title: Molecular mechanisms in lithium-associated renal disease: a systematic review.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Campbell Family Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada. soham.rej@mail.mcgill.ca.|Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. soham.rej@mail.mcgill.ca.|GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada. soham.rej@mail.mcgill.ca.
authors.forename: Soham
authors.initials: S
authors.lastname: Rej
authors.affiliation: GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada.
authors.forename: Shamira
authors.initials: S
authors.lastname: Pira
authors.affiliation: Campbell Family Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
authors.forename: Victoria
authors.initials: V
authors.lastname: Marshe
authors.affiliation: GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Do
authors.affiliation: GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Elie
authors.affiliation: GERI-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montréal, QC, Canada.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Looper
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.affiliation: Campbell Family Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D018500:Diabetes Insipidus, Nephrogenic / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D008094:Lithium / Q000009:adverse effects*; D011453:Prostaglandins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
chemical_list: D020346:Aquaporins; D011453:Prostaglandins; D043562:Receptors, G-Protein-Coupled; D027981:Symporters; D014667:Vasopressins; D008094:Lithium; D012964:Sodium; D002118:Calcium
keywords: Chronic kidney disease; Lithium; Molecular mechanisms; Nephrogenic diabetes insipidus; Systematic review