title: Urine osmolality, cyclic AMP and aquaporin-2 in urine of patients under lithium treatment in response to water loading followed by vasopressin administration.
abstract: Lithium is the drug that is most frequently associated with acquired nephrogenic diabetes insipidus (NDI). The exact mechanism of lithium-induced NDI in man is unknown. The aim of the present study was to investigate the kidney response to minimal and maximal stimulation of the kidney urine concentrating mechanism by measuring urine osmolality, and urine levels of cAMP and AQP-2 in urine of patients under long-term lithium treatment. Twenty patients under long-term lithium treatment were included. The kidney urinary 3',5'-cyclic adenosine monophosphate (cyclic AMP), aquaporin-2 levels and urine osmolality were determined during a situation of minimal kidney urine concentrating activity (induced by water loading) and during a situation following maximal stimulation of kidney urine concentrating activity (induced by 1-desamino-8-D-arginine-vasopressin). Patients were classified as NDI, partial NDI and non-NDI based on maximal reached urine osmolality. The partial correlation (r) between urinary cyclic AMP levels (mol/l) and urine osmolality was 0.94 (P<0.001). No significant correlation was observed between urinary aquaporin-2 levels (mol/mol creatinine) and osmolality nor between urinary cyclic AMP and aquaporin-2 levels. The rise in urinary cyclic AMP but not aquaporin-2 levels upon 1-desamino-8-D-arginine-vasopressin administration after water loading significantly differed between the three categories, decreasing with increasing NDI category. In conclusion we found that in lithium-induced kidney urine concentrating deficit in man, the cyclic AMP generation in response to 1-desamino-8-D-arginine-vasopressin administration after water loading, is impaired. It remains to be elucidated whether principal cells, G-proteins or adenylate cyclase e.g. are the major targets for the mechanism underlying lithium-induced NDI in man.
authors.affiliation: Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht, and Department of Clinical Pharmacy, TweeSteden hospital, Tilburg, The Netherlands.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Wilting
authors.forename: Ruben
authors.initials: R
authors.lastname: Baumgarten
authors.forename: Kris L L
authors.initials: KL
authors.lastname: Movig
authors.forename: Jan
authors.initials: J
authors.lastname: van Laarhoven
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Apperloo
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.forename: Eibert R
authors.initials: ER
authors.lastname: Heerdink
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
authors.forename: Antoine C G
authors.initials: AC
authors.lastname: Egberts
mesh_terms: D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000009:adverse effects*; D051399:Aquaporin 2 / Q000652:urine*; D000242:Cyclic AMP / Q000652:urine*; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage*; D018500:Diabetes Insipidus, Nephrogenic / Q000139:chemically induced / Q000652:urine*; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D014556:Urine / Q000737:chemistry; D014867:Water / Q000008:administration & dosage
chemical_list: D018692:Antimanic Agents; D051399:Aquaporin 2; D018020:Lithium Compounds; D014867:Water; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin