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Birgitte Mønster Christensen

Lithium increases ammonium excretion leading to altered urinary acid-base buffer composition

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  • Francesco Trepiccione
  • ,
  • Claudia Altobelli, Department of Cardio-Thoracic and Respiratory Science, University of Campania "Luigi Vanvitelli", Via Pansini 5, 80131, Naples, Italy.
  • ,
  • Giovambattista Capasso, Istituto di Ricerche Gaetano Salvatore, Biogem S.c.a.r.l., Naples, Italy., Department of Cardio-Thoracic and Respiratory Science, University of Campania "Luigi Vanvitelli", Via Pansini 5, 80131, Naples, Italy. francesco.trepiccione@unicampania.it.
  • ,
  • Birgitte Mønster Christensen
  • Sebastian Frische

Previous reports identify a voltage dependent distal renal tubular acidosis (dRTA) secondary to lithium (Li+) salt administration. This was based on the inability of Li+-treated patients to increase the urine-blood (U-B) pCO2 when challenged with NaHCO3 and, the ability of sodium neutral phosphate or Na2SO4 administration to restore U-B pCO2 in experimental animal models. The underlying mechanisms for the Li+-induced dRTA are still unknown. To address this point, a 7 days time course of the urinary acid-base parameters was investigated in rats challenged with LiCl, LiCitrate, NaCl, or NaCitrate. LiCl induced the largest polyuria and a mild metabolic acidosis. Li+-treatment induced a biphasic response. In the first 2 days, proper urine volume and acidification occurred, while from the 3rd day of treatment, polyuria developed progressively. In this latter phase, the LiCl-treated group progressively excreted more NH4+ and less pCO2, suggesting that NH3/NH4+ became the main urinary buffer. This physiological parameter was corroborated by the upregulation of NBCn1 (a marker of increased ammonium recycling) in the inner stripe of outer medulla of LiCl treated rats. Finally, by investigating NH4+ excretion in ENaC-cKO mice, a model resistant to Li+-induced polyuria, a primary role of the CD was confirmed. By definition, dRTA is characterized by deficient urinary ammonium excretion. Our data question the presence of a voltage-dependent Li+-induced dRTA in rats treated with LiCl for 7 days and the data suggest that the alkaline urine pH induced by NH3/NH4+ as the main buffer has lead to the interpretation dRTA in previous studies.

TidsskriftJournal of Nephrology
Sider (fra-til)385-393
Antal sider9
StatusUdgivet - jun. 2018

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