Acidosis, cognitive dysfunction and motor impairments in patients with kidney disease
Pedro Henrique Imenez Silva, Robert J. Unwin, Ewout J. Hoorn, Alberto Ortíz, Francesco Trepiccione, Rikke Nielsen, Vesna Pešić, Gaye Hafez, Denis Fouque, Ziad A. Massy, Chris I. De Zeeuw, Giovambattista Capasso, Carsten A. Wagner, 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 I Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris C. Zacharia, Ana Carina Ferreira, Jolanta Małyszko, Ewout J. Hoorn, Andreja Figurek, Robert 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
Metabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10-30% of patients with advanced stages of CKD. Likewise, in patients with a kidney transplant, prevalence rates of metabolic acidosis range from 20% to 50%. CKD has recently been associated with cognitive dysfunction, including mild cognitive impairment with memory and attention deficits, reduced executive functions and morphological damage detectable with imaging. Also, impaired motor functions and loss of muscle strength are often found in patients with advanced CKD, which in part may be attributed to altered central nervous system (CNS) functions. While the exact mechanisms of how CKD may cause cognitive dysfunction and reduced motor functions are still debated, recent data point towards the possibility that acidosis is one modifiable contributor to cognitive dysfunction. This review summarizes recent evidence for an association between acidosis and cognitive dysfunction in patients with CKD and discusses potential mechanisms by which acidosis may impact CNS functions. The review also identifies important open questions to be answered to improve prevention and therapy of cognitive dysfunction in the setting of metabolic acidosis in patients with CKD.