Aminoglycoside-induced nephrotoxicity in children.
Aminoglycoside-induced nephrotoxicity in children.
复制标题
DOI：
10.1007/s00467-016-3533-z
复制
发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Pirmohamed M
中科院分区：
文献类型：
--
作者：
McWilliam SJ;Antoine DJ;Smyth RL;Pirmohamed M
氨基糖苷类抗生素，特别是庆大霉素和妥布霉素，仍常用于儿科临床实践。这些药物引起肾毒性，其特别影响近端小管上皮细胞，这是由于通过多配体受体巨蛋白的氨基糖苷类的选择性内吞作用和积累。最近的流行病学研究，使用更广泛接受的急性肾损伤（阿基）定义，表明阿基可能发生在20%至33%的氨基糖苷类药物暴露儿童中。最近发表了一套关于氨基糖苷类药物诱导肾毒性的表型标准。这些是专门为药物基因组学研究提供强大的表型分析而设计的，但它们可以为所有临床研究的标准化铺平道路。新型肾脏生物标志物，特别是肾损伤分子-1，比传统标志物更早识别氨基糖苷类药物诱导的近端肾小管损伤，并在观察性研究中显示出前景。进一步的研究需要证明与临床相关结果的明确关联，以告知转化为临床实践。延长氨基糖苷类药物给药间隔可降低肾毒性，但其使用需要更广泛。他汀类药物对巨蛋白介导的内吞作用的抑制代表了一种预防氨基糖苷类药物诱导的肾毒性的新方法，目前正在临床试验中进行评估。对今后的发展方向提出了建议。
Aminoglycoside antibiotics, in particular gentamicin and tobramycin, are still commonly used in paediatric clinical practice. These drugs cause nephrotoxicity, which particularly affects the proximal tubule epithelial cells due to selective endocytosis and accumulation of aminoglycosides via the multi-ligand receptor megalin. Recent epidemiological studies, using more widely accepted definitions of acute kidney injury (AKI), have suggested that AKI may occur in between 20 and 33 % of children exposed to aminoglycosides. A consensus set of phenotypic criteria for aminoglycoside-induced nephrotoxicity have recently been published. These are specifically designed to provide robust phenotyping for pharmacogenomic studies, but they can pave the way for standardisation for all clinical studies. Novel renal biomarkers, in particular kidney injury molecule-1, identify aminoglycoside-induced proximal tubular injury earlier than traditional markers and have shown promise in observational studies. Further studies need to demonstrate a clear association with clinically relevant outcomes to inform translation into clinical practice. Extended interval dosing of aminoglycosides results in a reduction in nephrotoxicity, but its use needs to become more widespread. Inhibition of megalin-mediated endocytosis by statins represents a novel approach to the prevention of aminoglycoside-induced nephrotoxicity which is currently being evaluated in a clinical trial. Recommendations for future directions are provided.
登录
查看更多内容
DOI：
10.1111/j.1365-2125.1995.tb05719.x
发表时间：
1995-06-01
影响因子：
3.4
作者：
BEGG, EJ;BARCLAY, ML;DUFFULL, SB
通讯作者：
DUFFULL, SB
影响因子：
5.2
作者：
Coulthard, Kingsley P.;Peckham, Daniel G.;Turnidge, John
通讯作者：
Turnidge, John
影响因子：
3.1
作者：
Hoffmann, IM;Rubin, BK;Bitzan, MM
通讯作者：
Bitzan, MM
影响因子：
19.6
作者：
Goldstein, Stuart L.;Mottes, Theresa;Kirkendall, Eric S.
通讯作者：
Kirkendall, Eric S.
影响因子：
19.6
作者：
Akcan-Arikan, A.;Zappitelli, M.;Goldstein, S. L.
通讯作者：
Goldstein, S. L.