1.
Methylguanidine is a suspected uraemic toxin that accumulates in
renal failure. 2. We measured
methylguanidine in the plasma of dogs with acute ischaemic-induced
renal failure and in the plasma and urine of dogs with spontaneous
chronic renal insufficiency, using a highly sensitive method involving solid-phase extraction followed by h.p.l.c. with post-column fluorescence detection. 3. Constriction of the remaining renal artery of four uninephrectomized dogs for 90 min resulted in a significant (P less than 0.01) increase in plasma
creatinine concentration after 24 h (from 113 +/- 3 to 303 +/- 50 mumol/l; mean +/- SEM). Over the next 14 days, plasma
creatinine fell towards baseline concentrations. Plasma
methylguanidine also increased significantly (P less than 0.05) 24 h after renal occlusion (from 0.16 +/- 0.04 to 0.86 +/- 0.32 mumol/l) and showed a similar pattern to the plasma
creatinine concentration. 4. In a further four dogs, administration of
mannitol (2 g/kg) at the time of reperfusion significantly attenuated these responses. 5. Dogs with
chronic renal failure demonstrated increased plasma concentrations and urinary excretion of
methylguanidine, and the levels appeared to be related to the severity of
renal insufficiency. Thus, the dogs with the highest plasma
creatinine concentrations and lowest
creatinine clearances had the highest plasma
methylguanidine concentrations. The clearance of
methylguanidine exceeded that of
creatinine, indicating that the toxin undergoes renal tubular secretion.