Procino G, Portincasa P, Mastrofrancesco L, Castorani L, Bonfrate L, Addabbo F, Carmosino M, Di Ciaula A, Svelto M
Department of Biosciences, Biotechnologies & Biopharmaceutics, University of Bari, Bari, Italy.
Clinica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy.
Clin Pharmacol Ther. 2016 May;99(5):528-37. doi: 10.1002/cpt.305. Epub 2016 Jan 12.
We previously reported that statins improve the symptoms of X-linked nephrogenic diabetes insipidus (X-NDI) in animal models. The aim of this study was to verify whether the pleiotropic effect of statins on AQP2 trafficking and kidney-concentrating ability, observed in rodents, was attainable in humans at therapeutic doses. We enrolled 24 naïve hypercholesterolemic patients and measured urine excretion of AQP2 (uAQP2) at baseline and during 12 weeks of treatment with simvastatin 20 mg/day. Simvastatin induced a rapid and significant increase of uAQP2, reduced the 24-hour diuresis, and increased urine osmolality. These effects were also maintained in patients chronically treated with statins for at least 1 year. This study strongly suggests that statins may effectively enhance the efficacy of current pharmacological treatment of patients with urine-concentrating defects caused by defective AQP2 plasma membrane trafficking, like X-NDI.
我们之前报道过，他汀类药物可改善动物模型中X连锁肾性尿崩症（X-NDI）的症状。本研究的目的是验证在啮齿动物中观察到的他汀类药物对水通道蛋白2（AQP2）转运和肾脏浓缩能力的多效性作用，在治疗剂量下是否也能在人类中实现。我们招募了24名未经治疗的高胆固醇血症患者，在基线时以及用辛伐他汀20毫克/天治疗12周期间测量AQP2的尿排泄量（uAQP2）。辛伐他汀使uAQP2迅速且显著增加，减少了24小时尿量，并增加了尿渗透压。这些作用在接受他汀类药物长期治疗至少1年的患者中也得以维持。本研究有力地表明，他汀类药物可能有效增强目前对因AQP2质膜转运缺陷导致尿液浓缩功能缺陷的患者（如X-NDI患者）的药物治疗效果。
