Effect of Dialysis on Cerebral Blood Flow and Cognition

Hemodialysis and the Brain

Cognitive impairment is common in patients with end-stage renal disease treated with hemodialysis. Despite this well-recognized link, the etiology of cognitive impairment in hemodialysis patients has remained elusive. This has led to significant challenges in finding therapies to prevent or potentially reverse cognitive impairment.

A new important study published in the Journal of the American Society of Nephrology sheds new light on potential contributors to cognitive impairment by studying cerebral blood flow.^[1] In this study of 12 older hemodialysis patients (aged ≥65 years) treated with hemodialysis in The Netherlands, the investigators studied the acute effect of hemodialysis on cerebral blood flow, measured by gold-standard [¹⁵O]H₂O PET-CT.

PET-CT was performed at three time points: prior to dialysis start, shortly after the start of dialysis (mean time, 39 minutes from start of dialysis; range, 28-61 minutes), and at the end of dialysis (mean time, 209 minutes from the start of dialysis; range, 168-223 minutes). Mean ultrafiltration volume was 1.9 L, ultrafiltration rate was 6.7 ml/hr/kg, and mean weight change was -1.6 kg. The mean change in systolic blood pressure over the dialysis treatment was a decline of 9 mm Hg (range, -27 to 10 mm Hg), and change in mean diastolic blood pressure was a decline of 5 mm Hg (range, -14 to 4 mm Hg). The lowest individual nadir in any individual participant was 105 mm Hg.

In the study, on average, global cerebral perfusion rate declined from a baseline of 34.5 mL/100 g/min to 30.5 mL/100 g/min at the end of dialysis. The relative change in crude cerebral blood flow from the start to end of dialysis was, on average, -10% (standard deviation [SD], 15%) for global perfusion; -11% (SD, 17%) for frontal perfusion, -11% (SD, 16%) for parietal perfusion, -10% (SD, 14%) for temporal perfusion, -9% (SD, 13%) for occipital perfusion, -10% (SD, 13%) for cerebellum perfusion, and -10% (SD, 16%) for thalamus perfusion. Thus, cerebral blood flow declined in all volumes of interest.

There was one participant in the study who was symptomatic (who lost consciousness) and had a decline of cerebral blood flow of 20%. Of hemodialysis treatment-related factors, a higher ultrafiltration volume, a higher tympanic temperature, and a lower partial pressure of carbon dioxide were associated with a lower cerebral blood flow in almost all regions. Of note, blood pressure or mean arterial pressure were not associated with lower cerebral blood flow.

The findings of this study are certainly intriguing. The significance of a 10% decline in cerebral blood flow remains unknown. Other literature has defined the absolute threshold for cerebral ischemia as <10 mL/100 g/min and <20 mL/100 g/min for the area surrounding the ischemic area. In this study, the lowest cerebral blood flow was 24.4 mL/100 g/min. However, it is not known whether these same thresholds apply to dialysis patients who may be more "vulnerable" to small changes in cerebral blood flow given the repetitive injury associated with dialysis several times a week. It is also unclear whether repeat episodes of decline in cerebral blood flow during dialysis lead to subsequent ischemic brain lesions or cognitive decline.

Dialysis-Induced Cerebral Ischemia

While this recent study was the first to rigorously study cerebral blood flow in dialysis patients, prior studies have examined other measures to define dialysis-induced cerebral ischemia. A complementary study published in 2017, also in the Journal of the American Society of Nephrology, noninvasively quantified cerebral tissue oxygenation using near-infrared spectroscopy technology among 58 hemodialysis patients over a total of 635 hemodialysis sessions.^[2] Overall, they found that cerebral ischemia (which they defined as >15% drop in cerebral oxygenation) occurred in 23.5% of hemodialysis sessions, and 32% of these episodes were symptomatic with complaints of cramping, nausea, and dizziness. Hypotensive episodes were common, with mean arterial pressures dropping by a median of 22 mm Hg and dropping below 60 mm Hg in 24% of hemodialysis sessions.

In an exploratory analysis, the authors of this paper examined the association of mean arterial pressure thresholds and cerebral ischemia. For every 10-mm Hg drop in mean arterial pressure, there was a 3% increased risk for incident cerebral ischemia (P<.001). However, when they examined the sensitivity and specificity of various blood pressure thresholds, there was no clear "safe" mean arterial pressure. For example, a mean arterial pressure threshold of 60 mm Hg had >90% specificity but <30% sensitivity. Among the study population, 47 participants were available for follow-up cognitive testing. In multivariable models, the only significant predictor of change in cognitive function was intradialytic cerebral ischemia (and not intradialytic hypotension).

Together, while these two studies are relatively small in size, both suggest that intradialytic cerebral ischemia is common. Of note, both studies did not find a strong link between blood pressure (or intradialytic changes in blood pressure) and cerebral ischemia.

Future Research Opportunities

There are several opportunities for additional studies in this important area. One, given the lack of relationship between blood pressure and cerebral ischemia, a better understanding of other dialysis treatment-related risk factors is needed. Second, while these studies utilized novel technologies, pragmatic bedside technologies that are able to assess longitudinal changes in a dialysis patient's cerebral function would be invaluable to guide clinical care. Third, comparative data on rates of cerebral ischemia with home or more frequent dialysis therapies would also be interesting and clinically useful. And, finally, once contributing factors for cerebral ischemia are identified, studies that test strategies to prevent cerebral ischemia in this patient population are needed.

While many current interventions focus on mortality as an outcome in studies of patients on dialysis, loss of cognitive function is perhaps one of the most feared patient complications and thus warrants further study to follow the lead of these two important papers.

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