Soham Rej1,2,3, Shamira Pira4, Victoria Marshe5, André Do4, Dominique Elie4, Karl J Looper4, Nathan Herrmann6, Daniel J Müller5. 1. Campbell Family Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada. soham.rej@mail.mcgill.ca. 2. Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. soham.rej@mail.mcgill.ca. 3. GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada. soham.rej@mail.mcgill.ca. 4. GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada. 5. Campbell Family Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada. 6. Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
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.
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.
Authors: Lakshmi N Yatham; Sidney H Kennedy; Sagar V Parikh; Ayal Schaffer; Serge Beaulieu; Martin Alda; Claire O'Donovan; Glenda Macqueen; Roger S McIntyre; Verinder Sharma; Arun Ravindran; L Trevor Young; Roumen Milev; David J Bond; Benicio N Frey; Benjamin I Goldstein; Beny Lafer; Boris Birmaher; Kyooseob Ha; Willem A Nolen; Michael Berk Journal: Bipolar Disord Date: 2012-12-12 Impact factor: 6.744
Authors: Reena Rao; Ming-Zhi Zhang; Min Zhao; Hui Cai; Raymond C Harris; Matthew D Breyer; Chuan-Ming Hao Journal: Am J Physiol Renal Physiol Date: 2004-12-07
Authors: Rikke Nørregaard; Shixin Tao; Line Nilsson; James R Woodgett; Vijayakumar Kakade; Alan S L Yu; Christiana Howard; Reena Rao Journal: Am J Physiol Renal Physiol Date: 2015-01-21
Authors: Jennifer J Bedford; John P Leader; Rena Jing; Logan J Walker; Janet D Klein; Jeff M Sands; Robert J Walker Journal: Am J Physiol Renal Physiol Date: 2008-01-23
Authors: Leonardo Tondo; Maria Abramowicz; Martin Alda; Michael Bauer; Alberto Bocchetta; Lorenza Bolzani; Cynthia V Calkin; Caterina Chillotti; Diego Hidalgo-Mazzei; Mirko Manchia; Bruno Müller-Oerlinghausen; Andrea Murru; Giulio Perugi; Marco Pinna; Giuseppe Quaranta; Daniela Reginaldi; Andreas Reif; Philipp Ritter; Janusz K Rybakowski; David Saiger; Gabriele Sani; Valerio Selle; Thomas Stamm; Gustavo H Vázquez; Julia Veeh; Eduard Vieta; Ross J Baldessarini Journal: Int J Bipolar Disord Date: 2017-08-01
Authors: Marlien Torfs; Titia Hompes; Michael Ceulemans; Kristel Van Calsteren; Christine Vanhole; Anne Smits Journal: Int J Environ Res Public Health Date: 2022-08-16 Impact factor: 4.614