Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare disorder characterized by calcification of the small blood vessels of the skin and subcutaneous fat. It most commonly occurs in patients with end-stage renal disease on dialysis. The calcification leads to reduced blood flow and painful skin lesions. Risk factors include hyperparathyroidism, vitamin D use, and warfarin use. Diagnosis is made clinically and confirmed with biopsy showing vessel calcification. Treatment involves sodium thiosulfate, hyperbaric oxygen, bisphosphonates, and wound care. Prognosis is poor with high mortality rates due to complications like infection and organ failure.

1. CALCIPHYLAXIS(CUA)
Calcific Uraemic Arteriolopathy
ADD SOME
RELATED
PICTURE

2. OUTLINES
• INTRODUCTION
• PATHOGENESIS
• EPIDEMIOLOGY
• RISK FACTORS
• NON ESRD POPULATION
• CLINICALFEATURES
• DIAGNOSIS AND DD
• LAB MANIF/BIOPSY/ RADIOLOGY
• TREATMENT
• OUTCOME

3. CALCIFIC URAEMIC ARTERIOLOPATHY
Introduction
• CUA or calciphylaxis is a rare disorder (Orphan disease)of
microvascular occlusionof subcutaneous adipose tissue &
dermis leading to painful skin lesions- Calciphylaxis Cutis
/Visceral Calciphylaxis.
• Associated histologically with media calcification of small
& medium-size vessels in dermis & subcutaneous adipose
tissue
• Has an estimated incidence of <1% among dialysis patients
who are predominantly affected cohort

5. EPIDEMIOLOGY-RELEVANCE
• Calciphylaxis most commonly occurs in patients of ESRD
and are on dialysis but may also occur in kidney tx
recipients & in non-ESRD patients
• Is a lethal disease with an estimated six-month survival
of approx 50% with no approved RX

8. NON UREMIC CALCIPHLAXIS
60% had been previously treated with glucocorticoids, and 25% with warfarin
•Nigwekar SU, Wolf M, Sterns RH, Hix JK. Calciphylaxis from nonuremic causes: a systematic review. Clin J Am Soc
Nephrol 2008; 3:1139.

11. Severe sec HPT /vascular calcif

12. PATHOGENESIS
Calciphylaxis is a poorly understood disorder.
The skin lesions of calciphylaxis result from
reductions in the arteriolar blood flow.
Reduced blood flow is caused by calcification,
fibrosis, and thrombus formation primarily
involving the dermo-hypodermic arterioles
Hyperparathyroidism, deficiencies in inhibitors of
vascular calcification, and chronic inflammation
have also been implicated in the pathogenesis of
calciphylaxis

13. PATOGENESIS
• Microvascular calcification occurs first likely via an
active process involving up regulation of factors
involved in osteogenesis and bone remodeling,
including bone morphogenetic protein 2 (BMP-2),
runt-related transcription factor 2 (RUNX-2) and
osteopontin
• Adipocytes may also play an important role in the
development of vascular calcification of calciphylaxis .
• Ongoing vascular endothelial injury causes cutaneous
arteriolar narrowing and thrombosis leading to tissue
infarction

14. PATHOGENETIC FACTORS
• Factors presumed to be involved in the widespread
calcification are
- Chronic kidney disease-mineral bone disorder (CKD-
MBD) and its treatment (including hyper
parathyroidism, abnormalities in calcium and
phosphate, and vitamin D administration)
- Deficiencies of the inhibitors of vascular calcifications
and chronic inflammation

17. Clinical recognition
• Typical sites- high fat tissue area
• Typical appearance – early red to violet/later
black
• Typical symptom- extremely painful
• Typical risk factors- esrd/warfarin/ autoimm
• Atypical sites need DD

18. What do we see and where?
Time of presentation – Early -late.
• Mottled skin (livedo reticularis)- Violaceous/red
• Purpuric plaque-like subcutaneous nodules, indurations
• Bullae over plaque ,Necrotic ulcers with eschars
(skin/subcutaneous fat/ muscle)
• Typical lesions seen more in central body area than on
finger and toes (areas with high adipose tissue content)

19. Followed the path of the vasculature
Intense pain is a constant finding

21. Digital gangrene in a dialysis patient due to calciphylaxis and systemic
polyarteritis nodosa: A diagnostic dilemma
Jain N; Sethi J; Ramachandran R; Kumar V; Rathi,M, et al.
Ind J of Nephrology 2019
Left foot gangrenous changes and
redness swelling of all toes with
ulcer on dorsal aspect

23. Differential diagnosis
 Many dermatologic conditions resemble the superficial lesions of
Calciphylaxis
Diagnosis Distinguishing characteristic(s)
Antiphospholipid
syndrome
Serum antiphospholipid antibodies
Radiation arteritis Radiation arteritis
Vasculitis Significant inflammatory infiltrate
Dystrophic
calcification
Localized tissue damage secondary to calcium and
phosphorous deposition; normal serum calcium and
phosphorous levels
Cholesterol emboli Acute onset; biopsy shows cholesterol crystals embedded
within intramural thrombi; lesions distributed in extremities
with acral involvement

24. Differential diagnosis
Diagnosis Distinguishing characteristic(s)
Panniculitis Biopsy reveals inflammatory infiltrate in the adipose tissue
without calcification of vessels
Purpura fulminans Sepsis and disseminated intravascular coagulation often
present; increased partial thromboplastin time, prothrombin
time, fibrinogen, D-dimers
Warfarin necrosis History of warfarin use
Heparin necrosis History of heparin use; occurs uniquely at sites of
intramuscular heparin injection
Atherosclerosis
obliterans
Affects intimal layer of the abdominal aorta and small- to
medium-sized arteries in the lower extremities, often
resulting in elimination of the popliteal, posterior tibial,
and/or dorsalis pedis pulses

25. Histological features on Biopsy
• Calcification of medial wall of arterioles dermo-
hypodermal and pannicular region
• Intimal proliferation & fibrosis, endovascular
thrombosis
• Ischaemic pathology distal to vessels

26. Role of Imaging in diagnosis
• Plain X Ray/3D CT/ Mammography-limited role
Demonstrates an arborisation of vascular calcification within
the dermis and the subcutaneous tissue &numerous
echogenic foci suggestive of large calcifications-best detected
by mammoographic technique or CT reconstruction rather
than plain xray
• BONE SCAN OR SCINTIGRAPHY
Three-phase technetium 99m methylene diphosphate bone
scan to identify cutaneous calcifications

27. Role of Imaging in diagnosis
• X-ray : Detects vascular calcification within the dermis
and subcutis
- “ Net-like”
- Mammography film better detects small vessels
• Bone scintigraphy :
-Scans entire body
-Detects micro calcificatio of soft tissue
-Evaluates extent of disease and response to treatment
-89% sensitivity,97% specificity

29. Bone scintigraphy
Demonstrate bone
matrix protein
osteopontin

30. Multi-disciplinary care
Treating calcification,ulcer,pain,supportivemeasures

31. Treatment of Calciphylaxis
• Optimising dialysis adequacy
• Sodium thiosulfate (off-label use)
• PD to HD transition
• Hyperbaric oxygen therapy
• Bisphosphonates

32. Sodium Thiosulphate
• Currently, the first-line treatment of calciphylaxis
without secondary HPT
• It is a potent antioxidant and it also increases the
solubility of calcium deposits
• It causes rapid pain relief and successful wound
healing within weeks to months of initiating therapy
• Median-duration-96days(median-no38days)in
literature

33. Dose
• Dose: 25 g iv 3 times per week following dialysis
• Infusion times vary from 30-60 minutes in last h
of hd
• Reduce the dose of STS to 12.5 g for patients
weighing <60 kg and those weighing ≥60 kg who
cannot tolerate the higher dose. One should stop
STS in patients who fail to respond to STS within
the first two to four weeks.

34. Hyperbaric oxygen
• Breathing 100% O2 at higher than ambient pressure
inside a sealed chamber
1.5 to 2 hours a day 3-5/week
• Most often used for hypoxia wounds , CO poisoning , gas
emboli ,scuba diving injury “ the bends” smoke
inhalation
• Restoration of tissue PO2 to normal/above-normal
fibroblast proliferation , collagen
production,angiogenesis,reduced anaerobic colonization
improved phagocytosis.
25-30 SESSIONS
NEEDED

35. Auxiliary Management
• Discontinue all medications that may contribute to
calciphylaxis, including vitamin D, calcium
supplements, warfarin, and iron.
• Kidney transplant patients may require adjustment of
therapy with specific attention to avoiding agents that
delay wound healing-like sirolimus/everolimus/steroid
• 1 mg/kg enoxaparin twice daily demonstrated efficacy in
calciphylaxis ulcer healing.
• 10 mg tissue plasminogen activator (tPA) for 14 days iv.
is beneficial in hypercoagulable state

36. Combination Treatment
• Sodium thiosulfate in combination with hyperbaric oxygen
therapy has shown efficacy.
• Combination therapies such as sodium thiosulfate with
Cinacalcet and sodium thiosulfate with bisphosphonates are
currently being investigated.
• Two possible molecular targets are Fetuin-A and Matrix Gla,
both of which are vascular calcification inhibitorsare
research approaches

37. Summary of treatment approaches

38. Complications
• Complications of calciphylaxis range from moderate
interference with activity to death.
• Lesions of calciphylaxis frequently result in nonhealing ulcers
and cutaneous gangrene.
• Acral lesions may fail to heal with conservative therapy and
lead to amputation. Sepsis may result from the non healing
wounds.
• Patients with internal involvement may develop
gastrointestinal haemorrhage, infarction, or organ failure.
• Patients who do not die of sepsis or organ failure frequently
undergo amputation of an involved limb.

39. Take home message
• Clinical picture is sufficient to diagnose CUA in
most cases
• There are high number of missed,
undiagnosed cases
• Optimize the dialysis prescription
• Sodium thiosulfate is a first-line treatment
option
• Bisphosphonates is another treatment option

40. Take home message
• Parathyroidectomy /cinacalcet are options in CUA
• CUA treatment should be multimodal
• Stopping vitamin K antagonist should be
considered
• Vitamin K supplementation may be considered
• Prognosis of CUA is poor(1&5y survival rates
estimated to be 45% & 35%)
• Lack of evidence does not justify neglect:how can
we address unmet needs in calciphylaxis?

41. THANK YOU