Cerebrovascular pulsatility index is higher in chronic kidney disease

Abstract

Patients with chronic kidney disease (CKD) are more likely to die of cardiovascular diseases, including cerebrovascular disease, than to progress to end‐stage kidney disease. Cerebrovascular dysfunction, characterized by reduced cerebrovascular reactivity, cerebral hypoperfusion, and increased pulsatile flow within the brain, precedes the onset of dementia and is linked to cognitive dysfunction. However, whether impaired cerebrovascular function is present in non‐dialysis dependent CKD is largely unknown. Using transcranial Doppler, we compared middle cerebral artery (MCA) blood velocity response to hypercapnia (normalized for blood pressure and end‐tidal CO2; a measure of cerebrovascular reactivity) and MCA pulsatility index (PI; a measure of cerebrovascular stiffness) in patients with stage 3–4 CKD vs. age‐matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function), measured carotid‐femoral pulse‐wave velocity (PWV; aortic stiffness), and assessed ex vivo nitric oxide (NO) and reactive oxygen species (ROS) production from human brain endothelial cells incubated with serum obtained from study participants. MCA PI was higher in patients with CKD vs. controls; however, normalized MCA blood velocity response to hypercapnia did not differ between groups. Similar results were observed in a validation cohort of midlife and older adults divided by the median estimated glomerular filtration rate (eGFR). MCA PI was associated with greater large‐elastic artery stiffness (carotid‐femoral PWV), worse executive function (trails B time), lower eGFR, and higher ex vivo ROS production. These data suggest that impaired kidney function is associated with greater cerebrovascular stiffness, which may contribute to the known increased risk for cognitive impairment in patients with CKD.

Cerebrovascular Pulsatility Index Is Reduced in Autosomal Dominant Polycystic Kidney Disease

“…All vascular measurements followed standard recommendations, including an overnight fast [15]. Transcranial Doppler (Lucid M1 System, NovaSignal, Los Angeles, CA, USA) was used to assess CVR, by measuring ΔMV MCA in response to a vasodilatory hypercapnic challenge (i.e., via CO 2 breathing), as described previously [16, 17]. A 2-MHz transcranial Doppler ultrasound probe was positioned at the temporal window on the right side of the body and held in place by an adjustable headband to continuously assess MCA blood velocity (MCAv).…”

“…The Gosling PI was used to calculate pulsatile cerebrovascular velocity (PI = MCAv [systolic] − MCAv [diastolic]/ MV MCA ), as described previously [17, 19]. PI positively associates with arterial stiffness [10]; a higher value reflects an impaired ability of the cerebral arteries to buffer a large increase in pressure delivered via the carotid arteries from the heart to the brain.…”

“…ICA and VA diameter were measured during the diastolic phase of the cardiac cycle and averaged over a 30 s period. CBF was calculated as CBF = mean blood velocity × π (diameter/2) 2 for each artery, as described previously [17, 20]. The sum of CBF calculated for the right ICA and VA was multiplied by two for a bilateral estimate of total CBF [20].…”

Cerebrovascular Function is Altered in Hemodialysis Patients

“…14 Impaired CVR may be most prominent in dialysis patients as a study comparing patients with CKD (eGFR of 39613 ml/min per 1.73 m 2 ) and healthy controls did not find a difference in CVR between the groups, although the patients with CKD had greater cerebral arterial stiffness. 37 It may be that patients requiring dialysis have even greater arterial stiffness leading to worse CVR. The patient population and characteristics are also important to consider.…”

“…In our study, we found significant difference in the percent of impaired CVR voxels between hemodialysis patients and controls but did not note differences when looking at the whole brain averaged CVR. In the previous study, they used transcranial Doppler to measure change in middle cerebral artery velocity in response to hypercapnia to measure CVR, 37 which looks more globally at small vessel reactivity compared with the individual voxel changes that we measured with the BOLD MRI. If impaired CVR occurs more regionally, differences may be washed out when looking at whole brain averages but are detected when looking at the number of affected individual voxels or specific regions.…”