Cerebrovascular function is not altered in patients with stage 3 and 4 chronic kidney disease
Authors: Skow Rachel , Grotle Ann-Katrin , Kaur Jasdeep , Young Benjamin , Nandadeva Damsara , Stephens Brandi , Mohan Ponnaiah , Fadel Paul 
Published: May 2023

Background: Chronic kidney disease (CKD) affects more than 37 million US adults and is associated with a 3-5-fold increased risk of stroke. An attenuated cerebrovascular function may contribute to an increased risk of stroke in patients with CKD. However, our understanding of cerebrovascular function in CKD has mainly been limited to patients with end-stage renal disease or those who have already suffered from stroke. Therefore, the purpose of this study was to test the hypothesis that patients with CKD (stage 3-4) without a history of stroke would exhibit impaired cerebrovascular function compared to healthy, aged-matched adults. Methods: We studied 7 patients with stage 3-4 CKD (65 ± 10 yrs, 4 females; eGFR 39 ± 11 ml/min/1.73m2) and 7 healthy controls (58 ± 7 yrs, 5 females). Beat-to-beat blood pressure (Finapres), partial pressure of end-tidal carbon dioxide (PETCO2; capnography), and middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound) were measured continuously during six-minutes of quiet rest and a hypercapnic rebreathing protocol that increased PETCO2 up to +15mmHg. Spontaneous dynamic cerebral autoregulation (dCA) was determined using transfer function analysis in the low frequency range (0.07-0.20Hz) for phase, gain, and coherence. Cerebrovascular reactivity to CO2 was determined as ΔMCAv and cerebrovascular conductance index (CVCi; mean MCAv/mean arterial blood pressure [MAP]) in response to increasing PETCO2 levels (Δ 3, 6, 9, 12, and 15 mmHg) and as the slope of the linear relationship between ΔMCAv or ΔCVCi and ΔPETCO2. Results: Resting MAP was not different between groups (p=0.108). Likewise, mean MCAv at rest was also not different between groups (control: 66 ± 11 cm/s; CKD: 57 ± 10 cm/s; p=0.121), however, CVCi was lower in patients with CKD (p=0.045). There were no differences between groups for low frequency gain (control: 0.95 ± 0.24 cm/s/mmHg; CKD: 0.87 ± 0.32cm/s/mmHg; p=0.642). Low frequency phase and coherence were also not different between groups (p=0.572 and 0.214, respectively). During the CO2 rebreathe, MCAv and CVCi increased in both groups (main effect of PETCO2: p<0.001). However, ΔMCAv and ΔCVCi were not different between controls and patients with CKD (interaction effect: p=0.760 and p=0.656, respectively). MCAv and CVCi reactivity slopes were also not different between groups (e.g., MCAv slope; control: 4.1 ± 1.7 cm/s/mmHg; CKD: 5.0 ± 1.0 cm/s/mmHg; p=0.247). Conclusion: In contrast to our hypothesis, these preliminary results suggest that patients with stage 3-4 CKD do not exhibit impaired cerebrovascular function when compared to healthy age-matched controls. This project was supported by the National Heart, Lung, and Blood Institute R01 HL-127071. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.