EXPRESS: Hyperammonemia in cats with acute (on chronic) kidney disease: associations with urea cycle amino acids, azotemia and acid–base status

Objectives Hyperammonemia occurs in cats with kidney disease although the pathophysiology is poorly understood. The objective of this study was to determine if hyperammonemia in cats with kidney disease is associated with decreased concentrations of plasma amino acids involved in the urea cycle and more severe acid-base derangements. Methods Twenty cats presenting with acute kidney injury (AKI) and acute on chronic kidney disease (AoCKD) were prospectively enrolled. Fasting blood samples were analyzed for ammonia, pH, anion gap, electrolytes, lactate, blood urea nitrogen (BUN), creatinine and phosphorus. Plasma was frozen at -80 o C and shipped for amino acid analysis. Results Five of 20 cats had an AKI and 15/20 had AoCKD. Median age and weight were 12 years (range 3-14) and 4.5 kg (range 3-5.6), respectively. Seven cats were hyperammonemic (median 252 µmol/l, range 113-886) and 13 were not (median 23 µmol/l, range 11-49). Creatinine, BUN and phosphorus were significantly higher in hyperammonemic cats. BUN and phosphorus correlated with ammonia. Fifteen of 20 cats (75%) were acidotic but there was no difference in lactate or blood and urine pH between the cats with and without hyperammonemia. The anion gap was higher (29.6, range 27-40 vs 25.1, range 11-34) and serum bicarbonate lower (9 mEq/L, range 4.8-13.5 vs 11.9, range 8-24.2) in hyperammonemic cats. Median plasma citrulline (47 nMol/mL, range 31-128 vs 22, range 12-37) and ornithine (20 nMol/mL, range 12-33 vs 10, range 7-35) but not arginine concentrations were significantly higher in hyperammonemic cats (p<0.05). Plasma citrulline concentrations were positively correlated with serum creatinine (r = 0.621, p = 0.003). Conclusions and relevance Hyperammonemic cats with AKI/AoCKD do not have deficiencies in urea cycle amino acid concentrations but do have more severe azotemia with accompanying high anion gap metabolic acidosis. Increases in citrulline may reflect decreased kidney function.