arginine were reduced to less than half of normal values in uraemic subjects compared with controls, and were not affected by haemodialysis. L-NMMA was not detectable in non-uraemic subjects, but markedly elevated in uraemic patients. In parallel, we used human red blood cells as a model to study the effect of L-NMMA upon the transport of L-arginine. L-NMMA trans-stimulated L-arginine transport significantly, confirming that L-arginine and L-NMMA share common transport pathways. Our results suggest altered L-arginine metabolism and the presence of an increased concentration of a NO synthase inhibitor in uraemia. We propose that alterations in plasma L-arginine levels and increased production of L-arginine analogues will alter NO synthesis and may help to explain some pathological changes seen in uraemia.