Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?

Author:

Liabeuf Sophie12ORCID,Pepin Marion34,Franssen Casper F M5,Viggiano Davide6,Carriazo Sol7ORCID,Gansevoort Ron T5,Gesualdo Loreto8,Hafez Gaye9ORCID,Malyszko Jolanta10,Mayer Christopher11,Nitsch Dorothea12,Ortiz Alberto7ORCID,Pešić Vesna13,Wiecek Andrzej14,Massy Ziad A315,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,Pešić Vesna,Rroji 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,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,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,Konig Maximilian,Rychlik Ivan,Deleidi Michela,Reusz George,

Affiliation:

1. Department of Pharmacology, Amiens University Medical Center, Amiens, France

2. MP3CV Laboratory, EA7517, University of Picardie Jules Verne, Amiens, France

3. Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Villejuif, France

4. Department of Geriatrics, Ambroise Paré University Medical Center, APHP, Boulogne-Billancourt, France

5. Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

6. Department of Nephrology, University of Campania “Luigi Vanvitelli”, Naples, Italy

7. Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, Madrid, Spain

8. Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari, Italy

9. Department of Pharmacology, Faculty of Pharmacy, Altinbas University, Istanbul, Turkey

10. Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland

11. Center for Health and Bioresources, Biomedical Systems, AIT Austrian Institute of Technology, Vienna, Austria

12. Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK

13. Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

14. Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, in Katowice, Katowice, Poland

15. Department of Nephrology, Ambroise Paré University Medical Center, APHP, Boulogne-Billancourt/Paris, France

Abstract

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.

Funder

COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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