Medline ® Abstract for Reference 22
of 'Treatment of nephrogenic diabetes insipidus'
alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus.
Christensen BM, Zuber AM, Loffing J, Stehle JC, Deen PM, Rossier BC, Hummler E
J Am Soc Nephrol. 2011;22(2):253. Epub 2010 Nov 4.
Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic mice lackingαENaC specifically in the CD (knockout [KO]mice) and littermate controls to chronic lithium treatment. In contrast to control mice, KO mice did not markedly increase their water intake. Furthermore, KO mice did not demonstrate the polyuria and reduction in urine osmolality induced by lithium treatment in the control mice. Lithium treatment reduced AQP2 protein levels in the cortex/outer medulla and inner medulla (IM) of control mice but only partially reduced AQP2 levels in the IM of KO mice. Furthermore, lithium induced expression of H(+)-ATPase in the IM of control mice but not KO mice. In conclusion, the absence of functional ENaC in the CD protects mice from lithium-induced NDI. These data support the hypothesis that ENaC-mediated lithium entry into the CD principal cells contributes to the pathogenesis of lithium-induced NDI.
Water and Salt Research Center, Department of Anatomy, Aarhus University, Wilhelm Meyers Allé3, 8000 Aarhus C, Denmark. email@example.com