METABOLIC ADAPTATION OF THE KIDNEY TO HYPERAMMONEMIA DURING CHRONIC LIVER INSUFFICIENCY IN THE RAT

The aim of this study was to evaluate the role of renal ammonia and gl utamine metabolism in the metabolic adaptation to chronic liver insuff iciency-induced hyperammonemia in the rat. To this purpose, urinary ex cretion, renal net exchange and tissue concentrations of ammonia and a mino acids were measured in anesthetized, normal control rats that did not undergo surgery, in control rats that underwent sham surgery, in rats that underwent portacaval shunting and in rats that underwent bot h portacaval shunting and bile duct ligation. Rats that underwent sham surgery and portacaval shunting were pair-fed with rats that underwen t portacaval shunting and biliary obstruction, to correct for anorexia in that group, and all rats that were operated on were studied 7 and 14 days after surgery. Arterial ammonia and glutamine levels were elev ated in groups that underwent portacaval shunting and portacaval shunt ing plus biliary obstruction at all time points. At days 7 and 14, tot al renal ammonia production decreased in rats that underwent portacava l shunting and in rats that underwent portacaval shunting plus biliary obstruction, associated with a 50% decrease in net renal glutamine up take and strongly diminished net ammonia release into the renal vein, which was most prominent in the group that underwent portacaval shunti ng plus biliary obstruction. Urinary ammonia excretion was similar in rats that underwent portacaval shunting and in those that underwent sh am surgery but was increased more than 200% at days 7 and 14 in rats t hat underwent portacaval shunting plus biliary obstruction. In this gr oup, in contrast to portacaval-shunted rats, the kidney appeared to be an organ of net ammonia disposal from the body. In separate experimen ts in unanesthetized, unrestrained rats, similar changes in urinary am monia excretion were observed without changes in arterial pH, excludin g an effect of anesthesia or pH on the obtained results. These results indicate that the kidney plays an important role in the metabolic ada ptation to hyperammonemia during chronic liver insufficiency in the ra t.