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

作者：Rej Soham; Pira Shamira; Marshe Victoria; Do Andre; Elie Dominique; Looper Karl J; Herrmann Nathan; Muller Daniel J

来源：International Urology and Nephrology, 2016, 48(11): 1843-1853.

DOI：10.1007/s11255-016-1352-6

• Lithium
• Nephrogenic diabetes insipidus
• Chronic kidney disease
• Molecular mechanisms
• Systematic review

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.
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.
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.
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.

• 出版日期2016-11