Dialysis Unplugged: Calciphylaxis Part I

Professor Hans Selye
His seminal book: 'Calciphylaxis" in 1962
set the stage for what we know today

About 10 days ago I completed my 2 week dialysis attending stint at the Brigham. As I reflect about how things have changed since my first stint as a nephrology attending many years ago at Tufts-New England Medical Center, the one thing that seems very different is the relatively high prevalence of calciphylaxis.

There is no question that we had a pretty sick dialysis population 25 years ago when I started nephrology at Tufts. But what I don't remember seeing much of, as far I remember, is calciphylaxis. This condition has been around for a generation but was rare. In fact, the best work originates from landmark studies performed by Hans Selye from Montreal.  The literature cites a prevalence rate of 1% but the numbers are imprecise, and to me, it seems more frequent than that.

On the dialysis service at the Brigham and Women’s this past December I saw 3 patients over a period of 2 weeks with calciphylaxis.

One of the patient’s was a woman in her eighties that I had cared for the past 10 years. She had presented with lower extremity ulcers – eschars like the ones in the picture – that had been worked up and a biopsy had been done that showed typical findings of calciphylaxis. She told me that the ulcers hurt and that she had heard from other doctors that these ulcers were a bad sign – "like developing a cancer".

In October 2011, a very nice review was published in the American Journal of Nephrology by Dr. Edward Ross from Gainesville, Florida. It’s available open access here and is definitely one of the best reviews out there. The clinical aspects of calciphylaxis were discussed here.

The most telling sentence in Ross’s review is the following: Calciphylaxis [calcific uremic arteriolopathy (CUA)] is a well-described but poorly understood disorder of high morbidity and mortality (60–80%) that has limited therapeutic options.

Calciphylaxis is easy to treat because we really don’t know whether what we are doing makes a difference.

Ross lists key interventions that we also use in our patients:

Eschar in a patient with calciphylaxis (source: trip database)

1. Treat or prevent hypercalcemia and avoid a positive calcium balance:

• discontinue calcium-based phosphate binders
• adjust hemodialysis or peritoneal dialysis dialysate by avoiding ‘high’ and using  ‘low’ calcium concentrations (e.g. 2 or even 1.5 mEq/L hemodialysate calcium)
• discontinue or minimize use of vitamin D analogs

2. For hyperparathyroidism, consider emergent parathyroidectomy for severe disease, or aggressive medical control with calcimimetics (e.g. cinacalcet).

3. Aggressive control of hyperphosphatemia with noncalcium-based binders (e.g. sevelamer HCl or carbonate, lanthanum carbonate) and dietary phosphate restriction.

4. Avoid (or relocate) subcutaneous injections, skin trauma and unnecessary skin biopsies or instrumentation.

5. Discontinue warfarin and use alternative anticoagulants as needed.

6. Evaluate for primary hypercoagulability and anticoagulate as indicated. Look for including proteins C and S and vitamin K deficiencies, antiphospholipid syndrome, and AT3 deficiency. Avoid procoagulant medications and supratherapeutic calcineurin inhibitor levels.

7. Meticulous wound care, using specialized nursing care (e.g. ICU or burn ICU as appropriate). Surgical debridement  of nonviable tissue.

8. General supportive measures including aggressive pain control.

9. Consider intravenous sodium thiosulfate therapy (STS).  The use of STS was initially based on the notion that STS complexes with calcium and thereby increases the solubility of calcific deposits, thereby enhancing their hemodialysis clearance. Lately, the antioxidant (via enhanced glutathione generation) role of STS has been emphasized.

At the Brigham we are using STS in virtually all of our patients with biopsy proven STS. Whether it works or not is anybody’s guess. (In Calciphylaxis Part II there will be a more detailed discussion of STS).