Opposite effects on regulation of urea synthesis by early and late uraemia in rats.
OBJECTIVE
Acute and chronic kidney failure lead to catabolism with loss of lean body mass. Up-regulation of hepatic urea synthesis may play a role for the loss of body nitrogen and for the level of uraemia. The aims were to investigate the effects of early and late experimental renal failure on the regulation of hepatic urea synthesis and the expression of urea cycle enzyme genes in the liver.


METHODS
We examined the in vivo capacity of urea nitrogen synthesis, mRNA levels of urea cycle enzyme genes, and N-balances 6 days and 21 days after 5/6th partial nephrectomy in rats, and compared these data with pair- and free-fed control animals.


RESULTS
Compared with pair-fed animals, early uraemia halved the in vivo urea synthesis capacity and decreased urea gene expressions (P<0.05). In contrast, late uraemia up-regulated in vivo urea synthesis and expression of all urea genes (P<0.05), save that of the flux-generating enzyme carbamoyl phosphate synthetase. The N-balance in rats with early uraemia was markedly negative (P<0.05) and near zero in late uraemia.


CONCLUSIONS
Early uraemia down-regulated urea synthesis, so hepatic ureagenesis was not in itself involved in the negative N-balance. In contrast, late uraemia up-regulated urea synthesis, which probably contributed towards the reduced N-balance of this condition. These time-dependent, opposite effects on the uraemia-induced regulation of urea synthesis in vivo were not related to food restriction and probably mostly reflected regulation on gene level.
Nielsen
Susanne Schouw
SS
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, 44 Noerrebrogade, DK-8000 Aarhus C, Denmark. schouw@akhphd.au.dk
Grøfte
Thorbjørn
T
Grønbaek
Henning
H
Tygstrup
Niels
N
Vilstrup
Hendrik
H
D058186:Acute Kidney Injury / Q000378:metabolism / Q000601:surgery; D000818:Animals; D001806:Blood Urea Nitrogen; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics / Q000378:metabolism*; D004798:Enzymes; D015971:Gene Expression Regulation, Enzymologic; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000601:surgery; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000097:blood / Q000378:metabolism* / Q000652:urine
D004798:Enzymes; D012333:RNA, Messenger; D014508:Urea; D002222:Carbamoyl-Phosphate Synthase (Ammonia)