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Molecular mechanisms in lithium-associated renal disease: a systematic review

Soham Rej1,2,3, Shamira Pira4, Victoria Marshe5

  • 1Campbell Family Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada. soham.rej@mail.mcgill.ca.

International Urology and Nephrology
|July 1, 2016
PubMed
Abstract

Insights

This review explores molecular mechanisms behind lithium-induced kidney damage, focusing on pathways involved in nephrogenic diabetes insipidus. Further research is needed to validate findings in humans and investigate chronic kidney disease for safer lithium use.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Lithium is a crucial treatment for bipolar disorder and treatment-resistant depression.
  • Renal adverse effects limit lithium's clinical utility.
  • Understanding molecular mechanisms is key to preventing and treating lithium-associated renal disease.

Purpose of the Study:

  • To systematically review molecular mechanisms underlying lithium's effects on the kidney.
  • To identify pathways implicated in lithium-associated nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD).

Main Methods:

  • Systematic literature search of MEDLINE, Embase, and PsychINFO databases.
  • Inclusion of original research articles published before November 2015.
  • Focus on studies investigating molecular markers of lithium's impact on NDI and CKD.

Main Results:

  • 71 pre-clinical and 2 clinical studies were identified.
  • Molecular alterations were observed in calcium signaling, inositol monophosphate, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation pathways.
  • Most identified mechanisms were linked to NDI, with limited research on CKD.

Conclusions:

  • Future research should validate findings in human subjects.
  • Investigating chronic kidney disease (CKD) is crucial due to its clinical relevance.
  • Improved understanding will inform personalized medicine for safer lithium prescribing and reduced renal adverse events.
Keywords:
Chronic kidney diseaseLithiumMolecular mechanismsNephrogenic diabetes insipidusSystematic review

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