Bicarbonaturic effect of lysine in the dog

The infusion of 55 mumoles/kg/min of L-lysine monohydrochloride increased mean fractional bicarbonate excretion (CHCO3/GFR) from 0.01 to 0.29. This massive bicarbonaturia was observed in the absence of any significant fall in GFR or kidney cortex ATP content. Kaliuresis and urinary PCO2 also increased markedly while phosphaturia remained minimal. CHCO3/GFR reached 0.52 during the infusion of 110 mumoles/kg/min of L-lysine monohydrochloride and 0.65 when carbonic anhydrase inhibition was superimposed. Bicarbonaturia remained minimal during the infusion of 55 mumoles/kg/min of L-lysine dihydrochloride. However the same amount of isoelectric L-lysine and sodium L-lysinate increased CHCO3/GFR to 0.68 and 0.76, respectively. In dogs with ligated renal pedicles, a 1:1 relationship was observed between cellular entry of lysine and the combined shift of sodium and potassium from cell to extracellular fluid. Marked accumulation of lysine was observed in the kidney following the infusion of either L-lysine monohydrochloride or L-lysine dihydrochloride. This study demonstrates that lysine inhibits in the proximal tubule the fraction of bicarbonate reabsorption which is not mediated by carbonic anhydrase activity. This effect is best explained by trapping of hydrogen ions in the tubular cell following luminal and antiluminal entry of lysine in unionized form. The possible role of lysine as a poorly reabsorbable cation is also recognized.