Faculty of Medicine

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Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease
(Oxford University Press (OUP), 2024-08)
Liabeuf, Sophie
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Hafez, Gaye
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Pešić, Vesna
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Bobot, Mickaël
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.
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Cognitive impairment in CKD patients: a guidance document by the CONNECT network
(Oxford University Press (OUP), 2024-09)
Bolignano, Davide
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Simeoni, Mariadelina
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Hafez, Gaye
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Pepin, Marion
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Gallo, Antonio
Cognitive impairment is a prevalent and debilitating complication in patients with chronic kidney disease (CKD). This position paper, developed by the Cognitive Decline in Nephro-Neurology: European Cooperative Target network, provides guidance on the epidemiology, risk factors, pathophysiology, diagnosis and clinical management of CKD-related cognitive impairment. Cognitive impairment is significantly more common in CKD patients compared with the general population, particularly those undergoing haemodialysis. The development of cognitive impairment is influenced by a complex interplay of factors, including uraemic neurotoxins, electrolytes and acid-base disorders, anaemia, vascular damage, metabolic disturbances and comorbidities like diabetes and hypertension. Effective screening and diagnostic strategies are essential for early identification of cognitive impairment utilizing cognitive assessment tools, neuroimaging and circulating biomarkers. The impact of various drug classes, including antiplatelet therapy, oral anticoagulants, lipid-lowering treatments and antihypertensive drugs, on cognitive function is evaluated. Management strategies encompass pharmacological and non-pharmacological interventions, with recommendations for optimizing cognitive function while managing CKD-related complications. This guidance highlights the importance of addressing cognitive impairment in CKD patients through early detection, careful medication management and tailored therapeutic strategies to improve patient outcomes.
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Cognitive decline related to chronic kidney disease as an exclusion factor from kidney transplantation: results from an international survey
(Oxford University Press (OUP), 2024-04-13)
Farisco, Michele
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Blumblyte, Inga A
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Franssen, Casper
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Nitsch, Dorothea
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Zecchino, Irene
<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Background and hypothesis</jats:title> <jats:p>There seems to be a lack of consensus on the necessity and the modality of psychological and specifically cognitive assessment of candidates for kidney transplantation. Both points are often delegated to individual hospitals/centres, whereas international guidelines are inconsistent. We think it is essential to investigate professionals' opinions to advance towards a consistent clinical practice.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This paper presents the results of an international survey among clinical professionals, mainly nephrologists from the CONNECT (Cognitive decline in Nephro-Neurology: European Cooperative Target) network and beyond (i.e. from personal contacts of CONNECT members). The survey investigated their opinions about the question of whether cognitive decline in patients with chronic kidney disease may affect their eligibility for kidney transplantation.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Our results show that most clinicians working with patients affected by chronic kidney disease think that cognitive decline may challenge their eligibility for transplantation despite data that suggest that, in some patients, cognitive problems improve after kidney transplantation.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>We conclude that three needs emerge as particularly pressing: defining agreed-on standards for a multifaceted and multifactorial assessment (i.e. including both clinical/medical and psychosocial factors) of candidates with chronic kidney disease to kidney transplantation; further investigating empirically the causal connection between chronic kidney disease and cognition; and further investigating empirically the possible partial reversibility of cognitive decline after kidney transplantation.</jats:p> </jats:sec>
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Funding kidney research as a public health priority: challenges and opportunities
(Oxford University Press (OUP), 2021-12-31)
Zoccali, Carmine
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Vanholder, Raymond
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Wagner, Carsten A
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Anders, Hans-Joachim
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Blankestijn, Peter J
Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies.
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Present and future of CONNECT: a new and compelling project of modern medicine
(Oxford University Press (OUP), 2021-12-28)
Capasso, Giovambattista
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Wanner, Christoph
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Brain dysfunction in tubular and tubulointerstitial kidney diseases
(Oxford University Press (OUP), 2021-12-28)
Viggiano, Davide
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Bruchfeld, Annette
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Carriazo, Sol
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de Donato, Antonio
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Endlich, Nicole
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.
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Mild cognitive impairment and kidney disease: clinical aspects
(Oxford University Press, 2019-04-09)
Viggiano, Davide
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Wagner, Carsten A
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Blankestijn, Peter J
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Bruchfeld, Annette
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Fliser, Danilo
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Lancet Countdown paper: what does it mean for nephrology?
(Oxford University Press, 2019)
Blankestijn, Peter J
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Bruchfeld, Annette
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Capasso, Giovambattista
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Fliser, Danilo
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Fouque, Denis
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Children of a lesser god: exclusion of chronic kidney disease patients from clinical trials
(Oxford University Press, 2019)
Zoccali, Carmine
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Blankestijn, Peter J
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Bruchfeld, Annette
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Capasso, Giovambattista
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Fliser, Danilo
The exclusion of chronic kidney disease (CKD) patients from clinical trials-particularly cardiovascular trials-remains a long-standing, unsolved problem, which prevents the optimization of clinical care in these patients. The situation recalls the insufficient recruitment of women in cardiovascular trials until the 1980s, a problem that was only resolved following regulatory interventions. Regulatory agencies are in a unique position to promote recruitment of CKD patients in clinical trials. The main stakeholders, namely patients' associations and scientific societies, should make major lobbying efforts to persuade these agencies that the issue is an absolute public health priority.
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Nephrology and Public Policy Committee propositions to stimulate research collaboration in adults and children in Europe
(Oxford University Press, 2019-09-01)
Massy, Ziad A
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Caskey, Fergus J
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Finne, Patrik
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Harambat, Jerome
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Jager, Kitty J

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