Calciphylaxis in end-stage kidney disease: outcome data from the United Kingdom Calciphylaxis Study

Abstract

Background and aims Calciphylaxis is a rare condition associated with very high mortality in patients with end-stage kidney disease. Data from country-based registries have been an invaluable resource for a better understanding of the natural history and management for this condition. This study aimed to investigate the current management strategies and outcomes of patients enrolled in the United Kingdom Calciphylaxis study (UKCS). Methods The study was conducted on 89 patients registered in the UKCS since 2012. The initial analysis included a description of the baseline characteristics, management strategies and outcomes on follow-up until May 2020. Further analysis included a comparison of the mortality outcome of the UKCS patients who were receiving haemodialysis with a propensity score matched cohort of haemodialysis patients from the Chronic Renal Insufficiency Standards Implementation Study- Haemodialysis (CRISIS-HD). Results Median age of the cohort was 59 years, with a predominance of females (61%) and Caucasian (95%) ethnicity. About 54% of the patients were diabetic and 70% were receiving haemodialysis at study entry. The skin lesions were mostly distributed in the lower extremities (48%). Sodium thiosulphate and calcimimetic were the most widely used management strategies. The mortality rate was 72 deaths per hundred patient-years (50 deaths observed in 69.5 patient years). Complete wound healing was noted in 17% and bacteraemia was reported in 26% of patients. In a comparative analysis of the matched haemodialysis patients, the presence of calciphylaxis in 62 patients showed a strong association with all-cause mortality (HR 6.96; p < 0.001), with annual mortality 67% versus 10.2% in haemodialysis patients without calciphylaxis. Conclusions This UK wide study strengthens the evidence that calciphylaxis is a strong and independent risk factor associated with all-cause mortality; no significant benefit was shown with any individual treatment modality. Until further evidence becomes available, a multifaceted approach would be the appropriate treatment strategy in the management of this extremely serious condition. Graphic abstract

The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis

“…Several studies have reported 1-year mortality rates in patients with calciphylaxis at 40–50% or higher [ 11–14 ]. A recent analysis of the UK Calciphylaxis Registry reported a 1-year mortality rate of 67% versus 10% in patients receiving dialysis without calciphylaxis [ 10 ]. Patients with calciphylaxis also have a high morbidity burden and poor quality of life (QoL) related to painful wounds, ambulatory difficulties and frequent hospitalizations [ 15 , 16 ].…”

Development of the BWAT-CUA Scale to Assess Wounds in Patients with Calciphylaxis

“…Patients with calciphylaxis also have increased susceptibility to wound infections, which are ultimately responsible for approximately 50% of mortality associated with calciphylaxis [11,12]. Calciphylaxis in patients with ESKD can be a life-threatening condition, with 1-year mortality rates exceeding 45% [9,11,13,14], and calciphylaxis independently increases the risk of death by up to 8-fold [5,6,14].…”

“…In contrast, the majority of calciphylaxis lesions are highly inflammatory chronic wounds, with a local ischemic component that inhibits the progression from the inflammatory to the proliferative phase. Given the severity of the ulcers and the co-morbidities that are common in patients with calciphylaxis, complete wound healing may be delayed and complicated by superinfection, sepsis, and death [14,16,17].…”

“…Major challenges in the management of calciphylaxis include difficulty achieving pain control, poor wound healing, the lack of treatment options with demonstrated benefit, and the need for standardized methods to diagnose and monitor the progression of the characteristic wounds. Observational studies have shown that a minority of patients with calciphylaxis wounds achieve complete healing with current standard care [14,16,17]. Clinical care of patients with calciphylaxis includes topical wound care with measures to prevent infection, pain management, and various measures that are designed to reduce calcium deposition indirectly.…”

“…Clinical care of patients with calciphylaxis includes topical wound care with measures to prevent infection, pain management, and various measures that are designed to reduce calcium deposition indirectly. To date, no therapeutic interventions including parathyroidectomy, altering dialysis regimen, off-label use of sodium thiosulfate or treatment with hyperbaric oxygen have been shown to improve wound healing in any published, randomized, controlled clinical trials [2,14,[18][19][20][21][22][23][24].…”