Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus.
Nephrogenic diabetes insipidus is a clinical sub-type of a diversely expounded disorder, named diabetes insipidus. It is characterized by inability of the renal cells to sense and respond to the stimulus of vasopressin. Amongst its various etiologies, one of the most inevitable causes includes lithium-induced instigation. Numerous studies reported marked histological damage to the kidneys upon long-term treatment with lithium. The recent researches have hypothesized many lithium-mediated mechanisms to explain the damage and dysfunction caused in the kidneys following lithium exposure. These mechanisms, widely, intend to justify the lithium-induced electrolyte imbalance, its interference with some vital proteins and a specific steroidal hormone, obstruction caused to a certain imperative transducer pathway and the renal tubular acidification defect produced on its prolonged therapy. Thorough study of such mechanisms aids in better understanding of the role of lithium in the pathophysiology of this disorder. Hence, the ameliorated knowledge regarding disease-pathology might prove beneficial in developing therapies that aim on disrupting the various lithium-mediated pathways. Hence, this may effectively lead to the demonstration of a novel treatment for nephrogenic diabetes insipidus, which is, at present, limited to the use of diuretics which block lithium reuptake into the body.
Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. Electronic address: tapanbehl31@gmail.com.
Tapan
T
Behl
Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
Anita
A
Kotwani
Department of Pharmacy, Chandigarh College of Pharmacy, Mohali, Punjab, India.
Ishneet
I
Kaur
Department of Animal Husbandry, Junga, Shimla, Himachal Pradesh, India.
Heena
H
Goel
D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy; D018500:Diabetes Insipidus, Nephrogenic / Q000139:chemically induced*; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects* / Q000627:therapeutic use
D018020:Lithium Compounds
Aldosterone; Aquaporin-2 (AQP-2); Epithelial sodium channel (ENaC); GSK3-beta (Glycogen synthase kinase 3-beta); Vasopressin