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 microg 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 +/- 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/micromol creatinine) (P < 0.05) and urinary cAMP excretion (3188 +/- 376 to 2212 +/- 378 units) (P < 0.01).


CONCLUSIONS
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.
Walker
Robert J
RJ
Department of Medical & Surgical Sciences, University of Otago, Dunedin, New Zealand. rob.walker@stonebow.otago.ac.nz
Weggery
Susan
S
Bedford
Jennifer J
JJ
McDonald
Fiona J
FJ
Ellis
Gaye
G
Leader
John P
JP
D000067956:Adenylyl Cyclase Inhibitors; D000328:Adult; D051399:Aquaporin 2; D020346:Aquaporins / Q000652:urine*; D001693:Biological Transport, Active / Q000187:drug effects; D000242:Cyclic AMP / Q000652:urine; D003894:Deamino Arginine Vasopressin; D005260:Female; D006801:Humans; D007671:Kidney Concentrating Ability / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism; D016651:Lithium Carbonate / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014868:Water Deprivation / Q000502:physiology
C496023:AQP2 protein, human; D000067956:Adenylyl Cyclase Inhibitors; D051399:Aquaporin 2; D020346:Aquaporins; D016651:Lithium Carbonate; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin