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Background Cerebral blood flow (CBF) may decrease during intermittent hemodialysis (IHD). Patients with acute kidney injury (AKI) may be more vulnerable to cerebral hypoperfusion than patients with end-stage renal disease (ESRD), due to concomitant critical illness and hemodynamic instability. Methods In this observational, prospective study, we measured mean flow velocity at the level of the middle cerebral artery by transcranial Doppler at the start, after 2 h and at the end of a hemodialysis session in 15 consecutive patients with AKI and critical illness referred to the nephrological intensive care unit of a university hospital and in 12 patients with ESRD on regular treatment thrice weekly, who served as controls. We compared end-dialysis changes from baseline in mean flow velocity between the study groups and examined the correlation between this change and that of other relevant clinical parameters. Results Mean flow velocity decreased significantly at end-dialysis in the patients with AKI, but not in those with ESRD (P = 0.02). This difference persisted after adjusting for baseline mean flow velocity and net ultrafiltration volume. No significant correlations were found in either group between changes in mean flow velocity and changes in mean blood pressure (AKI: r = −0.27, P = 0.34; ESRD: r = 0.15, P = 0.68), SUN (AKI: r = −0.33, P = 0.25; ESRD: r = 0.06, P = 0.85), plasma HCO3− (AKI: r = −0.52, P = 0.24; ESRD: r = −0.18, P = 0.59), hematocrit (AKI: r = 0.08, P = 0.71; ESRD: r = −0.19, P = 0.65) or arterial oxygen content (AKI: r = −0.17, P = 0.36; ESRD: r = −0.33, P = 0.43). Conclusions Our data suggest that AKI patients may be more vulnerable than ESRD patients to cerebral hypoperfusion during IHD. Our findings do not support a clear-cut role of rapid changes in blood osmolarity, rheological properties or vasoreactivity of the cerebral circulation to O2 supply in modulating CBF during hemodialysis. [ABSTRACT FROM PUBLISHER]