Lithium increases ammonium excretion leading to altered urinary acid-base buffer composition.
Francesco Trepiccione1,2, Claudia Altobelli3, Giovambattista Capasso3,4
1Department of Biomedicine, Aarhus University, Aarhus, Denmark. francesco.trepiccione@unicampania.it.
Journal of Nephrology
|November 28, 2017
Summary
Lithium (Li+) treatment can cause kidney issues, but new research suggests it may not be distal renal tubular acidosis (dRTA). Instead, altered ammonium excretion and urine buffering mechanisms in rats may explain previous findings.
Area of Science:
- Nephrology
- Renal Physiology
- Acid-Base Balance
Background:
- Previous studies linked lithium (Li+) salt administration to voltage-dependent distal renal tubular acidosis (dRTA).
- This was based on impaired urine-blood pCO2 response to NaHCO3 and normalization with neutral phosphate or Na2SO4 in animal models.
- The precise mechanisms behind Li+-induced dRTA remain unclear.
Purpose of the Study:
- To investigate the time course of urinary acid-base parameters in rats treated with lithium chloride (LiCl) or other salts.
- To elucidate the underlying mechanisms of Li+-induced renal tubular dysfunction.
- To re-evaluate the classification of Li+-induced kidney issues as dRTA.
Main Methods:
- A 7-day time-course study of urinary acid-base parameters in rats receiving LiCl, LiCitrate, NaCl, or NaCitrate.
- Measurement of urine volume, pH, pCO2, and ammonium (NH4+) excretion.
- Assessment of NBCn1 expression in rat kidneys and NH4+ excretion in ENaC-cKO mice.
Main Results:
- LiCl induced significant polyuria and mild metabolic acidosis, with a biphasic response.
- Later phases (day 3 onwards) showed increased NH4+ excretion and decreased urine pCO2, indicating NH3/NH4+ as the primary buffer.
- Upregulation of NBCn1 and altered NH4+ excretion in ENaC-cKO mice supported a role for the collecting duct (CD) and ammonium handling.
Conclusions:
- The study questions the existence of a voltage-dependent Li+-induced dRTA in rats treated with LiCl for 7 days.
- Alkaline urine pH, driven by NH3/NH4+ buffering, may have been misinterpreted as dRTA in prior research.
- Findings suggest a primary role for altered ammonium excretion and buffering in Li+-induced renal effects.
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