Hemodialysis Patients Have Impaired Cerebrovascular Reactivity to CO2 Compared to Chronic Kidney Disease Patients and Healthy Controls: A Pilot Study

Abstract

Introduction: Recurrent hemodialysis (HD)-induced ischemia has emerged as a mechanism responsible for cognitive impairment in HD patients. Impairment of cerebrovascular function in HD patients may render the brain vulnerable to HD-induced ischemic injury. Cerebrovascular reactivity to CO 2 (CVR) is a noninvasive marker of cerebrovascular function. Whether CVR is impaired in HD patients is unknown. In this study, we compared CVR between healthy participants, HD patients, and chronic kidney disease (CKD)patients not yet requiring dialysis.Methods: This was a single-center prospective observational study carried out at Kidney Clinical Research Unit in London, Canada. We used carefully controlled hypercapnia to interrogate brain vasomotor control. Transcranial Doppler was combined with 10-mm Hg step changes in CO 2 from baseline to hypercapnia (intervention) and back to baseline (recovery) to assess CVR in 8 HD, 10 CKD, and 17 heathy participants.Results: HD patients had lower CVR than CKD or healthy participants during both intervention and recovery (P < 0.0001). There were no differences in CVR between healthy and CKD participants during either intervention (P ¼ 0.88) or recovery (P ¼ 0.99). The impaired CVR in HD patients was independent of CO 2induced changes in blood pressure, heart rate, cardiac output, or dialysis vintage. In the CKD group, CVR was not associated with the estimated glomerular filtration rate.Conclusions: Our study shows that HD patients have impaired CVR relative to CKD and healthy participants. This renders HD patients vulnerable to ischemic injury during circulatory stress of dialysis and may contribute to the pathogenesis of cognitive impairment.

Cerebrovascular pulsatility index is higher in chronic kidney disease

“…In contrast, in a recent study in a mouse model of CKD (DB1/2J mice with uremic vascular calcification), cerebrovascular reactivity to hypercapnia did not differ as compared to wild‐type mice, although the increase in blood flow was more rapid and decreased prematurely (Choi et al, 2021 ). This is consistent with a recent pilot study that reported impaired cerebrovascular reactivity to hypercapnia in chronic dialysis patients but not patients with non‐dialysis dependent stage 4–5 CKD, as compared to healthy controls (Slessarev et al, 2021 ). Cerebrovascular reactivity has been widely used as an index of cerebrovascular function and health, and predicts adverse clinical outcomes such as stroke, dementia, and mortality (Markus & Cullinane, 2001 ; Portegies et al, 2014 ; Wolters et al, 2016 ).…”

Cerebral blood flow pulsatility and cerebral artery stiffness acutely decrease during hemodialysis

“…Furthermore, neither PCO 2 nor bicarbonate concentration were significantly associated with either baseline mean MCAv or changes in MCAv during hemodialysis. This lack of association between PCO 2 and MCAv might suggest a reduction in CVRCO 2 during hemodialysis, a finding in line with recent pilot work (Slessarev et al, 2021 ). Indeed, Slessarev et al observed a reduction in CVRCO 2 in hemodialysis patients, when compared to CKD and healthy control participants.…”

The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis

“…Together, these factors impair the cerebral vasoregulatory response that is needed in both CVR and cerebral autoregulation, leading to decreases in CBF and associated hypoperfusion. Preliminary studies show that both CVR and cerebral autoregulation may be impaired in patients on HD 11 , 13 . Our model relating lower CVR with greater decline in ScO 2 during HD improved when accounting for the change in systemic BP during HD, suggesting it is the vasoregulatory response that is common to both CVR and cerebral autoregulation that is impaired.…”

“…CVR in Patients on HD CVR has been studied in a small cohort of patients on HD with some variability in results. 13,28,[36][37][38] The differences between studies may be due to the different modalities of measuring CBF, the type of CO 2 stimulus, and the age of the patient group. Using positron emission tomography, Kuwabara et al 38 found a decreased CVR in response to 5% CO 2 inspiration in patients on HD and that the CVR was related to baseline CBF and hematocrit levels.…”

“…37 These characteristics are different from the general characteristics of the HD population in the United States. In a small but more age-relevant cohort, Slessarev et al 13 found that patients on HD have an impaired CVR when compared with both healthy controls and patients with predialysis CKD. Thus, in patients on HD more similar in age and comorbidity to our study participants, impaired CVR is more common and is likely a relevant risk factor for cerebral hypoperfusion.…”