Effect of Arginine or Creatinine Administration on the Urinary Excretion of Methylguanidine

The metabolic pathway of methylguanidine (MG) is mainly speculated from the change in urinary excretion of MG in the arginine (Arg)-injected normal rat, the creatinine (Cr)-injected normal rat, and the Arg-injected uremic rat. 15N-Arg was ingested to 2 uremic patients. Arg administration resulted in marked increase in urinary MG excretion both in the uremic rat and patient, but not in the normal rat. In the first phase of the 15N-Arg ingestion experiment, a rapid rise of 15N atom percent excess of urinary MG was observed in the uremic patient. In the second phase of this study, after 24 h of 15N-Arg ingestion, the 15N atom percent excess of urinary Cr and that of MG closely paralleled. These findings imply that there might be two metabolic origins of MG: one is a formation of MG from Arg itself or an Arg metabolite other than Cr, the other a pathway producing MG via Cr. The former is compatible with the hypothesis by Cohen.