Brain dysfunction in tubular and tubulointerstitial kidney diseases
Authors: Viggiano Davide , Bruchfeld Annette , Carriazo Sol , de Donato Antonio , Endlich Nicole , Ferreira Ana Carina , Figurek Andreja , Fouque Denis , Franssen Casper F M , Giannakou Konstantinos , Goumenos Dimitrios , Hoorn Ewout J , Nitsch Dorothea , Ortiz Alberto , Pešić Vesna , Rastenyté Daiva , Soler Maria José , Rroji Merita , Trepiccione Francesco , Unwin Robert J , Wagner Carsten A , Wieçek Andrzej , Zacchia Miriam , Zoccali Carmine , Capasso Giovambattista ,   the 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 , Mani Laila-Yasmin , Marti Hans-Peter , Mayer Christopher , Nielsen Rikke , Pšić Vesna , Rroji (Molla) Merita , Sakkas Giorgos , Spasovski Goce , Stevens Kate I , Vazelov Evgueniy , Viggiano Davide , Zacharia Lefteris , Ferreira Ana Carina , Malyszko Jolanta , Hoorn Ewout , Figurek Andreja , Unwin Robert , Wagner Carsten A , Wanner Christoph , Bruchfeld Annette , Pépin Marion , Wieçek Andrzej , Nitsch Dorothea , Fridolin Ivo , Hafez Gaye , Soler Maria José , 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 A , Bikbov Boris , Endlich Karl Hans , Godefroy Olivier , Chillon Jean-Marc , 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 , König Maximilian , Rychlik Ivan , Deleidi Michela , Reusz George 
Published: September 2021

ABSTRACT
Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research.