Reply to "Letter to the editor: 'Urothelial barrier dysfunction: cause or outcome of ketamine-induced voiding dysfunction'".
Reply to "Letter to the editor: 'Urothelial barrier dysfunction: cause or outcome of ketamine-induced voiding dysfunction'".
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回复“致编辑的信：‘尿路上皮屏障功能障碍：氯胺酮引起的排尿功能障碍的原因或结果’”。
DOI：
10.1152/ajprenal.00555.2016
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Yu,Weiqun
中科院分区：
文献类型：
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作者：
Yu,Weiqun
主持人：我们要感谢Wang等人。(3)感谢他们对我们文章的关注和评论。自Shahani等人首次报告氯胺酮膀胱炎以来，(2)10年前，这种新的泌尿功能障碍的机制仍然是一个谜。氯胺酮在尿液中蓄积，在重度氯胺酮膀胱炎患者中常见尿路上皮溃疡，这可能是氯胺酮破坏尿路上皮屏障功能并引起氯胺酮膀胱炎的假设的主要原因。最近的几篇文章也表明氯胺酮对尿路上皮细胞的有害影响（1）。尿路上皮细胞形成了我们身体中最紧密的屏障，它允许膀胱暂时储存尿液毒素。最近的研究还表明，尿道上皮的表面细胞是机械感觉的，并且响应于尿液填充和排空而经历戏剧性的膜运输。我们的关键发现是，我们观察到排尿功能障碍的排尿点测定和膀胱测压，但屏障功能是完整的。我们使用足以诱导排尿功能障碍的氯胺酮剂量，但未检测到尿路上皮异常，这表明氯胺酮诱导的排尿功能障碍先于屏障功能障碍的出现。我们确实同意以下评论，即尿路上皮屏障可能在氯胺酮膀胱炎的发病机制中发挥一定作用，使尿液渗漏到膀胱间质中，加重膀胱炎和排尿功能障碍。我们倾向于认为，这种屏障破坏不是由于直接毒性，而更可能是氯胺酮的继发性作用，可能影响机械感觉功能和膜运输。我们还应该记住，氯胺酮膀胱炎患者的其他膀胱组织中存在广泛的病理变化，包括神经元和肌源性。值得注意的是，并非所有患者的屏障功能都受到破坏。因此，我们坚信氯胺酮可能会破坏一些未知的细胞通路，导致膀胱和其他器官发生广泛的病理变化。了解这些氯胺酮影响的信号通路将是治疗氯胺酮膀胱炎的关键。
REPLY: We would like to thank Wang et al.(3) for their interest in and comment on our article. Since the first report of ketamine cystitis by Shahani et al.(2) 10 years ago, the mechanism of this new urinary dysfunction is still a mystery. Ketamine is accumulated in urine, and urothelial ulceration is commonly observed in severe ketamine cystitis patients, which might be the major reason for the hypothesis that ketamine disrupts urothelial barrier function and causes ketamine cystitis. Several recent articles also indicate a detrimental effect of ketamine on urothelial cells (1). Urothelial cells form the tightest barrier in our body, which allows the bladder to temporarily store urine toxins. Recent research also indicates that the superficial cells of the urothelium are mechanosensory and undergo dramatic membrane trafficking in response to urine filling and emptying. Our key finding is that we observed voiding dysfunction by voiding spot assay and cystometrogram, but the barrier function is intact. We used a ketamine dosage that was sufficient to induce voiding dysfunction, but no urothelial abnormality could be detected, which indicates that ketamine-induced voiding dysfunction precedes the emergence of barrier dysfunction. We do agree with the comment that the urothelial barrier likely plays some role in the pathogenesis of ketamine cystitis, allowing urine to leak into the bladder interstitial spaces and aggravate the cystitis and voiding dysfunction. We tend to believe that this disrupted barrier is not due to direct toxicity, but is more likely a secondary effect of ketamine, affecting perhaps mechanosensory function and membrane trafficking. We also should bear in mind that there are extensive pathological changes in the other bladder tissues of ketamine cystitis patients, including neuronal and myogenic. It is also worth noting that not all patients have disrupted barrier function. We therefore strongly believe that ketamine might disrupt some yet unknown cellular pathways which causes extensive pathological changes in the bladder and also other organs. Understanding these ketamineaffected signal pathways will be critical for the treatment of ketamine cystitis.