Nephrol Dial Transplant (2008) 23: 387–389
doi: 10.1093/ndt/gfm676
Advance Access publication 2 October 2007
Case Report
Proximal calciphylaxis treated with calcimimetic ‘cinacalcet’
Ismail A. Mohammed1 , Vashisht Sekar2 , Abdullah J. Bubtana1 , Sandip Mitra1 and Alastair J. Hutchison1
1
Department of Renal Medicine, Manchester Royal Infirmary, Manchester, UK and 2 Academic Surgery Unit, University of
Manchester, Manchester, UK
Keywords: calciphylaxis; end stage renal failure;
haemodialysis; hyperparathyroidism; cinacalcet;
metastatic calcification
Introduction
Calciphylaxis is a rare but potentially fatal condition,
characterized by painful purpuric skin lesions, subcutaneous nodules and necrotic ulceration. The disorder occurs
mostly in patients with end-stage renal failure on dialysis
or after kidney transplantation associated with secondary
or tertiary hyperparathyroidism [1–4]. The correct treatment of caciphylaxis is controversial but most authorities
recommend parathyroidectomy for patients with high
parathyroid hormone (PTH) levels. Parathyroidectomy
improves wound-healing and increases survival rate [3–5].
However, parathyroidectomy is not without its complications in addition to anaesthetic risk, which often preclude
surgery in a subgroup of patients. In this group of patients, medical treatment with Cinacalcet represents a potential alternative. Clinical trial results have proven that
Cinacalcet reduces PTH as well as calcium and phosphate
in haemodialysis patients with secondary hyperparathyroidism [6,7]. Nonetheless, evidence for Cinacalcet efficacy in treatment of calciphylaxis is sparse and anecdotal.
Here we report a case of proximal calciphylaxis in a
76-year-old lady who was successfully treated with the
calcimimetic ‘Cinacalcet’.
Correspondence and offprint requests to: Ismail A. Mohammed,
Registrar in Renal Medicine, Manchester Royal Infirmary, Oxford
Road, Manchester M13 9WL, UK. Tel: +0161-291-6359; E-mail:
[email protected]
Case report
A 76-year-old Caucasian lady with end-stage renal failure
secondary to diabetic nephropathy, treated with thrice
weekly haemodialysis presented in June 2005 with multiple
painful lumps and ulceration over the lower abdomen and
thighs. A few months prior to presentation, she noted a
6 kg loss in body weight and complained of a constant
dull aching pain over the left hip region. The patient had
a long-standing history of type 2 diabetes mellitus, secondary hyperparathyroidism, ischaemic heart disease, and
previous uterine neoplasia, but no history of arthritis or skin
rash.
On presentation, her medication included atenolol 25 mg
once daily, alfacalcidol 0.5 mcg daily, sevelamer hydrochloride 800 mg thrice daily, calcichew 1.25 g twice daily,
omperazole 20 mg once daily, insulin and aspirin 75 mg
once daily; she was not treated with warfarin or heparin.
Physical examination revealed an obese lady (BMI 31.5),
with multiple violaceous lesions over the abdomen and
thighs which were extremely tender on palpation. There
was a painful 5 cm × 3 cm necrotic ulcerated area surround by erythema on the right lower abdomen (Figure 1).
A similar ulcer of 3 cm × 2 cm was also noted on the
left thigh. The peripheral pulses were normally felt on the
lower limbs. A tender hard swelling could easily be felt
on the left hip. The rest of her systemic examination was
unremarkable.
Laboratory data revealed normal haematocrit,
haemoglobin, white blood count, and platelets. Her blood
chemistry was consistent with a patient with established
renal failure on haemodialysis. Corrected plasma calcium
was 2.47 mmol/l, phosphate: 1.97 mmol/l, alkaline
phosphatase: 167 IU/l (reference range: 25–110 IU/l),
albumin: 30 g/l, intact PTH: 997 pg/ml (reference range:
15–65 pg/ml) and CRP: 62 mg/l. Cryoglobulin, antinuclear
antibodies and antineutrophil cytoplasmic antibodies were
all negative. Multiple blood and wound swab cultures were
also negative.
Radiology of the left hip showed huge tumour-like calcification on the left hip area, as well as calcified left femoral
artery (Figure 1). There was also extensive calcification
affecting the splenic, mesenteric, external iliac, profunda
femoris and brachial arteries.
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Abstract
Calciphylaxis is a rare condition affecting patients suffering
from end-stage renal failure, characterised by cutaneous
ischaemia and necrosis. The management of calciphylaxis
is challenging owing to the lack of optimal medical therapy,
although parathyroidectomy has shown some benefit. We
present a case of severe proximal calciphylaxis treated with
a small dose of the calcimimetic ‘Cinacalcet’.
388
Fig. 1. Abdominal ulceration due to calciphylaxis (left) with evidence of
huge left hip tumour-like calcification.
I. A. Mohammed et al.
Fig. 3. Complete healing of abdominal ulceration (due to calciphylaxis) and regression of tumour-like calcification following treatment with
Cinacalcet.
(Figure 3). She remained in good heath until March 2007,
when she died from a cerebrovascular accident.
Fig. 2. Intact PTH levels during the course of treatment with Cinacalcet
(treatment commenced in August 2005).
A diagnosis of proximal calciphylaxis was made on
clinical grounds, and treatment commenced with analgesia, antibiotics, local wound care and phosphate binders
(sevelamer hydrochloride and calcichew). The patient
was assessed for parathyroidectomy but was considered unsuitable, owing to her co-morbidities. Instead,
in August 2005, she was commenced on Cinacalcet
30 mg/day orally. Over the following 2 months, her parathyroid levels reduced to 264 pg/ml, serum phosphate normalized, corrected calcium fell to 2.02 mmol/l and ulcers began
healing with granulation. By the end of the 4th month, her
PTH value fell to 98 pg/ml (Figure 2) with complete healing
of both abdominal and thigh ulcers (Figure 3). Interestingly,
the patient’s anginal pain seemed to have stabilized, with
less frequent attacks and need for medication. She was
maintained on Cinacalcet 30 mg/day. A year later, while on
Cinacalcet 30 mg/day, a follow-up X-ray showed remarkable regression in the size of the left hip region calcification
Calciphylaxis is the ischaemic ulceration of the skin due
to metastatic calcification of the subcutaneous tissue and
small arteries in patients with end-stage renal failure.
Hyperparathyroidism has been suggested to be a risk factor but some cases of calciphylaxis with normal or even
low PTH levels have been reported [8]. The incidence of
calciphylaxis in dialysis patients is estimated at 1%/year,
with a reported prevalence of 4% [9]. Calciphylaxis is a potentially lethal disease, with a high mortality rate (60–80%)
principally due to ischaemic events and sepsis complicating
secondary infection of the ulcers [10]. Diagnosis of calciphylaxis require high index of suspicion in a patient with
end-stage renal failure with typical skin lesions, as there
are no specific laboratory tests. Skin biopsy is specific and
can establish the diagnosis, but is not pathognomonic.
Proximal calciphylaxis with lesions affecting the
abdomen, thighs and buttocks carries a poor prognosis
(63% mortality rate) compared to distal lesions (23%
mortality rate) [4]. White race, female gender, recent loss of
weight, morbid obesity and poor nutrition are reported risk
factors associated with proximal calciphylaxis [11]. Our
patient’s lesions appeared proximally with similar characteristics, including female sex, low serum albumin, recent
weight loss and Caucasian ethnicity. In this case, diagnosis
of calciphylaxis was suggested by the characteristic skin
lesions without performing a skin biopsy.
Therapeutic options for calciphylaxis are limited, unsatisfactory and essentially supportive, involving calcium and
phosphate control, parathyroidectomy and local wound care
[12]. Vassa et al. recommend treatment of calciphylaxis
ulcers with hyperbaric oxygen [13,14]. Experience with
calcimimetics in the treatment of calciphylaxis is sparse and
limited to a few case reports. Velasco et al. reported a case
of distal calciphylaxis successfully treated with Cinacalcet
as an alternative to parathyroidectomy [15]. In his report,
treatment with Cinacalcet 60–120 mg/day for a period of
9 months reduced PTH levels with resolution of the distal
leg ulcers. In our patient however, a small dose of Cinacalcet
(30 mg/day) normalized PTH values with complete healing
of abdominal and thigh ulcer within a relatively short period
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Discussion
Proximal calciphylaxis treated with calcimimetic ‘Cinacalcet’
Conflict of interest. No part of this manuscript has been published before
either in part or whole by any of the authors.
References
1. Adrogue HJ, Frazier MR, Zeliff B et al. Systemic calciphylaxis
revisited. Am J Nephrol 1981; 1: 177–183
2. Coates T, Kirkland GS, Dymock RB. Cutanous necrosis from calcific
arteriopathy. Am J Kidney Dis 1998; 32: 384–391
3. Girtto JA, Harmon JW, Patner LE et al. Parathyroidectomy promotes
wound healing and prolongs survival in patients with calciphylaxis
from secondary hyperparathyroidism. Surgery 2001; 130: 645–651
4. Hafner J, Kuesh G, Wahl C et al. Uremic small-small artery disease with medial calcification and intimal hyperplasia (so-called
calciphylaxis): a complication of chronic renal failure and benefit
from parathyroidectomy. J Am Acad Dermatol 1995; 33: 954–962
5. Gipstein R, Coburn J, Adams D et al. Calciphylaxis in man. A
syndrome of tissue necrosis and a vascular calcification in 11 patients
with chronic renal failure. Arch Intern Med 1976; 136: 1273–1280
6. Linberg JS, Meo SM, Goodman WG et al. The calcimimetic AMG
073 reduces parathyroid hormone and calcium x phosphate in
secondary hyperparathyroidism. Kidney Int 2003; 14: 575–583
7. Block GA, Martin KJ, de Francisco AL et al. The calcimimetic
cinacalcet hydrochloride (AMG 073) for treatment of secondary
hyperparathyroidism in haemodialysis patients. N Engl J Med 2004;
350: 1516–1525
8. Fader DJ, Sang S. Calciphylaxis without renal failure. Arch Dermatol
1998; 132: 873–878
9. Angelis M, Wong Sa, Wong LM. Calciphylaxis in haemodialysis: a
prevalence study. Surgery 1997; 122: 1083–1089
10. Chan YL, Mahony JF, Turner JJ et al. The vascular lesions associated
with skin necrosis in renal disease. Br Dermatol 1983; 109: 85–95
11. Bleyer A, Choi M, Igwemezie B et al. A case control study of proximal
calciphylaxis. Am J Kidney Dis. 1998; 32: 3676–3683
12. Don BR, Chin AI. Strategy for the treatment of calcific uremic
arteriopathy (calciphylaxis) employing a combination of therapies.
Clin Nephrol. 2003; 59: 463–467
13. Vassa N, Twardowski ZJ, Campbell J et al. hyperbaric oxygen therapy
in calciphylaxis induced necrosis in peritoneal dialysis patients. Am.
J Kidney Dis. 1994; 23: 878–881
14. 14-Basile C, Montanaro A, Masi M et al. Hyperbaric oxygen therapy
for calcific uraemic arteiopathy: a case series. J Nephrol 2002; 15:
676–680
15. Velasco N, Mac Gregor MS, Innes A et al. Successful treatment of
calciphylaxis with cinacalcet—an alternative to parathyroidectomy?
Nephro Dial Transplant 2006 Jul; 21(7): 1999–2004. Epub 2006
Apr 7
16. Gerakis A, Hutchison AJ, Apostolou Th et al. Biochemical markers
for non-invasive diagnosis of hyperparathyroid bone disease and
adynamic bone in patients on haemodialysis. Nephro Dial Transplant
1996; 11: 2430–2438
Received for publication: 31.5.07
Accepted in revised form: 4.9.07
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of 20 weeks. Furthermore, following a one-year treatment
with Cinacalcet, we noticed a regression in the size of tumour calcification at the left hip region (Figure 3). Although
parathyroidectomy reduces the intact PTH level to zero or
close to zero, we do not know what degree of suppression by Cinacalcet is required to be similarly successful.
On one hand, it is not sensible to reduce PTH to zero, but
on the other hand, we know that inadequate suppression
would probably not halt the skin necrosis. Therefore, we
opted to treat to a PTH of approximately 100 pg/ml (98
pg/ml). While low PTH levels are associated with adynamic bone, in our patient’s case we thought it was safer
to over- rather than under-suppress. Furthermore, it is well
recognised that even with PTH levels in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) range of 150–300 pg/ml, many patients
may have adynamic bone [16].
In conclusion, our case demonstrates the beneficial
therapeutic effect of Cinacalcet in the treatment of proximal calciphylaxis with secondary hyperparathyroidism.
Apart from mild asymptomatic hypocalcaemia, there were
no reported side effects. The drug appears to be safe and
well-tolerated over a treatment period of 18 months. We
recommend using Cinacalcet to treat calciphylaxis in highrisk surgical patients, or in those who do not wish surgery;
however, further clinical trials are needed to confirm this
effect.
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