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Overnight glucose infusion suppresses renal ammoniagenesis and reduces hyperammonaemia induced by a simulated bleed in cirrhotic patients
Author(s) -
Mpabanzi L.,
Deutz N.,
Hayes P. C,
Dejong C. H. C.,
Olde Damink S. W. M.,
Jalan R.
Publication year - 2012
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2012.05044.x
Subject(s) - gluconeogenesis , medicine , endocrinology , bleed , cirrhosis , kidney , alanine , metabolism , amino acid , chemistry , biochemistry , surgery
Summary Background A simulated upper gastrointestinal ( UGI ) bleed in cirrhotic patients has been shown to induce hyperammonaemia. The kidney was the site of this exaggerated ammoniagenesis with alanine as substrate. Administration of alanine to decompensated cirrhotic patients did not change hepatic gluconeogenesis, but resulted in increased ammoniagenesis. We hypothesise that reduced hepatic glycogen stores result in hyperglucagonaemia which may drive increased renal gluconeogenesis and therefore alanine uptake and renal ammoniagenesis. Aim To determine whether an overnight glucose infusion lowers renal ammoniagenesis by reducing hyperglucagonaemia and renal ammoniagenesis. Methods Patients with decompensated cirrhosis were studied in a cross‐over design. An UGI bleed was simulated via intragastric administration of an amino acids mixture mimicking the haemoglobin molecule after a 12‐h overnight fast (F‐group) or after a 12‐h treatment with 20% glucose solution (G‐group). Results Before the simulated bleed the glucagon levels were 21 (15–31) pmol/L in the F‐group and 15 (9–21) pmol/L in the G‐group ( P < 0.01). After the simulated bleed, arterial ammonia levels increased in both groups [F‐group: 73–118 μmol/L ( P = 0.01); G‐group 64–87 μmol/L ( P = 0.01)]. The enhancement of hyperammonaemia was significantly higher in the F‐group (45 [19–71] μmol/L) compared with the G‐group (23 [13–39] μmol/L) ( P = 0.01). The difference in renal ammoniagenesis during the simulated bleed in the F‐group was 399 (260–655) nmol/kg/bwt/min and was significantly higher than in the G‐group 313 (1–498) nmol/kg/bwt/min ( P = 0.05). Conclusions Overnight glucose infusion results in reduced renal ammoniagenesis and attenuates ammonia levels. These observations have implications for the development of nutritional strategies in hyperammonaemic patients.