MOMENTUM

Chronic kidney disease (CKD) is a global healthy priority, affecting 850 million people worldwide, with up to 60% having cognitive impairment. Mild Cognitive Impairment in CKD (MCI-CKD), despite its high risk of progression to dementia, is under-recognised, under-researched and poorly managed. The underlying mechanisms and key players of MCI-CKD remain poorly understood, hindering early diagnosis and effective interventions. The multidisciplinary MOMENTUM project will integrate clinical, mechanistic and patient-centred perspectives to address these unmet needs by elucidating the pathophysiology of MCI-CKD – with special focus on Uremic Toxins (UTs) – and by identifying reliable biomarkers of MCI-CKD diagnosis and progression. MOMENTUM aims to: (i) investigate the association between circulating UT levels, cognitive impairment and brain alterations in MCI-CKD through a multicentre cross-sectional and longitudinal study; (ii) assess blood-brain barrier (BBB) integrity in vitro and ex vivo, linking UT activity and BBB injury with cerebral dysfunction; (iii) establish causal links between UT exposure, brain injury and neurocognitive outcomes in zebrafish and murine CKD models, by mechanistic analyses not feasible in humans; (iv) investigate the role of the gut microbiome in BBB disruption and cognitive decline; (v) address ethical, legal and social issues, and foster active engagement of patients living with MCI-CKD, clinicians and other stakeholders. MOMENTUM will allow the first comprehensive characterisation of MCI-CKD, generating actionable knowledge for improved clinical outcomes. It will enable and inform improvements of patients’ clinical management, aligning with EU priorities to improve sustainability and quality of healthcare. MOMENTUM will ultimately yield new opportunities for MCI-CKD early diagnosis and targeted interventions, with substantial benefits for patients, caregivers and health systems.