A few months ago, we posted about an acid-base primer that was being offered free for fellows in the US.

During the 5-day period from Wednesday, August 23 - Sunday, August 27, you can get a free copy of this ebook (kindle) edition of The Painless Guide to Mastering Clinical Acid-Base. Simply go to Amazon, search the title of Amazon ID number (B06XRM56TY), or click here, and you will find the ebook priced at $0.00 during those 5 days. Once you "purchase" the book, it will remain permanently in your Amazon library and you will be able to load it onto any device that has a Kindle app linked to your account. Feel free to notify students, residents, nurses or any others who might benefit. There is no limit to the number of persons who can get the download.

Posted by Ben Abelow

August Wash U Nephrology Web Episode now available

The monthly nephrology webisode from Wash U is posted and available for your viewing pleasure!  For August, we went on the road and recorded with some special guests from Rush University Medical Center in Chicago.  Try your hand at unraveling this tricky CPC with some complicated histology:

"32 year old African American male with uncontrolled hypertension, HIV, and a positive RPR presents with AKI and shortness of breath."

Midwest Point of Care Ultrasound Workshop

Washington University School of Medicine 

Point of Care Ultrasound Workshop  

Sunday, September 10, 2017

 Institute of Public Health

600 S.Taylor Ave.

Dear Friends. 

Point of care ultrasound has emerged as a powerful tool to assess volume status. This workshop will be part of the Midwest Nephrology + Transplant Symposium.  In this workshop we will review the fundamentals of beside US including heart, lung, and IVC assessment along with US-guided line placement and solid organ biopsy (kidney). 

For more info.

Panda Eyes

I recently saw an elderly woman in clinic. She had a background history of migraine headaches and had been investigated over the past 18 months for recurrent syncopal episodes. She had at least 5 episodes that began with palpitations usually on minimal exertion. Apart from these episodes, she was fit and active. Her ECHO showed only mild LV hypertrophy and mild pulmonary hypertension. EKGs were unrevealing.

Two years ago she had been seen by a dermatologist for sun-related skin lesions and had mentioned that she had recurrent bruising around her eyelids. She had taken a photo of these lesions and they were noted to be purpuric. They would come and go and usually last for a couple of months when they were there.

She was referred to my clinic for investigation of mild albuminuria. She had ~500mg albumin for approximately 5 years with no significant change. Her renal function had always been otherwise normal apart from one single increase in creatinine was unexplained and returned to normal in a few days. She had no significant risk factors for kidney disease apart from long term NSAID use for her migraines.

As part of her investigations, she had an SPEP and free light chains. The results showed that she has an IgG lambda paraprotein likely related to an underlying multiple myeloma. Re-review of her ECHO images showed that they were consistent with infiltrative disease and she is currently undergoing work-up for AL-amyloidosis.

Periorbital purpura is a rare finding in patients with amyloidosis occurring in about 15% of patients. It is thought to be a result of Factor X deficiency due to binding of Factor X by the amyloid fibrils. It is generally atraumatic and tends to recur without treatment of the underlying amyloid. It is almost pathognomic of amyloid and its presence should prompt testing for AL amyloid.

Image from NEJM

Dialysis for dementia?

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%.

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.

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.

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.

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. 

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.

Post by Dearbhla Kelly