RENAL AMMONIA AND GLUTAMINE-METABOLISM DURING LIVER INSUFFICIENCY-INDUCED HYPERAMMONEMIA IN THE RAT

Renal glutamine uptake and subsequent urinary ammonia excretion could be an important alternative pathway of ammonia disposal from the body during liver failure (diminished urea synthesis), but this pathway has received little attention. Therefore, we investigated renal glutamine and ammonia metabolism in mildly hyperammonemic, portacaval shunted r ats and severely hyperammonemic rats with acute liver ischemia compare d to their respective controls, to investigate whether renal ammonia d isposal from the body is enhanced during hyperammonemia and to explore the limits of the pathway. Renal fluxes, urinary excretion, and renal tissue concentrations of amino acids and ammonia were measured 24 h a fter portacaval shunting, and 2, 4, and 6 h after liver ischemia induc tion and in the appropriate controls. Arterial ammonia increased to 24 7+-22 muM after portacaval shunting compared to controls (51+/-8 muM) (P < 0.001) and increased to 934+/-54 muM during liver ischemia (P < 0 .001). Arterial glutamine increased to 697+/-93 muM after portacaval s hunting compared to controls (513+/-40 muM) (P < 0.01) and further inc reased to 3781+/-248 muM during liver ischemia (P < 0.001 ). In contra st to controls, in portacaval shunted rats the kidney net disposed amm onia from the body by diminishing renal venous ammonia release (from 2 67+/-33 to -49+/-59 nmol/100 g body wt per min) and enhancing urinary ammonia excretion from 113+/-24 to 305+/-52 nmol/100 g body wt per min (both P < 0.01 ). Renal glutamine uptake diminished in portacaval shu nted rats compared to controls (-107+/-33 vs. -322+/-41 nmol/100 g bod y wt per min) (P < 0.01). However, during liver ischemia, net renal am monia disposal from the body did not further increase (294+/-88 vs. 14 4+/-101 nmol/100 g body wt per min during portacaval shunting versus l iver ischemia). Renal glutamine uptake was comparable in both hyperamm onemic models. These results indicate that the rat kidney plays an imp ortant role in ammonia disposal during mild hyperammonemia. However, d uring severe liver insufficiency induced-hyperammonemia, ammonia dispo sal capacity appears to be exceeded.