Successful Treatment of a Patient With Severe Calcific Uremic Arteriolopathy (Calciphylaxis) by Etidronate Disodium

doi:10.1053/j.ajkd.2006.04.062

American Journal of Kidney Diseases

Volume 48, Issue 1, July 2006, Pages 151-154

https://doi.org/10.1053/j.ajkd.2006.04.062 Get rights and content

A 59-year-old woman with a 10-year history of hemodialysis was admitted to our hospital for painful skin ulcers on her right thigh, right calf, and left upper arm. A whole-body plain computed tomographic scan showed diffuse calcification of the uterus and marked calcification of the mitral valve. Skin biopsy specimens from the left thigh showed calcium deposition in numerous small blood vessels in the dermis and fat, leading to a diagnosis of calcific uremic arteriolopathy (CUA). Despite antibiotic therapy and aggressive wound care for 2 months, the skin ulcers enlarged and the patient’s general condition worsened. Surprisingly, oral administration of etidronate disodium (200 mg/d) strikingly improved the focal infection and decreased the size of the skin ulcers within several days. She was discharged from the hospital 2 months later, when epithelialization of the ulcers was almost complete. We report a case of CUA that was improved dramatically by treatment with etidronate. Etidronate therapy should be considered for refractory CUA.

Section snippets

Case Report

A 59-year-old woman with a 10-year history of hemodialysis had had painful erythema on her legs since January 2003. Despite careful local wound care, skin lesions worsened and ulcerations developed. She was admitted to our hospital on May 16, 2003. Upon admission, multiple irregular-shaped dark red lesions with necrosis were observed on her right thigh, right calf, and left upper arm (Fig 1A). All lesions were extremely tender. Body temperature was 37.5°C, and blood pressure was 162/86 mm Hg.

Discussion

Bisphosphonates, synthetic compounds characterized by a P-C-P group, have been used mainly to inhibit bone resorption in patients with such diseases as osteoporosis, Paget disease, and hypercalcemia associated with malignancy. This suppression of bone resorption is believed to be caused by a cellular effect involving both apoptosis of osteoclasts and destruction of the osteoclastic cytoskeleton, thus inducing a decrease in osteoclast activity.⁴ However, because of an additional property of

Acknowledgment

The authors thank Dr R. Tyler Miller (Case Western Reserve University) for critical reading of the manuscript and helpful discussions.

References (17)

A. Fine et al.
Calciphylaxis is usually non-ulceratingRisk factors, outcome and therapy
Kidney Int
(2002)
D.T. Janigan et al.
Calcified subcutaneous arterioles with infarcts of the subcutis and skin (“calciphylaxis”) in chronic renal failure
Am J Kidney Dis
(2000)
K. Nitta et al.
Effects of cyclic intermittent etidronate therapy on coronary artery calcification in patients receiving long-term hemodialysis
Am J Kidney Dis
(2004)
A.H. Fischer et al.
Pathogenesis of calciphylaxisStudy of three cases with literature review
Hum Pathol
(1995)
J. Monkkonen et al.
Clodronate (dichloromethylene bisphosphonate) inhibits LPS-stimulated IL-6 and TNF production by RAW 264 cells
Life Sci
(1994)
W.A. Wilmer et al.
CalciphylaxisEmerging concepts in prevention, diagnosis, and treatment
Semin Dial
(2002)
B.R. Don et al.
A strategy for the treatment of calcific uremic arteriolopathy (calciphylaxis) employing a combination of therapies
Clin Nephrol
(2003)
H. Fleisch
Development of bisphosphonates
Breast Cancer Res
(2002)

There are more references available in the full text version of this article.

Cited by (87)

Calciphylaxis: Treatment and outlook—CME part II
2022, Journal of the American Academy of Dermatology
Citation Excerpt :
Bisphosphonates, such as etidronate disodium and pamidronate, are used to stabilize bone metabolism primarily in osteoporosis. There appears to be a beneficial effect of bisphosphonates in calciphylaxis, perhaps by reducing calcium levels, although the exact mechanism is unknown.48-50 Nephrology consultation can help determine whether initiation is appropriate, the recommended dose, and length of treatment on a case-by-case evaluation.
Calciphylaxis is a rare and devastating condition with important systemic ramifications. This second-part of our CME aims to educate the practicing dermatologist on the current standard of care once a diagnosis of calciphylaxis is confirmed or highly suspected. The key pathologic findings, as well as the role and limitations of biopsy, are reviewed. We aim to guide readers through the complex hospitalization and posthospitalization management of these medically vulnerable patients. Collaboration with other specialists will be discussed. Experimental and developing treatments are discussed, and the outlook of the condition is reported.
Treatment of Calciphylaxis in CKD: A Systematic Review and Meta-analysis
2019, Kidney International Reports
Calciphylaxis is a life-threatening complication of chronic kidney disease (CKD). To inform clinical practice, we performed a systematic review of case reports, case series, and cohort studies to synthesize the available treatment modalities and outcomes of calciphylaxis in patients with CKD.
Electronic databases were searched for studies that examined the uses of sodium thiosulfate, surgical parathyroidectomy, calcimimetics, hyperbaric oxygen therapy, and bisphosphonates for calciphylaxis in patients with CKD, including end-stage renal disease. For cohort studies, the results were synthesized quantitatively by performing random-effects model meta-analyses.
A total of 147 articles met the inclusion criteria and were included in the systematic review. There were 90 case reports (90 patients), 20 case series (423 patients), and 37 cohort studies (343 patients). In the pooled cohorts, case series, and case reports, 50.3% of patients received sodium thiosulfate, 28.7% underwent surgical parathyroidectomy, 25.3% received cinacalcet, 15.3% underwent hyperbaric oxygen therapy, and 5.9% received bisphosphonates. For the subset of cohort studies, by meta-analysis, the pooled risk ratio for mortality was not significantly different among patients who received sodium thiosulfate (pooled risk ratio [RR] 0.89; 95% confidence interval [CI] 0.71–1.12), cinacalcet (pooled RR 1.04; 95% CI 0.75–1.42), hyperbaric oxygen therapy (pooled RR 0.89; 95% CI 0.71–1.12), and bisphosphonates (pooled RR 0.77; 95% CI 0.44–1.32), and those who underwent surgical parathyroidectomy (pooled RR 0.88; 95% CI 0.69–1.13).
This systematic review found no significant clinical benefit of the 5 most frequently used treatment modalities for calciphylaxis in patients with CKD. Randomized controlled trials are needed to test the efficacy of these therapies.
A Heart of Stone: Cardiac Fibroblasts Turn to Bone in Calcified Hearts
2017, Cell Stem Cell
Citation Excerpt :
If we consider it unlikely that different tissues utilize disparate pathways for synthesizing calcium hydroxyapatite, then we would hypothesize that ENPP1 activity is a key step toward pathological calcification in general and thus, its disruption could be a strategy to prevent ectopic calcification regardless of the underlying cause. In support of this idea, drugs such as etidronate are often administered to attenuate mineralization in conditions causing accelerated calcification such as calciphylaxis in patients with chronic kidney disease (Shiraishi et al., 2006). This is an example of a clinical condition in which vascular calcification can be anticipated and thus preventative measures have the potential to provide beneficial effects.
Calcinosis cutis and calciphylaxis
2015, Actas Dermo-Sifiliograficas
La calcinosis cutis (CC) se define como el depósito de sales de calcio en la piel. Esta entidad se clasifica en 5 tipos que incluyen la CC distrófica, metastásica, idiopática, iatrogénica y calcifilaxis. La calcificación distrófica constituye el tipo más frecuente y aparece principalmente en enfermedades autoinmunes. El tratamiento de la CC incluye la extirpación quirúrgica o el uso de fármacos como diltiazem, bifosfonatos, warfarina, ceftriaxona, probenecid, minociclina e hidróxido de aluminio. La calcifilaxis se define como la calcificación de la capa media de vasos de pequeño y mediano tamaño de la dermis y tejido celular subcutáneo. Clínicamente se manifiesta como un síndrome de livedo racemosa que progresa a púrpura retiforme y necrosis cutánea. La primera línea de tratamiento es el tiosulfato sódico. El objetivo de esta revisión es proporcionar un análisis de los diferentes trastornos de calcificación cutánea enfocada en su diagnóstico y tratamiento.
Calcinosis cutis (CC) is defined as the deposition of calcium salts in the skin. The condition is divided into 5 types: calciphylaxis and dystrophic, metastatic, idiopathic, and iatrogenic CC. Dystrophic CC is the most common form and usually occurs in association with autoimmune diseases. CC can be treated surgically or with the use of drugs such as diltiazem, bisphosphonates, warfarin, ceftriaxone, probenecid, minocycline, or aluminum hydroxide. Calciphylaxis is defined as calcification of the media of small- and medium-sized blood vessels in the dermis and subcutaneous tissue. Clinically, calciphylaxis causes livedo racemosa, which progresses to retiform purpura and skin necrosis. First-line treatment is with sodium thiosulfate. We present a review of the calcifying disorders of the skin, focusing on their diagnosis and treatment.
Calciphylaxis: Risk factors, diagnosis, and treatment
2015, American Journal of Kidney Diseases
Calciphylaxis is a rare but devastating condition that has continued to challenge the medical community since its early descriptions in the scientific literature many decades ago. It is predominantly seen in patients with chronic kidney failure treated with dialysis (uremic calciphylaxis) but is also described in patients with earlier stages of chronic kidney disease and with normal kidney function. In this review, we discuss the available medical literature regarding risk factors, diagnosis, and treatment of both uremic and nonuremic calciphylaxis. High-quality evidence for the evaluation and management of calciphylaxis is lacking at this time due to its rare incidence and poorly understood pathogenesis and the relative paucity of collaborative research efforts. We hereby provide a summary of recommendations developed by a multidisciplinary team for patients with calciphylaxis.
Adynamic Bone Disease: From Bone to Vessels in Chronic Kidney Disease
2014, Seminars in Nephrology
Adynamic bone disease (ABD) is a well-recognized clinical entity in the complex chronic kidney disease (CKD)–mineral and bone disorder. Although the combination of low intact parathyroid hormone (PTH) and low bone alkaline phosphatase levels may be suggestive of ABD, the gold standard for precise diagnosis is histomorphometric analysis of tetracycline double-labeled bone biopsies. ABD essentially is characterized by low bone turnover, low bone volume, normal mineralization, and markedly decreased cellularity with minimal or no fibrosis. ABD is increasing in prevalence relative to other forms of renal osteodystrophy, and is becoming the most frequent type of bone lesion in some series. ABD develops in situations with reduced osteoanabolic stimulation caused by oversuppression of PTH, multifactorial skeletal resistance to PTH actions in uremia, and/or dysregulation of Wnt signaling. All may contribute not only to bone disease but also to the early vascular calcification processes observed in CKD. Various risk factors have been linked to ABD, including calcium loading, ageing, diabetes, hypogonadism, parathyroidectomy, peritoneal dialysis, and antiresorptive therapies, among others. The relationship between low PTH level, ABD, increased risk fracture, and vascular calcifications may at least partially explain the association of ABD with increased mortality rates. To achieve optimal bone and cardiovascular health, attention should be focused not only on classic control of secondary hyperparathyroidism but also on prevention of ABD, especially in the steadily growing proportions of diabetic, white, and elderly patients. Overcoming the insufficient osteoanabolic stimulation in ABD is the ultimate treatment goal.

View all citing articles on Scopus

Originally published online as doi:10.1053/j.ajkd.2006.04.062 on June 5, 2006.

Support: None. Potential conflicts of interest: None.

View full text

Case ReportSuccessful Treatment of a Patient With Severe Calcific Uremic Arteriolopathy (Calciphylaxis) by Etidronate Disodium

Section snippets

Case Report

Discussion

Acknowledgment

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Hum Pathol

Life Sci

CalciphylaxisEmerging concepts in prevention, diagnosis, and treatment

Semin Dial

A strategy for the treatment of calcific uremic arteriolopathy (calciphylaxis) employing a combination of therapies

Clin Nephrol

Development of bisphosphonates

Breast Cancer Res

Case Report
Successful Treatment of a Patient With Severe Calcific Uremic Arteriolopathy (Calciphylaxis) by Etidronate Disodium