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    Albuminuria as a risk factor for mild cognitive impairment and dementia—what is the evidence?
    (Nephrol Dial Transplant, 2021) Bikbov, Boris; Soler, Maria Jose; Pesic, Vesna; Capasso, Giovambattista; Unwin, Robert; Endres, Matthias; Remuzzi, Giuseppe; Perico, Norberto; Gansevoort, Ron; Mattace-Raso, Francesco; Bruchfeld, Annette; Figurek, Andreja; (Cognitive Decline in Nephro-Neurology European Cooperative Target; Hafez, Gaye
    Kidney dysfunction can profoundly influence many organ systems, and recent evidence suggests a potential role for increased albuminuria in the development of mild cognitive impairment (MCI) or dementia. Epidemiological studies conducted in different populations have demonstrated that the presence of increased albuminuria is associated with a higher relative risk of MCI or dementia both in cross-sectional analyses and in studies with long-term follow-up. The underlying pathophysiological mechanisms of albuminuria’s effect are as yet insufficiently studied, with several important knowledge gaps still present in a complex relationship with other MCI and dementia risk factors. Both the kidney and the brain have microvascular similarities that make them sensitive to endothelial dysfunction involving different mechanisms, including oxidative stress and inflammation. The exact substrate of MCI and dementia is still under investigation, however available experimental data indicate that elevated albuminuria and low glomerular filtration rate are associated with significant neuroanatomical declines in hippocampal function and grey matter volume. Thus, albuminuria may be critical in the development of cognitive impairment and its progression to dementia. In this review, we summarize the available evidence on albuminuria’s link to MCI and dementia, point to existing gaps in our knowledge and suggest actions to overcome them. The major question of whether interventions that target increased albuminuria could prevent cognitive decline remains unanswered. Our recommendations for future research are aimed at helping to plan clinical trials and to solve the complex conundrum outlined in this review, with the ultimate goal of improving the lives of patients with chronic kidney disease.
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    Animal models to study cognitive impairment of chronic kidney disease
    (2024) Silva, Pedro H. Imenez; Pepin, Marion; Figurek, Andreja; Gutierrez-Jimenez, Eugenio; Bobot, Mickael; Iervolino, Anna; Mattace-Rosso, Francesco; Hoorn, Ewout J.; Bailey, Matthew A.; Henaut, Lucie; Nielsen, Rikke; Frische, Sebastian; Trepiccione, Francesco; Hafez, Gaye; Altunkaynak, Hande O.; Endlich, Nicole; Unwin, Robert; Capasso, Giovambattista; Pesic, Vesna; Massy, Ziad; Wagner, Carsten A.; Consortium, Connect
    Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD) and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives and society. However, the underlying pathomechanisms are poorly understood and current therapies mostly aim at supporting patients in their daily life. This illustrates the urgent need to elucidate the pathogenesis, and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modelling of cognitive disorders in CKD. We discuss the use of mice, rats and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving therapy of people with CKD and MCI.
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    Cognitive impairment in kidney transplanted patients
    (2025) Malyszko, Jolanta; Golenia, Aleksandra; Farisco, Michele; Lo Re, Vincenzina; Klimkowicz-Mrowiec, Aleksandra; Capasso, Giovambattista; Goumenos, Dimitris; Rroji, Merita; Figurek, Andreja; Hafez, Gaye; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaborators
    Chronic kidney disease affects almost all of the organs. Recently, more attention has been paid to the kidney and the central nervous system connections. In patients on kidney replacement therapy, including kidney transplantation, there is an increased prevalence of cognitive impairment, and depression and other neurological complications, such as cerebrovascular disorders and movement disorders. Kidney transplant recipients need an assessment for the risk factors and the pattern of cognitive impairment (memory, attention and executive function decline). This enables an accurate diagnosis to be made at an earlier stage. Partial post-transplant cognitive impairment recovery is also important. Finally, doctors and patients alike face numerous ethical concerns and challenges regarding the transplantation of kidneys and other solid organs. In this review, we examined some key issues regarding cognitive impairment in kidney transplant patients. We focused on the mechanism of cognitive impairment in kidney transplant recipients, patterns of cognitive impairment; evaluation of patients with cognitive impairment for kidney transplantation, the potential impact of cognitive impairment on waitlisted and transplanted patients on patient care, non-pharmacological interventions and unmet medical needs, psychological and ethical issues in kidney transplantation, and unmet needs. As cognitive impairment in kidney transplant recipients is an underestimated, underrecognized but clinically relevant problem, screening for cognitive function before and after kidney transplantation would be worth considering in standard routine practice.