Hemodialysis-Related Acute Brain Injury Demonstrated by Application of Intradialytic Magnetic Resonance Imaging and Spectroscopy

Abstract

Significance Statement Hemodialysis (HD) results in reduced brain blood flow, and HD-related circulatory stress and regional ischemia are associated with brain injury over time. However, studies to date have not provided definitive direct evidence of acute brain injury during a HD treatment session. Using intradialytic magnetic resonance imaging (MRI) and spectroscopy to examine HD‐associated changes in brain structure and neurochemistry, the authors found that multiple white (WM) tracts had diffusion imaging changes characteristic of cytotoxic edema, a consequence of ischemic insult and a precursor to fixed structural WM injury. Spectroscopy showed decreases in prefrontal N-acetyl aspartate (NAA) and choline concentrations consistent with energy deficit and perfusion anomaly. This suggests that one HD session can cause brain injury and that studies of interventions that mitigate this treatment's effects on the brain are warranted. Background Hemodialysis (HD) treatment-related hemodynamic stress results in recurrent ischemic injury to organs such as the heart and brain. Short-term reduction in brain blood flow and long-term white matter changes have been reported, but the basis of HD-induced brain injury is neither well-recognized nor understood, although progressive cognitive impairment is common. Methods We used neurocognitive assessments, intradialytic anatomical magnetic resonance imaging, diffusion tensor imaging, and proton magnetic resonance spectroscopy to examine the nature of acute HD-associated brain injury and associated changes in brain structure and neurochemistry relevant to ischemia. Data acquired before HD and during the last 60 minutes of HD (during maximal circulatory stress) were analyzed to assess the acute effects of HD on the brain. Results We studied 17 patients (mean age 63±13 years; 58.8% were male, 76.5% were White, 17.6% were Black, and 5.9% were of Indigenous ethnicity). We found intradialytic changes, including the development of multiple regions of white matter exhibiting increased fractional anisotropy with associated decreases in mean diffusivity and radial diffusivity—characteristic features of cytotoxic edema (with increase in global brain volumes). We also observed decreases in proton magnetic resonance spectroscopy–measured N-acetyl aspartate and choline concentrations during HD, indicative of regional ischemia. Conclusions This study demonstrates for the first time that significant intradialytic changes in brain tissue volume, diffusion metrics, and brain metabolite concentrations consistent with ischemic injury occur in a single dialysis session. These findings raise the possibility that HD might have long-term neurological consequences. Further study is needed to establish an association between intradialytic magnetic resonance imaging findings of brain injury and cognitive impairment and to understand the chronic effects of HD-induced brain injury. Clinical Trials Information: NCT03342183.

Assisted peritoneal dialysis: Position paper for the ISPD

“…There is evidence of a higher prevalence of cognitive decline in the HD population compared to the general population with the potentially rapid decline associated with drops in cerebral blood flow and evidence of acute brain injury during HD sessions. [11][12][13][14] People with cognitive decline may be more tolerant of receiving dialysis in a familiar home setting rather than a busy and often noisy HD centre but will require assistance to do so.…”

Update on Hemodialysis-Induced Multiorgan Ischemia

“…This is indicative of new cytotoxic and some secondary vasoactive edema. 99 allows the extravasation of harmful plasma constituents into brain tissue and sets up a variety of potentially damaging pathophysiologic processes. Initial pilot data suggest that the blood-brain barrier is indeed damaged in patients requiring hemodialysis as compared with individuals with normal kidney function.…”

“…Acutely, hemodialysis results in significant reduction in choroid plexus perfusion pressure and an acute intradialytic reduction in CSF volume. 99 This results in an increase in the effective weight of the brain (reduced normally to approximately 50 g as it floats in CSF), combined with an increase in brain volume (due to acute edema) and downward pressure of the brain into the base of the skull. These effects may be of clinical importance in generating dialysis-induced headache and postdialytic fog with reduced mentation.…”

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“…Cardiovascular events are a leading cause of morbidity and mortality in patients receiving RRT [4], and intradialytic hypotension is common and appears to contribute to decreasing organ perfusion [5,6] and sympathetic stress [7][8][9]. At the same time, fluid removal is necessary during dialysis and likely to lead to a degree of intravascular volume depletion, which can be expected to decrease cardiac output (CO).…”