Urine osmolality, cyclic AMP and aquaporin-2 in urine of patients under lithium treatment in response to water loading followed by vasopressin administration

Ingeborg Wilting, Ruben Baumgarten, Kris L. L. Movig, Jan van Laarhoven, Alfred J. Apperloo, Willem A. Nolen, Eibert R. Heerdink, Nine V. A. M. Knoers, Antoine C. G. Egberts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

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 aquaporm-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. (c) 2007 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalEuropean Journal of Pharmacology
Volume566
Issue number1-3
DOIs
Publication statusPublished - 2-Jul-2007

Keywords

  • lithium
  • cyclic AMP
  • aquaporin-2
  • nephrogenic diabetes insipidus
  • vasopressin
  • NEPHROGENIC DIABETES-INSIPIDUS
  • HEALTHY-VOLUNTEERS
  • INDUCED POLYURIA
  • INDUCED NDI
  • ALTERED EXPRESSION
  • TREATED PATIENTS
  • RENAL-FUNCTION
  • EXCRETION
  • KIDNEY
  • RATS

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