Lithium-induced reduction in urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion in healthy volunteers

doi:doi:10.1111/j.1523-1755.2005.00081.x

Abstract

Lithium-induced reduction in urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion in healthy volunteers.

Background

Lithium therapy is associated with the development of nephrogenic diabetes inspidus. Experimentally, lithium inhibits arginine vasopressin (AVP)-stimulated translocation of cytoplasmic aquaporin 2 (AQP2) to the apical membrane. Clinically, the actions of lithium on renal tubular function are less clearly established. This study examined the effects of four weeks of lithium therapy on desmopressin (dDAVP)-stimulated urinary concentrating ability in healthy volunteers.

Methods

Eleven healthy volunteers underwent baseline urinary concentrating ability studies which were repeated following 4 weeks therapy with lithium carbonate (250 mg twice a day). Urinary osmolality, urinary AQP2 and cyclic adenosine monophosphate (cAMP) levels were measured following overnight fluid deprivation and after the administration of 40 g of dDAVP. Baseline values were compared with results after 4 weeks of lithium therapy.

Results

Four weeks of lithium therapy reduced dDAVP-stimulated urinary concentrating ability (996 plusminus 27 to 945 26 mOsm/kg) (P < 0.05) and this was associated with significant reduction in urinary AQP2 excretion (99.2 10.0 to 77.8 7.4 fmol/mol creatinine) (P < 0.05) and urinary cAMP excretion (3188 376 to 2212 378 units) (P < 0.01).

Conclusion

Four weeks of lithium therapy in healthy volunteers produced a small but significant reduction in dDAVP-stimulated urinary concentrating ability, which appears to be mediated by the inhibition of AVP-stimulated translocation of cytoplasmic AQP2 to the collecting tubule apical membrane via inhibition of adenyl cyclase.

Keywords:

lithium, urinary aquaporin 2, human studies, urinary concentrating ability

Clinical Nephrology – Epidemiology – Clinical Trials