Effects of chronic lithium administration on renal acid excretion in humans and rats.
Effects of chronic lithium administration on renal acid excretion in humans and rats.
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DOI：
10.14814/phy2.12242
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发表时间：
2014-12-01
影响因子：
2.5
通讯作者：
Walker RJ
中科院分区：
文献类型：
--
作者：
Weiner ID;Leader JP;Bedford JJ;Verlander JW;Ellis G;Kalita P;Vos F;de Jong S;Walker RJ
锂治疗最常见的影响肾脏的副作用是肾源性尿崩症（NDI）和慢性肾脏疾病。锂也可能诱发远端肾小管酸中毒。本研究调查了慢性锂暴露对肾脏酸碱平衡的影响，重点是氨和柠檬酸盐排泄。我们将11名长期锂治疗的患者与6名健康人进行了比较。在基础条件下，锂治疗的个体比对照受试者排出更多的尿氨。急性酸负荷后，锂处理和对照组的尿氨排泄量均增加约两倍，高于基础速率。锂治疗受试者和对照受试者的尿pH值或尿柠檬酸盐排泄量无显著差异。为了阐明可能的机制，将大鼠随机分配至含锂饮食或常规饮食6个月。与人类相似，锂处理大鼠的基础氨排泄量显著较高;此外，尿柠檬酸盐排泄量也显著较高。尿液pH值无差异。锂处理大鼠中关键氨转运蛋白恒河猴C糖蛋白（Rhcg）的表达显著高于对照大鼠。我们的结论是，慢性锂暴露增加肾氨排泄的机制独立于尿pH值，并可能涉及通过氨转运蛋白，Rhcg增加集合管氨分泌。本研究调查了慢性锂暴露对肾脏酸碱平衡的影响，重点是氨和柠檬酸盐排泄。慢性锂暴露通过与尿pH无关的机制增加肾氨排泄，可能涉及通过氨转运蛋白Rhcg增加集合管氨分泌。
Lithium therapy's most common side effects affecting the kidney are nephrogenic diabetes insipidus (NDI) and chronic kidney disease. Lithium may also induce a distal renal tubular acidosis. This study investigated the effect of chronic lithium exposure on renal acid–base homeostasis, with emphasis on ammonia and citrate excretion. We compared 11 individuals on long‐term lithium therapy with six healthy individuals. Under basal conditions, lithium‐treated individuals excreted significantly more urinary ammonia than did control subjects. Following an acute acid load, urinary ammonia excretion increased approximately twofold above basal rates in both lithium‐treated and control humans. There were no significant differences between lithium‐treated and control subjects in urinary pH or urinary citrate excretion. To elucidate possible mechanisms, rats were randomized to diets containing lithium or regular diet for 6 months. Similar to humans, basal ammonia excretion was significantly higher in lithium‐treated rats; in addition, urinary citrate excretion was also significantly greater. There were no differences in urinary pH. Expression of the critical ammonia transporter, Rhesus C Glycoprotein (Rhcg), was substantially greater in lithium‐treated rats than in control rats. We conclude that chronic lithium exposure increases renal ammonia excretion through mechanisms independent of urinary pH and likely to involve increased collecting duct ammonia secretion via the ammonia transporter, Rhcg. This study investigated the effect of chronic lithium exposure on renal acid–base homeostasis, with emphasis on ammonia and citrate excretion. Chronic lithium exposure increases renal ammonia excretion through mechanisms independent of urinary pH and likely to involve increased collecting duct ammonia secretion via the ammonia transporter, Rhcg.