cerebrovascular reactivity in adults on hemodialysis and association with intradialytic cerebral hypoperfusion

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ABSTRACT The hemodialysis (HD) population carries a substantial burden of cognitive impairment and ischemic brain pathology, especially small vessel ischemic disease with white matter disease, lacunae, and atrophy. Risk of cognitive impairment in HD patients is twice that of peritoneal dialysis patients, suggesting the HD process itself may contribute to ischemic brain pathologies and the associated cognitive impairment. Conventional HD is associated with myocardial dysfunction and intravascular fluid shifts, which can lead to significant decline in blood pressure (BP) during the HD session. To maintain cerebral perfusion during decline in systemic BP the downstream cerebral microvasculature must vasodilate, a physiological response that occurs as part of cerebral autoregulation (CA). The same vasodilation occurs in response to chemo stimuli (i.e. pCO2) using cerebrovascular reactivity (CVR) mechanisms. In the HD population, increased arteriosclerosis, diabetes, hypertension, inflammation, and vascular calcification may combine to impair these cerebral blood flow regulatory mechanisms and lead to increased risk of cerebral hypoperfusion and ischemia during HD-induced decline in BP. Through this R03 proposal we will investigate cerebral blood flow regulation during HD by measuring CVR in an HD cohort and determining if impaired CVR is associated with greater risk of decline in cerebral perfusion during HD. We focus on CVR as it can be measured safely and non-invasively in older patients with vasculopathy—compared to inducing hypotension to measure CA—and can be done prior to dialysis initiation. In Aim 1, we measure CVR in an HD cohort and identify risk factors, including renal disease specific factors, for lower CVR. We will measure CVR with breath-hold induced hypercapnia and quantify the change in blood flow velocity through cerebral vessels using transcranial Doppler. In Aim 2, we will measure the association between CVR and change in cerebral perfusion during HD, to determine if CVR can be used to identify patients who are at greatest risk for cerebral ischemic disease on HD. This will provide important clinical knowledge needed to optimize dialysis therapy to avoid cerebral ischemic injury. Finally, in Aim 3 we will explore the relationship between CVR and CA—distinct mechanisms that control cerebral blood low—to see if small vessel cerebral vascular disease may be a common underlying pathology to both mechanisms in HD patients. This proposal will improve our understanding of cerebral blood flow regulation in HD patients, and determine if CVR can be used to identify patients at risk for cerebral ischemic injury during HD. The results will inform the design of an R01 evaluating CVR changes over time in pre-dialysis kidney disease patients and comparing to those on conventional HD and other dialysis modalities (peritoneal dialysis or nocturnal HD) that avoid rapid BP changes. This information could be used in dialysis decision-making to guide our high-risk patients to dialytic therapy that is concordant with preserving cognitive capacity.