Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?
Sophie Liabeuf, Marion Pépin, Casper Franssen, Davide Viggiano, Sol Carriazo, Ron T. Gansevoort, Loreto Gesualdo, Gaye Hafez, Jolanta Małyszko, Christopher Mayer, Dorothea Nitsch, Alberto Ortíz, Vesna Pešić, Andrzej Więcek, Ziad A. Massy, CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target), Giovambattista Capasso, Alexandre Andrade, Maie Bachmann, Inga Arūnė Bumblytė, Adrian Covic, Pilar Delgado, Nicole Endlich, Andreas Engvig, Denis Fouque, Casper Franssen, Sebastian Frische, Liliana Gârneaţă, Loreto Gesualdo, Konstantinos Giannakou, Dimitrios Goumenos, Ayşe Tuğba Kartal, Laila‐Yasmin Mani, Hans-Peter Marti, Christopher Mayer, Rikke Nielsen, Vesna Pešić, Merita Rroji, Giorgos K. Sakkas, Goce Spasovski, Kate Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris C. Zacharia, Ana Carina Ferreira, Jolanta Malyszko, Ewout J. Hoorn, Andreja Figurek, Robert J. Unwin, Carsten A. Wagner, Christoph Wanner, Annette Bruchfeld, Marion Pépin, Andrzej Więcek, Dorothea Nitsch, Ivo Fridolin, Gaye Hafez, María José Soler Romeo, Michelangela Barbieri, Bojan Batinić, Laura Carrasco, Sol Carriazo, Ron T. Gansevoort, Gianvito Martino, Francesco Mattace‐Raso, Ionuţ Nistor, Alberto Ortíz, Giuseppe Paolisso, Daiva Rastenytė, Gabriel Ştefan, Gioacchino Tedeschi, Ziad A. Massy, Boris Bikbov, Karlhans Endlich, Olivier Godefroy, Jean‐Marc Chillon, Anastassia Kossioni, Justina Kurganaite, Norberto Perico, Giuseppe Remuzzi, Tomasz Grodzicki, Francesco Trepiccione, Carmine Zoccali, Mustafa Arıcı, Peter J. Blankestijn, Kai‐Uwe Eckardt, Danilo Fliser, Eugenio Gutiérrez Jiménez, Maximilian König, Ivan Rychlík, Michela Deleidi, György Reusz
Abstract
Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care.