Clinico-biochemical aspects of guanidine compounds in uraemic toxicity.

"Uraemia" literally means "urine in blood". With the advancement of basic medical sciences, it is being better understood. The clinical syndrome of uraemia is due to the failure of not only the excretory but also the metabolic, regulatory and endocrine functions of the kidney. Apart from the "retained toxic metabolites", a number of guanidine derivatives had been found which are now considered to be more important in the causation of the uraemic syndrome. Cohen had hypothesised that nitrogen retention in uraemia causes an aberration in the urea cycle that in turn leads to the production of guanidinosuccinic acid (GSA) in large amounts. However, it appears that methylguanidine (MG) is produced from the degradation of creatinine by the gut flora in uraemics. Both GSA and MG are proved to be toxic. The role of GSA in uraemic neurotoxicity and coma is still controversial and needs further investigation. It is possible that the combined effects of a number of compounds are responsible for the development of the uraemic syndrome.