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Saturday, December 17, 2011

CONSULT ROUNDS: Calciphylaxis Treatment Options

A Pathophysiology based treatment strategy has been suggested:
1. High bone turnover/ high pth levels:- Therapy that works is cinacalcet, Vitamin D analogs, non calcium based phosphate binders, bisphosphanates, and perhaps surgical parathyroidectomy
2. high calcium phos product:- tight control with daily dialysis, avoiding calcium based binders, low Ca dialysate
3. Extracellular matrix associated soft tissue or vascular calcium deposition effects:- sodium thiosulfate enhances calcium solubility, bisphosphanates via multiple ligand pathways
4. Hypercoagulability mechanism:- avoid warfarin, change to non warfarin based agent, hyperbaric oxygen for wound healing
5. Tissue ischemia mechanism:- hyperbaric oxygen, optimize anemia, sodium thiosulfate
6. Macrophage activation:- avoid biopsies if possible.


Traditionally above treatments have always been mentioned
Bisphosphanates have now started coming into the literature to be used in this disease entity.


1. Mechanism might be calcium mediated and control of high bone absorption
2. Independent effet on bone and tissue calcification via NF-B pathways and RANKL
3. Inhibition of phosphate transport and calcium phosphate crystal formation
4. Anti inflammatory effects towards macrophages and TNF and interleukins


When to use them?
1. No clinical improvement with above mentioned common therapies
2. Failed 2 weeks of sodium thiosulfate as well
3. Usually use Pamidronate 30mg IV ( 5 doses over 48 days) or Aldentronate 35mg weekly
4. Successful treatment has been described in the literature.


Check out the original references:


http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=332221&Ausgabe=255569&ProduktNr=223979&filename=332221.pdf
http://www.ncbi.nlm.nih.gov/pubmed/18070019
http://www.ncbi.nlm.nih.gov/pubmed/18021849
http://www.ncbi.nlm.nih.gov/pubmed/15252173

2 comments:

  1. Stop coumadin, if necassary switch to heparin; stop calcium intake; and I strongly believe in biphosphonates though needs more trials; a trial with low dose steroids as antiinflammatory medication cold be possible; plan daily dialysis to decrease phosphorus and calcium load. What else do we have in hand?
    Siren Sezer
    sirensezer@hotmail.com

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  2. The article in my mind is a good comprehensive description of a systemic disorder, where a pragmatic approach in a multidisciplinary fashion should be undertaken. Caution should be exercised with the use of Vit D analogues in these patients; Vit D downregulate Fetuin protein; which helps clears vascular Ca-Phos deposits;
    Chronic inflammation lowers fetuin-A which is a glycoprotein that binds Ca and Phos by forming “Calciprotein particles” and helps clears the circulation form excess Ca-phos and prevent their deposition.
    Another point is the use of bisphosphinate; if the patient has a low turnover disease then it would be detrimental as Bisphosphinates would basically make the low turnover disease much worse. As the article mentions we are seeing these low turnover calciphylaxis more often;
    a 3ed point which we tend to overlook; is that CAU could be seen in both High and low turnover disease; in Both the bone is simply unavailable as a dynamic organ which normally provide an accommodation to excess ca and phos and remove them from the blood. In high turnover disease the bone is basically unable to provide a safe haven to excess ca and phs to return to the bone Bc of the constant stimulus of the parathyroid hormone. I low turnover disease the bone has simply lost all function. in the former case treatment could reverse course either through medical or surgical parathyroidectomy. in the latter however; it is irreversible and avoidance of PTH Suppression is Vital.
    My take is that we should be pragmatic, aggressive and use multidisciplinary approach with more than one modality and just as importantly avoid unnecessary or harmful therapies.
    unfortunately Bone biopsy would provide the exact nature of the bone disease but it's extremely underutilized in general.
    Ezra Hazzan

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