Molecular characterization of water balance disturbances

Contains fulltext : 191600.pdf (publisher's version ) (Open Access)The kidneys filtrate about 170–180 L of blood every day. If these large volumes were excreted unchanged as urine, it would be necessary to ingest huge amounts of water to stay in balance. This is avoided by the selective reabsorption of water in the collecting duct principal cells that express AQP2 water channel. Decrease in the abundance of AQP2 on the cell surface directly affects the urine concentrating ability resulting in diseases such nephrogenic diabetes insipidus (NDI). The most common form of NDI is a side effect of lithium treatment that is given to bipolar patients. This thesis aimed to gain insight into pathophysiological mechanisms involved in the development of renal side effects of lithium and explored the possibility to introduce novel treatments for Li-NDI. We showed that lithium induced proliferation of principal cells but caused a G2 cell cycle arrest that explains collecting duct remodeling seen after long-term lithium treatment. Moreover, lithium caused a metabolic shift towards aerobic glycolysis and glutaminolysis and we found that the cell cycle status of the principal cells determines the abundance of AQP2.Radboud University, 21 juni 2018Promotor : Deen, P.M.T. Co-promotor : Groot, T. d