When I first began learning about
Nephrology, I came across ‘dialysis
dementia’, a progressive and fatal condition described in hemodialysis
patients. Several studies
in the 1970s implicated aluminium found in phosphorus binders and dialysate
water as the cause. However, owing to modern techniques of water purification
and the use of non-aluminium phosphorus binders, ‘dialysis dementia’ is now
considered a rare
adverse effect of dialysis, with a current estimated prevalence of 0.6–1.0%.
Nephrology, I came across ‘dialysis
dementia’, a progressive and fatal condition described in hemodialysis
patients. Several studies
in the 1970s implicated aluminium found in phosphorus binders and dialysate
water as the cause. However, owing to modern techniques of water purification
and the use of non-aluminium phosphorus binders, ‘dialysis dementia’ is now
considered a rare
adverse effect of dialysis, with a current estimated prevalence of 0.6–1.0%.
Nonetheless, moderate to severe cognitive
impairment may affect 30–60% of patients undergoing hemodialysis
(HD), and two-thirds of patients undergoing peritoneal dialysis
(PD). The current pathophysiology
of cognitive impairment in patients on dialysis might be mediated by
traditional risk factors, such as older age, sex, diabetes mellitus, hypertension
and cardiovascular disease; non-traditional factors, including
hyperparathyroidism, elevated FGF-23 levels,
vitamin D deficiency, anemia, malnutrition, inflammation, and oxidative stress;
and dialysis-associated factors, such as adequacy, dialysis modality, hemodynamic
instability during the procedure and solute shifts.
impairment may affect 30–60% of patients undergoing hemodialysis
(HD), and two-thirds of patients undergoing peritoneal dialysis
(PD). The current pathophysiology
of cognitive impairment in patients on dialysis might be mediated by
traditional risk factors, such as older age, sex, diabetes mellitus, hypertension
and cardiovascular disease; non-traditional factors, including
hyperparathyroidism, elevated FGF-23 levels,
vitamin D deficiency, anemia, malnutrition, inflammation, and oxidative stress;
and dialysis-associated factors, such as adequacy, dialysis modality, hemodynamic
instability during the procedure and solute shifts.
It was with interest then that I read
recent research
suggesting that peripheral clearance of amyloid-β (Aβ) by PD could help to
reduce the amyloid plaque burden in the brain, potentially representing a new
therapeutic approach for Alzheimer disease (AD). In this study, plasma Aβ levels before and
immediately after PD in patients with CKD and in APP/PS1 mice (a standard
animal model of AD) were measured. In both cases, plasma Aβ40 and Aβ42
levels were significantly reduced after dialysis. In the animal model, PD
resulted in a decrease in Aβ levels in the brain interstitial fluid with
reduced deposition even if plaque formation was well underway. The
dialysis-treated mice showed reduced levels of hyperphosphorylated tau in the
brain, suggesting a slowing of neurodegeneration along with decreased
inflammation and increased microglial phagocytosis of Aβ in the brain.
Attenuated cognitive decline was demonstrated by improved performance on the
Y-maze and open-field tests.
recent research
suggesting that peripheral clearance of amyloid-β (Aβ) by PD could help to
reduce the amyloid plaque burden in the brain, potentially representing a new
therapeutic approach for Alzheimer disease (AD). In this study, plasma Aβ levels before and
immediately after PD in patients with CKD and in APP/PS1 mice (a standard
animal model of AD) were measured. In both cases, plasma Aβ40 and Aβ42
levels were significantly reduced after dialysis. In the animal model, PD
resulted in a decrease in Aβ levels in the brain interstitial fluid with
reduced deposition even if plaque formation was well underway. The
dialysis-treated mice showed reduced levels of hyperphosphorylated tau in the
brain, suggesting a slowing of neurodegeneration along with decreased
inflammation and increased microglial phagocytosis of Aβ in the brain.
Attenuated cognitive decline was demonstrated by improved performance on the
Y-maze and open-field tests.
According to the authors, this was a
proof-of-concept study that restoration of the AD brain microenvironment and
clearance of brain Aβ could be achieved by peripheral approaches. Yet how do we
reconcile this promising experimental model with the high incidence of dementia
in our PD patients? Although the USRDS data reports the risk of incident
dementia to be lower for patients who started on PD than for those who started
on HD, it still higher than the age-matched non-dialysis cohort. The tentative
conclusion that we may draw from this is that vascular dementia is likely a far
greater contributor to cognitive impairment in this population than AD.
proof-of-concept study that restoration of the AD brain microenvironment and
clearance of brain Aβ could be achieved by peripheral approaches. Yet how do we
reconcile this promising experimental model with the high incidence of dementia
in our PD patients? Although the USRDS data reports the risk of incident
dementia to be lower for patients who started on PD than for those who started
on HD, it still higher than the age-matched non-dialysis cohort. The tentative
conclusion that we may draw from this is that vascular dementia is likely a far
greater contributor to cognitive impairment in this population than AD.
In this study PD was very potent in
removing Aβ from the blood in CKD patients. The authors highlight key differences
in the PD procedure used in this study compared to standard practice. While CKD
patients usually receive continuous ambulatory peritoneal dialysis (CAPD) or
automated peritoneal dialysis (APD) with long dwell times of 8 hours or more,
the AD mice received only 2 hours of dialysis per day. This suggests that CAPD
may be even more effective at depleting the brain Aβ burden in AD patients.
Similarly brain
Aβ deposition appears to be lower in patients who receive hemodialysis.
removing Aβ from the blood in CKD patients. The authors highlight key differences
in the PD procedure used in this study compared to standard practice. While CKD
patients usually receive continuous ambulatory peritoneal dialysis (CAPD) or
automated peritoneal dialysis (APD) with long dwell times of 8 hours or more,
the AD mice received only 2 hours of dialysis per day. This suggests that CAPD
may be even more effective at depleting the brain Aβ burden in AD patients.
Similarly brain
Aβ deposition appears to be lower in patients who receive hemodialysis.
What are the implications of this study for
us as nephrologists? Will we be dialyzing people for ‘dementia’ in the future?
Or for other neurodegenerative diseases that may benefit from peripheral
clearances such as Huntington disease or motor neuron disease? More research is definitely needed and there
will be side-effects that non-nephrologists may not appreciate but it could be
an exciting area in the future.
us as nephrologists? Will we be dialyzing people for ‘dementia’ in the future?
Or for other neurodegenerative diseases that may benefit from peripheral
clearances such as Huntington disease or motor neuron disease? More research is definitely needed and there
will be side-effects that non-nephrologists may not appreciate but it could be
an exciting area in the future.
Post by Dearbhla Kelly
