Reply to the Letter to the Editor entitled "Response to Statins in the Prevention of Lithium-Associated Diabetes Insipidus: Preliminary Findings"

Nephrogenic Diabetes Insipidus (NDI) is a common complication of lithium (Li+) treatment. Li+ inhibits vasopressin-stimulated translocation of the water channel aquaporin 2 (AQP2) to the apical membrane of kidney collecting duct (CD) principal cells, thereby limiting water reabsorption in the CD (1). Long-term exposure to Li+ may also down-regulate AQP2 gene expression (2). This results in the excretion of a large volume of hypoosmotic urine. We previously showed that statins increase AQP2 abundance at the apical plasma membrane of CD principal cells in vivo in a mouse model of genetically-induced NDI (3). The preliminary data presented in the Letter by Elie et al., unambiguously showed that statins attenuate the drop in urine osmolality, observed also in Li+-induced NDI. They showed that none of the statins users observed in their study, had urine osmolality lower than 300mOsm/Kg during Li+ treatment. In line of principle, this is predictable on the base of the mechanism of action of statins on AQP2 trafficking. This interesting, preliminary evidence is of great therapeutic importance, for statins might help attenuating the side effects of lithium therapy in the kidney. Further studies in Li+-treated animals and measurements of AQP2 urine excretion in patients, are necessary to understand the mechanism by which statins counteract the drop of urine osmolality in Li-induced NDI