Bedford Jennifer J, Weggery Susan, Ellis Gaye, McDonald Fiona J, Joyce Peter R, Leader John P, Walker Robert J
Department of Medical & Surgical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand.
Clin J Am Soc Nephrol. 2008 Sep;3(5):1324-31. doi: 10.2215/CJN.01640408. Epub 2008 Jul 2.
Polyuria, polydipsia, and nephrogenic diabetes insipidus have been associated with use of psychotropic medications, especially lithium.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The impact of psychotropic medications on urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion was investigated after overnight fluid deprivation, and over 6 h after 40 microg of desmopressin (dDAVP), in patients on lithium (n = 45), compared with those on alternate psychotropic medications (n = 42).
Those not on lithium demonstrated normal urinary concentrating ability (958 +/- 51 mOsm/kg) and increased urinary excretion of AQP2 (98 +/- 21 fmol/micromol creatinine) and cAMP (410 +/- 15 pmol/micromol creatinine). Participants taking lithium were divided into tertiles according to urinary concentrating ability: normal, >750 mOsm/kg; partial nephrogenic diabetes insipidus (NDI), 750 to 300 mOsm/kg; full NDI, <300 mOsm/kg. Urinary AQP2 concentrations were 70.9 +/- 13.6 fmol/micromol creatinine (normal), 76.5 +/- 10.4 fmol/micromol creatinine (partial NDI), and 27.3 fmol/micromol creatinine (full NDI). Impaired urinary concentrating ability and reduced urinary AQP2, cAMP excretion correlated with duration of lithium therapy. Other psychotropic agents did not impair urinary concentrating ability. Eleven patients on lithium were enrolled in a randomized placebo-controlled crossover trial investigating the actions of amiloride (10 mg daily for 6 wk) on dDAVP-stimulated urinary concentrating ability and AQP2 excretion. Amiloride increased maximal urinary osmolality and AQP2 excretion.
By inference, amiloride-induced reduction of lithium uptake in the principal cells of the collecting duct improves responsiveness to AVP-stimulated translocation of AQP2 to the apical membrane of the principal cells.
多尿、烦渴和肾性尿崩症与使用精神药物有关，尤其是锂盐。
设计、地点、参与者与测量方法：在过夜禁水后以及给予40微克去氨加压素（dDAVP）6小时后，对服用锂盐的患者（n = 45）和服用其他精神药物的患者（n = 42）进行研究，观察精神药物对尿浓缩能力和尿水通道蛋白2（AQP2）排泄的影响。
未服用锂盐的患者尿浓缩能力正常（958±51毫渗量/千克），尿AQP2排泄增加（98±21飞摩尔/微摩尔肌酐），cAMP排泄增加（410±15皮摩尔/微摩尔肌酐）。服用锂盐的参与者根据尿浓缩能力分为三分位数：正常，>750毫渗量/千克；部分肾性尿崩症（NDI），750至300毫渗量/千克；完全NDI，<300毫渗量/千克。尿AQP2浓度分别为70.9±13.6飞摩尔/微摩尔肌酐（正常）、76.5±10.4飞摩尔/微摩尔肌酐（部分NDI）和27.3飞摩尔/微摩尔肌酐（完全NDI）。尿浓缩能力受损以及尿AQP2、cAMP排泄减少与锂盐治疗时间相关。其他精神药物未损害尿浓缩能力。11名服用锂盐的患者参加了一项随机安慰剂对照交叉试验，研究氨氯地平（每日10毫克，共6周）对dDAVP刺激的尿浓缩能力和AQP2排泄的作用。氨氯地平增加了最大尿渗透压和AQP2排泄。
由此推断，氨氯地平减少集合管主细胞对锂的摄取，从而改善了对AVP刺激的AQP2向主细胞顶端膜转运的反应性。
