Study to Evaluate the Effects of AV-001 on HD-induced Brain Injury.

Cognitive decline is increasingly recognized among patients receiving maintenance hemodialysis (HD). This can include trouble remembering, slower thinking or mentally feeling foggy. This research is being done to determine if a new medication (AV-001) can protect the brain from injury caused by hemodialysis by strengthening blood vessels in the brain and reducing inflammation. If successful, this research could lead to better protection for the brains of people undergoing regular dialysis, potentially reducing the risk of cognitive decline and stroke.

Hemodialysis provides life-sustaining treatment for many chronic kidney disease patients around the world. Moderate to severe cognitive impairment is very common in HD patients with up to 70% being affected who are ≥ 55 years of age and \~ 10% in those between 21-39 years of age. Significant cognitive impairment is evident within 6 months of starting HD. This study is a phase 2 exploratory study in patients receiving hemodialysis treatments. Investigators will recruit 60 patients from the renal program at the London Health Sciences Centre. Study participants will receive AV-001 (low or high dose) or placebo 60 minutes prior to HD initiation at 3 HD treatment sessions within 1 week (Monday, Wednesday and Friday) Study participants will also undergo: * Vital sign collection (blood pressure and heart rate) * Blood collection * Cognitive assessments * Vascular ultrasound * MRI

Inclusion Criteria: * Ability to provide informed consent * Male and non-pregnant female patients (\>18 years old) * HD for ≥ 3 months * Thrice weekly HD schedule Exclusion Criteria: * HD \<90 days * Contraindication to MRI * Established severe cognitive impairment (Montreal Cognitive Assessment test (MoCA) \<18 or formal diagnosis of dementia) * Previous clinical stroke * Pregnancy, breastfeeding, or intending pregnancy * Intradialytic hypotension event (defined as: drop in SBP ≥40mmHg + symptoms + intervention) in previous month as evidenced by HD record