Kidney protein dynamics and ammoniagenesis in humans with chronic metabolic acidosis.

Giacomo Garibotto, Antonella Sofia, Cristina Robaudo, Stefano Saffioti, Maria Rita Sala, Daniela Verzola, Monica Vettore, Rodolfo Russo, Vanessa Procopio, Giacomo Deferrari, Paolo Tessari

Division of Nephrology, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, 16132 Genoa, Italy. gari@unige.it

Journal of the American Society of Nephrology : JASN 2004 Jun

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To evaluate the effects of chronic metabolic acidosis on protein dynamics and amino acid oxidation in the human kidney, a combination of organ isotopic ((14)C-leucine) and mass-balance techniques in 11 subjects with normal renal function undergoing venous catheterizations was used. Five of 11 studies were performed in the presence of metabolic acidosis. In subjects with normal acid-base balance, kidney protein degradation was 35% to 130% higher than protein synthesis, so net protein leucine balance was markedly negative. In acidemic subjects, kidney protein degradation was no different from protein synthesis and was significantly lower (P < 0.05) than in controls. Kidney leucine oxidation was similar in both groups. Urinary ammonia excretion and total ammonia production were 186% and 110% higher, respectively, and more of the ammonia that was produced was shifted into urine (82% versus 65% in acidemic subjects versus controls). In all studies, protein degradation and net protein balance across the kidney were inversely related to urinary ammonia excretion and to the partition of ammonia into urine, but not to total ammonia production, arterial pH, [HCO(-)(3)], urinary flow, the uptake of glutamine by the kidney, or the ammonia released into the renal veins. The data show that response of the human kidney to metabolic acidosis includes both changes in amino acid uptake and suppression of protein degradation. The latter effect, which is likely induced by the increase in ammonia excretion and partition into the urine, is potentially responsible for kidney hypertrophy.

Citation

Giacomo Garibotto, Antonella Sofia, Cristina Robaudo, Stefano Saffioti, Maria Rita Sala, Daniela Verzola, Monica Vettore, Rodolfo Russo, Vanessa Procopio, Giacomo Deferrari, Paolo Tessari. Kidney protein dynamics and ammoniagenesis in humans with chronic metabolic acidosis. Journal of the American Society of Nephrology : JASN. 2004 Jun;15(6):1606-15