Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease (CKD) as a risk factor

NDT Plus Pub Date : 2023-09-18 DOI:10.1093/ckj/sfad241
Sophie Liabeuf, Vesna Pesic, Goce Spasovski, Romaldas Maciulaitis, Mickaël Bobot, Ana Farinha, Carsten A Wagner, Robert J Unwin, Giovambattista Capasso, Inga Arune Bumblyte, Gaye Hafez, Giovambattista Capasso, Alexandre Andrade, Maie Bachmann, Inga Bumblyte, Adrian Constantin Covic, Pilar Delgado, Nicole Endlich, Andreas Engvig, Denis Fouque, Casper Franssen, Sebastian Frische, Liliana Garneata, Loreto Gesualdo, Konstantinos Giannakou, Dimitrios Goumenos, Ayşe Tuğba Kartal, Sophie Liabeuf, Laila-Yasmin Mani, Hans-Peter Marti, Christopher Mayer, Rikke Nielsen, Vesna Pešić, Merita Rroji (Molla), Giorgos Sakkas, Goce Spasovski, Kate Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris Zacharia, Ana Carina Ferreira, Jolanta Malyszko, Ewout Hoorn, Andreja Figurek, Robert Unwin, Carsten Wagner, Christoph Wanner, Annette Bruchfeld, Marion Pepin, Andrzej Wiecek, Dorothea Nitsch, Ivo Fridolin, Gaye Hafez, Maria José Soler Romeo, Michelangela Barbieri, Bojan Batinić, Laura Carrasco, Sol Carriazo, Ron Gansevoort, Gianvito Martino, Francesco Mattace Raso, Ionut Nistor, Alberto Ortiz, Giuseppe Paolisso, Daiva Rastenytė, Gabriel Stefan, Gioacchino Tedeschi, Ziad Massy, Boris Bikbov, Karl Hans Endlich, Olivier Godefroy, Anastassia Kossioni, Justina Kurganaite, Norberto Perico, Giuseppe Remuzzi, Tomasz Grodzicki, Francesco Trepiccione, Carmine Zoccali, Mustafa Arici, Peter Blankestijn, Kai-Uwe Eckardt, Danilo Fliser, Eugenio Gutiérrez Jiménez, Maximilian Konig, Ivan Rychlik, Michela Deleidi, George Reusz, Michele Farisco, Norberto Perico, Pedro Imenez Silva, Mickaël Bobot, Aleksandra Golenia, Alessandra Perna, Alma Idrizi, Brian Hansen, Mariadelina Simeoni
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Abstract

ABSTRACT People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood–brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.
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对认知功能有负面影响的药物(第一部分):慢性肾脏疾病(CKD)是一个危险因素
慢性肾脏疾病(CKD)患者经常患有轻度认知障碍和/或其他神经认知障碍。本综述将分两部分重点介绍CKD患者中导致认知障碍的药物不良反应作为潜在可改变的危险因素。许多CKD患者有大量的合并症,导致多种药物治疗。最近的一项研究发现,肾病学家看到的患者是最复杂的治疗,因为他们有大量的合并症和药物。由于多种用药,这些患者可能会出现广泛的药物不良反应。随着CKD的进展,尿毒症毒素的积累可能导致血脑屏障(BBB)破坏和药代动力学改变,增加影响中枢神经系统(CNS)不良反应的风险。在透析患者中,依赖于肾功能的药物的排泄严重减少,除非调整剂量,否则药物或其代谢物的不良和毒性水平可能在相对低的剂量下达到。第一篇综述将讨论CKD是如何通过(i) CKD相关的血脑屏障破坏和(ii)肾功能降低和透析本身对药物药代动力学的影响来影响中枢神经系统的药物不良反应的危险因素。
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