Success of small-dose fractionated sodium thiosulfate in the treatment of calciphylaxis in a peritoneal dialysis patient

Background Calciphylaxis, or calcific uremic arteriolopathy (CUA), is a rare, fatal disorder of microvascular calcification and thrombosis that typically affects patients with end-stage renal disease (ESRD) receiving long-term dialysis. Fewer reports describe calciphylaxis in peritoneal dialysis patients than hemodialysis patients as per a literature review. To date, there are no clear guidelines for CUA diagnosis and treatment. While sodium thiosulfate (STS) has been increasingly used for treatment in recent years, there have also been reports of severe side effects. There is no uniform standard for its usage and dosage, especially for peritoneal dialysis patients. Case presentation We present a case of a 40-year-old Chinese male patient with ESRD on peritoneal dialysis who developed calciphylaxis with severe painful cutaneous ulcers on the fingers and toes that were managed successfully for 6 months with comprehensive treatment composed mainly of small-dose fractionated sodium thiosulfate. Conclusions Our experience suggests that the treatment of calciphylaxis requires timely and multi-angle intervention. Treatment with small-dose fractionated sodium thiosulfate has proven effective and tolerated in this patient.

Hepatic and Vascular Vitamin K Status in Patients with High Cardiovascular Risk

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r2 ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.

Role of Sodium Thiosulphate in Calciphylaxis

Calciphylaxis, also known as Calcific Uremic Arteriolopathy (CUA), is a rare condition often but not exclusively seen in end stage renal disease. Current literature recommends trial of Sodium Thiosulphate (STS) in all CUA patients. The long - term use of STS is limited by the adverse effect of Anion Gap Metabolic Acidosis (AGMA) which can be managed timely to maximize the benefits of STS.

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

Calcific uremic arteriolopathy (CUA; calciphylaxis) is a severe form of vascular calcification with no approved therapies. A standardized wound assessment tool is needed to evaluate changes in calciphylaxis wounds over time. A prospective, single-arm study of 14 patients with calciphylaxis reported improvement for the primary endpoint of wound healing using the 13-item Bates-Jensen Wound Assessment Tool (BWAT), although that tool was developed for assessment of pressure ulcers. This report describes development of BWAT-CUA, an 8-item modification of BWAT focusing on prototypical features of calciphylaxis lesions. The BWAT-CUA has a range of 8 (best) to 40 (worst) and was used ad hoc to analyze BWAT data collected in the prospective study. Using BWAT-CUA, relative improvement in calciphylaxis wounds was 30% overall (from 21.2 to 14.9; p = 0.0016) and 34% in the subset of 12 patients with ulceration at baseline (from 23.3 to 15.3; p = 0.0002). BWAT-CUA is a primary endpoint in an ongoing randomized, placebo-controlled phase 3 study of SNF472 recruiting patients with end-stage kidney disease and at least one ulcerated calciphylaxis lesion. BWAT-CUA, a newly developed tool for assessment of calciphylaxis wound severity and improvements over time, may be used in clinical research and in clinical practice.

Sequential Bone Scintigraphy and the Evolution of Warfarin-Mediated Calcific Uremic Arteriolopathy

Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a complex syndrome of deranged mineral metabolism and vascular calcification leading to tissue ischemia that primarily occurs in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). We report a case illustrating a temporal relationship between long-term warfarin anticoagulation and development of CUA in a patient with pre-dialysis chronic kidney disease (CKD) who progressed to ESRD. Serial 99mTc-methylene diphosphonate bone scintigraphy documented the evolution of metastatic CUA over a 5-month period following HD initiation. Given the temporality demonstrated here via imaging, we speculate that warfarin’s influence on vitamin K-dependent matrix Gla protein function coupled with risk factors associated with ESRD led to the development of metastatic CUA.

Calcific Uremic Arteriolopathy: A Case Series and Review from an Inner-City Tertiary University Center in End-Stage Renal Disease Patients on Renal Replacement Therapy

Background and Objectives. Calcific uremic arteriolopathy (CUA) is a rare complication seen, especially in patients undergoing renal replacement therapy (RRT) with high morbidity and mortality. CUA treatment remains challenging. The study evaluated CUA's multifaceted treatment efficacy. Materials and Methods. 24 patients with CUA and on RRT were evaluated at Detroit Medical Center from 2007 to 2016. Skin biopsy was used in almost all patients, along with the radiological and clinical findings. The patient’s clinical and paraclinical data were retrieved from the electronic medical records. The effect of treatment modalities and the underlying hyperparathyroidism management were compared to the clinical outcomes using appropriate statistical tests. Results. Twenty-one patients were on hemodialysis, two patients received renal transplants, and one patient was on peritoneal dialysis. Diabetes mellitus was the most prevalent cause of ESRD. The parathyroid hormone level (PTH) was elevated in 22 patients. Fifteen patients were diagnosed 2 weeks or more prior to skin lesion onset. Twenty-two and thirteen patients received sodium thiosulphate and cinacalcet, respectively. Patients with lower PTH and the calcium-phosphate product levels had a relatively better outcome of CUA. Conclusions. A multifaceted approach may play a role in treating CUA. Referral to a nephrologist may aid in the early diagnosis and prompt management of CUA.

Potential effect of sodium thiosulfate in calciphylaxis: remission of intractable pain

Calciphylaxis, a rare disease mainly seen in patients with chronic kidney disease, is characterised by ischaemic skin damages and excruciating pain. Calciphylaxis has poor prognosis which often results in amputation and high mortality. Although guidelines for the management of calciphylaxis are not available, sodium thiosulfate has showed efficacy in many clinical reports. We report the case of a 64-year-old advanced calciphylaxis male patient who had two amputations due to intolerable pain manifested as deteriorating ulcer. After he was treated with intravenous sodium thiosulfate (STS), his pain was significantly relieved with a healing trend of the big wound. One more amputation for the remission of intractable pain was avoided. The treatment experience indicates that sodium thiosulfate is of great value in quick pain relief and reducing suffering of calciphylaxis patients. Keywords: Calciphylaxis, Calcific uremic arteriolopathy, Painful skin ulcer, Maintenance haemodialysis, Continuous....