Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor
Authors: Liabeuf Sophie , Pešić Vesna , Spasovski Goce , Maciulaitis Romaldas , Bobot Mickaël , Farinha Ana , Wagner Carsten A , Unwin Robert J , Capasso Giovambattista , Bumblyte Inga Arune , Hafez Gaye ,   CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target), Capasso Giovambattista , Andrade Alexandre , Bachmann Maie , Bumblyte Inga , Covic Adrian Constantin , Delgado Pilar , Endlich Nicole , Engvig Andreas , Fouque Denis , Franssen Casper , Frische Sebastian , Garneata Liliana , Gesualdo Loreto , Giannakou Konstantinos , Goumenos Dimitrios , Kartal Ayşe Tuğba , Liabeuf Sophie , Mani Laila-Yasmin , Marti Hans-Peter , Mayer Christopher , Nielsen Rikke , Pešić Vesna , Rroji (Molla) Merita , Sakkas Giorgos , Spasovski Goce , Stevens Kate , Vazelov Evgueniy , Viggiano Davide , Zacharia Lefteris , Ferreira Ana Carina , Malyszko Jolanta , Hoorn Ewout , Figurek Andreja , Unwin Robert , Wagner Carsten , Wanner Christoph , Bruchfeld Annette , Pepin Marion , Wiecek Andrzej , Nitsch Dorothea , Fridolin Ivo , Hafez Gaye , Romeo Maria José Soler , Barbieri Michelangela , Batinić Bojan , Carrasco Laura , Carriazo Sol , Gansevoort Ron , Martino Gianvito , Raso Francesco Mattace , Nistor Ionut , Ortiz Alberto , Paolisso Giuseppe , Rastenytė Daiva , Stefan Gabriel , Tedeschi Gioacchino , Massy Ziad , Bikbov Boris , Endlich Karl Hans , Godefroy Olivier , Kossioni Anastassia , Kurganaite Justina , Perico Norberto , Remuzzi Giuseppe , Grodzicki Tomasz , Trepiccione Francesco , Zoccali Carmine , Arici Mustafa , Blankestijn Peter , Eckardt Kai-Uwe , Fliser Danilo , Jiménez Eugenio Gutiérrez , Konig Maximilian , Rychlik Ivan , Deleidi Michela , Reusz George , Farisco Michele , Perico Norberto , Silva Pedro Imenez , Bobot Mickaël , Golenia Aleksandra , Perna Alessandra , Idrizi Alma , Hansen Brian , Simeoni Mariadelina 
Published: September 2023

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.