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Amiloride restores renal medullary osmolytes in lithium-induced nephrogenic diabetes insipidus

Departments of ¹Physiology and ²Medicine, University of Otago, Dunedin, New Zealand; and ³Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

Submitted 22 November 2007 ; accepted in final form 11 January 2008

In lithium-induced nephrogenic diabetes insipidus (NDI), alterations in renal medullary osmolyte concentrations have been assumed but never investigated. Amiloride can modify lithium-induced NDI, but the impact of amiloride in lithium-induced NDI on renal medullary osmolytes, aquaporins, and urea transporters is unknown and is the basis of this study. Rats fed lithium (60 mmol/kg dry food) over 4 wk developed NDI. Urine osmolality fell to 287 ± 19 mosmol/kgH₂O (controls 1,211 ± 90 mosmol/kgH₂O). Organic osmolytes in the renal medulla showed significant decreases compared with controls [inositol 221 ± 35 to 85 ± 10 mmol/kg protein; sorbitol 35 ± 9 to 3 ± 1 mmol/kg protein; glycerophosphorylcholine (GPC) 352 ± 80 to 91 ± 20 mmol/kg protein; and glycine betaine 69 ± 11 to 38 ± 38 mmol/kg protein]. Medullary urea content fell from 2,868 ± 624 to 480 ± 117 mmol/kg protein. Concurrent administration of amiloride (0.2 mmol/l) in the drinking water restored urine osmolality (1,132 ± 154 mosmol/kgH₂O), and reduced urine volume. Medullary osmolyte content were restored to control values (inositol, 232 ± 12; sorbitol 32 ± 6; GPC, 244 ± 26; glycine betaine, 84 ± 5 mmol/kg protein). Medullary urea rose to 2,122 ± 305 mmol/kg protein. Reduced AQP2, AQP3, and urea transporter (UT-A1) expression was significantly reversed following amiloride therapy. Data presented here provide further understanding of how amiloride may substantially restore the lithium-induced impaired renal concentrating mechanism.

aquaporin; osmolytes; urea transporter

This article has been cited by other articles:

				J. J. Bedford, S. Weggery, G. Ellis, F. J. McDonald, P. R. Joyce, J. P. Leader, and R. J. Walker Lithium-induced Nephrogenic Diabetes Insipidus: Renal Effects of Amiloride Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1324 - 1331. [Abstract] [Full Text] [PDF]