Hyperbaric oxygen as effective adjuvant therapy in the treatmentof distal calcific uraemic arteriolopathy.

Abstract

Calcific uraemic arteriolopathy (CUA), calciphylaxis or uraemia of small-vessel disease is a rare life-threatening complication predominantly affecting patients with end-stage renal disease (ESRD) [1]. It typically occurs in those with secondary hyperparathyroidism and is associated with deranged calcium and phosphate metabolism. Other factors, such as malnutrition, obesity, diabetes mellitus, warfarin therapy and female gender, have been implicated as additional risk factors [2]. CUA presents as severely painful ulcers, usually occurring in the lower limbs. The mechanism of injury appears to be calcification of subcutaneous tissues and small arterioles. At a molecular level, derangement of vascular smooth muscle cell function leading to osteogenic differentiation in conjunction with endothelial cell dysfunction appears to be important [3]. The lesions are slow to heal, with superimposed bacterial infection leading to sepsis, the most common cause of death (in up to 80% of patients). The first case series of CUA was published in 1976 [4]. Subsequently, the incidence of CUA in patients with ESRD has increased markedly [3]. Reports to the Australia and New Zealand Dialysis and Transplantation Registry (ANZDATA) demonstrate that CUA had been identified as a comorbidity or cause of death in 171 patients, from its first documentation in 1985 until March 2005 (Figure ​(Figure1).1). Despite an increasing awareness of this disease and a better understanding of its aetiology, an effective form of treatment remains elusive. Most therapeutic regimens include aggressive wound care, ensuring adequate nutrition, improving calcium–phosphate balance and correcting secondary hyperparathyroidism. The use of bisphosphonates [5], low-molecular weight heparin [1] or sodium thiosulfate [6] has been met with success in a few patients. Fig. 1 The number of patients with ESRD and CUA as a comorbidity or cause of death reported to ANZDATA between 1985 and 2005. Hyperbaric oxygen (HBO) involves breathing 100% oxygen within a pressurized environment. It is first-line therapy for a number of medical conditions, namely decompression sickness and carbon monoxide poisoning [7]. Most recently, HBO has been shown to be of benefit in advancing wound healing, including lesions due to CUA [8]. It is proposed to work by increasing oxygen tension in the ischaemic tissue, although the primary initiating factor of vascular calcification is not altered. We report our experience with the treatment of CUA with HBO, which appears to be well tolerated. We describe the largest, single-centre case series of patients with CUA successfully treated with a combination of therapies including HBO.