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

  • Nephrology – Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease.

Methods

We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium’s effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers.

Results

From a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD.

Discussion

Future studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium’s biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events.

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Acknowledgments

Soham Rej was funded by the Canadian Institutes of Health Research (CIHR) Fellowship Award.

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Authors and Affiliations

  1. Campbell Family Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada

    Soham Rej, Victoria Marshe & Daniel J. Müller

  2. Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Soham Rej & Nathan Herrmann

  3. GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada

    Soham Rej, Shamira Pira, André Do, Dominique Elie & Karl J. Looper

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  1. Soham Rej
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  2. Shamira Pira
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Correspondence to Soham Rej.

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Conflict of interest

Dr. Herrmann has received research funding from Lundbeck, Roche, Pfizer, Transition Therapeutics, and honoraria from AbbVie and Eli Lilly. Dr. Muller has received research funding from Assurex Health and Lundbeck. The remaining authors report no financial or other conflicts.

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Rej, S., Pira, S., Marshe, V. et al. Molecular mechanisms in lithium-associated renal disease: a systematic review. Int Urol Nephrol 48, 1843–1853 (2016). https://doi.org/10.1007/s11255-016-1352-6

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  • DOI: https://doi.org/10.1007/s11255-016-1352-6

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