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Öğe Chemotherapy-related cognitive impairment and kidney dysfunction(2025) Simeoni, Mariadelina; Mulholland, Michele M.; Workeneh, Biruh T.; Capasso, Anna; Capasso, Anna; Hafez, Gaye; Liabeuf, Sophie; Malyszko, Jolanta; Mani, Laila-Yasmin; Trevisani, Francesco; De, Ananya; Wagner, Carsten A.; Massy, Ziad A.; Unwin, Robert; Capasso, Giovambattista; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaboratorsCancer and kidney diseases (KD) intersect in many ways resulting in worse outcomes. Both conditions are correlated with cognitive impairment, which can be exacerbated in cancer patients by known effects of many antineoplastic drugs on cognition, leading to a phenomenon known as chemotherapy-related cognitive impairment (CRCI). This manifests as poor attention span, disturbed short-term memory, and general mental sluggishness. This literature review explores CRCI and investigates the potential impact of KD on this phenomenon. Additionally, we highlight the shared pathogenetic mechanisms (including neurotoxicity, neuroinflammation, oxidative stress, vascular disease, electrolyte, and acid-base imbalances), clinical presentation and imaging findings between cognitive impairment in KD and CRCI. The disruption of the blood-brain barrier might be a key mechanism for increased brain permeability to anticancer drugs in nephropathic patients with cancer. Based on existing knowledge, we found a potential for heightened neurotoxicity of antineoplastic drugs and a synergistic potentiation of cognitive impairment in cancer patients with KD. However, further translational research is urgently required to validate this hypothesis.Öğe Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?(Nephrol Dial Transplant, 2021) Pepin, Marion; Franssen, Casper F.M; Viggiano, Davide; Carriazo, Sol; Gansevoort, Ron T.; Gesualdo, Loreto; Malyszko, Jolanta; Mayer, Christopher; Nitsch, Dorothea; Ortiz, Alberto; Pesic, Vesna; Wiecek, Andrzej; Massy, Ziad A.; (Cognitive Decline in Nephro-Neurology European Cooperative TargetChronic 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.Öğe 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) collaboratorsChronic 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.Öğe Drugs with a negative impact on cognitive functions (Part 2): drug classes to consider while prescribing in CKD patients(2023) Hafez, Gaye; Malyszko, Jolanta; Golenia, Aleksandra; Klimkowicz-Mrowiec, Aleksandra; Ferreira, Ana Carina; Arıcı, Mustafa; Bruchfeld, Annette; Nitsch, Dorothea; Massy, Ziad A.; Pepin, Marion; Capasso, Giovambattista; Mani, Laila-Yasmin; Liabeuf, SophieThere is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood-brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects.Öğe Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease(2024) Liabeuf, Sophie; Hafez, Gaye; Pesic, Vesna; Spasovski, Goce; Bobot, Mickael; Maciulaitis, Romaldas; Bumblyte, Inga Arune; Ferreira, Ana Carina; Farinha, Ana; Malyszko, Jolanta; Pepin, Marion; Massy, Ziad A.; Unwin, Robert; Capasso, Giovambattista; Mani, Laila-Yasmin; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target)The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood-brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain-gut-kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain-gut-kidney axis.Öğe Efficacy of erythropoietin as a neuroprotective agent in CKD-associated cognitive dysfunction: A literature systematic review(2024) Barbieri, Michelangela; Chiodini, Paolo; Di Gennaro, Piergiacomo; Hafez, Gaye; Liabeuf, Sophie; Malyszko, Jolanta; Mani, Laila-Yasmin; Raso, Francesco Mattace; Pepin, Marion; Perico, Norberto; Simeoni, Mariadelina; Zoccali, Carmine; Tortorella, Giovanni; Capuano, Annalisa; Remuzzi, Giuseppe; Capasso, Giovambattista; Paolisso, Giuseppe; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaboratorsPatients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment.Öğe Genetic and circulating biomarkers of cognitive dysfunction and dementia in CKD(2025) Zoccali, Carmine; Mallamaci, Francesca; Wagner, Carsten A.; Unwin, Robert; Nedergaard, Maiken; Hafez, Gaye; Malyszko, Jolanta; Pepin, Marion; Massy, Ziad; Paolisso, Giuseppe; Remuzzi, Giuseppe; Capasso, Giovambattista B.; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaboratorsChronic kidney disease (CKD) is commonly accompanied by cognitive dysfunction and dementia, which, in turn, increase the risk of hospitalization, cardiovascular events and death. Over the last 30 years, only four studies focused on genetic markers of cognitive impairment in CKD and kidney failure (KF), indicating a significant gap in research. These studies suggest potential genetic predispositions to cognitive decline in CKD patients but also underscore the necessity for more comprehensive studies. Seventeen reports have established connections between cognitive function and kidney disease markers such as estimated glomerular filtration rate (eGFR), Cystatin C and albuminuria. A rapid eGFR decline has been associated with cognitive deterioration and vascular dementia, and mild to moderate eGFR reductions with diminished executive function in elderly men. Various biomarkers have been associated to Alzheimer’s disease or dementia in CKD and KF. These include amyloid beta and phosphorylated tau proteins, uremic toxins, gut microbiota, metabolic indicators, hypertension, endothelial dysfunction, vitamins and inflammation. However, the causal relevance of these associations remains unclear. Overall, the available evidence points to a complex interplay between the different biomarkers and cognitive health in CKD patients, underscoring the need for more research to elucidate these relationships.Öğe Methodological challenges and biases in the field of cognitive function among patients with chronic kidney disease(Frontiers Media SA, 2023) Giannakou, Konstantinos; Golenia, Aleksandra; Liabeuf, Sophie; Malyszko, Jolanta; Mattace-Raso, Francesco; Farinha, Ana; Spasovski, Goce; Hafez, Gaye; Wiecek, Andrzej; Capolongo, Giovanna; Capasso, Giovambattista; Massy, Ziad A.Chronic kidney disease (CKD) affects approximately 850 million people globally and is associated with an increased risk of cognitive impairment. The prevalence of cognitive impairment among CKD patients ranges from 30 to 60%, and the link between CKD and cognitive impairment is partially understood. Methodological challenges and biases in studying cognitive function in CKD patients need to be addressed to improve diagnosis, treatment, and management of cognitive impairment in this population. Here, we review the methodological challenges and study design issues, including observational studies’ limitations, internal validity, and different types of bias that can impact the validity of research findings. Understanding the unique challenges and biases associated with studying cognitive function in CKD patients can help to identify potential sources of error and improve the quality of future research, leading to more accurate diagnoses and better treatment plans for CKD patients.
