Liabeuf Sophie, Hafez Gaye, Pešić Vesna, Spasovski Goce, Bobot Mickaël, Mačiulaitis Romaldas, Bumblyte Inga Arune, Ferreira Ana Carina, Farinha Ana, Malyszko Jolanta, Pépin Marion, Massy Ziad A, Unwin Robert, Capasso Giovambattista, Mani Laila-Yasmin
Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France.
MP3CV Laboratory, EA7517, Jules Verne University of Picardie, Amiens, France.
Clin Kidney J. 2024 Jun 14;17(8):sfae174. doi: 10.1093/ckj/sfae174. eCollection 2024 Aug.
The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood-brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain-gut-kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain-gut-kidney axis.
近年来,慢性肾脏病(CKD)与认知功能之间的关系受到了越来越多的关注。由于CKD患者对感染的易感性增加,抗菌药物(ABs)是其治疗方案的关键组成部分。在我们对CKD患者长期用药的神经认知影响进行综述研究之后,我们建议关注ABs对认知功能的直接和间接影响。由于药物药代动力学改变、肾小球滤过率下降以及血脑屏障可能被破坏,CKD患者易发生药物不良反应(ADR)。ABs已被确定为脆弱患者群体中ADR的主要原因。本综述探讨了AB类药物(如β-内酰胺类、氟喹诺酮类、氨基糖苷类和甲硝唑)对CKD患者中枢神经系统(CNS)的直接神经毒性作用。我们将主要关注与ABs相关的对CNS的急性影响,因为它们是在CKD患者中研究最广泛的影响。此外,该综述还描述了ABs对肠道微生物群的调节作用,这可能会影响CNS症状。复杂的脑-肠-肾轴成为一个关键焦点,揭示了ABs诱导的微生物群改变与CKD患者CNS表现之间的相互作用。接受静脉AB治疗的CKD患者中抗生素相关性脑病的患病率支持对ABs进行治疗药物监测,以减少该患者群体中ADR的数量和严重程度。总之,要阐明ABs对CKD患者认知功能的影响,需要全面了解并制定针对药代动力学改变和脑-肠-肾轴的个性化治疗策略。