[Dialysis of methylguanidine and hypothesis on the middle molecules]

The formulation of "Methilguanidine (MG) hypothesis" started from previous researches that showed that uramic symptoms in dogs intoxicated by MG were present. Being a low molecular weight molecule, MG as Urea (U) and Creatine (CR), should not be considered an "uraemic toxin" according with the "middle molecules hipothesis". We have studied, during peritoneal and various hemodialysis schedules, MG "in vivo" and "in vitro" clearance, post-dialytic rebound, plasmaaproteins binding, intra and extracellular distribution. "In vitro" MG clearance is intermediate between U and CR, but "in vivo" MG clearance is lower than U and CR: what is explained by MG prevalent intracellular distribution and by the increasing plasm proteins binding during hemodialysis alkalinisation. 12 hours after high efficiency dialysis MG has an higher rebound than U and CR because of the slow and constant MG flow from intracellular fluid to plasma. On the other hand a continuous equilibrium between intra extracellular MG happens during the longer and less efficient peritoneal dialysis: MG plasma level 12 hours after peritoneal dialysis is the same that after high efficiency hemodialysis; on the contrary U and CR plasma levels are higher after peritoneal than after hemodialysis. In spite of the low molecular weight MG dialysis is different than U and CR. Good clinical condition of patients on peritoneal and low-flow-dialysis which represented the basis of the ""MG hypothesis": infact MG removal is the same during peritoneal and hemodialysis.