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Abstract: TH-OR39

Role of Plasma Inorganic Pyrophosphate in Calciphylaxis: A Prospective Study

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Chewcharat, Api, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Bouchouari, Houda, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Krinsky, Scott, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Howe, Jennifer, Inozyme Pharma, Boston, Massachusetts, United States
  • Torcatti, Jeanfranco, Inozyme Pharma, Boston, Massachusetts, United States
  • Cizman, Borut, Inozyme Pharma, Boston, Massachusetts, United States
  • Sabbagh, Yves, Inozyme Pharma, Boston, Massachusetts, United States
  • Nigwekar, Sagar U., Massachusetts General Hospital, Boston, Massachusetts, United States
Background

Calciphylaxis is a devastating disorder characterized by painful skin lesions caused by calcific microvascular occlusion and no approved treatment. In experimental models and genetic disorders, deficiency of pyrophosphate (PPi) is linked with vascular calcification and neointimal proliferation. This study was conducted to investigate the influence of plasma PPi on severity and outcomes in calciphylaxis.

Methods

In this prospective study, we enrolled 70 patients with calciphylaxis. Plasma PPi levels were measured using an ATP Sulfurylase/Luminescence-based method at enrollment (n=70) and at 6-week follow up (n=30). We examined the associations of 1) PPi levels at enrollment with skin lesion count, pain severity (assessed by Brief Pain Inventory), and 6-week mortality, and 2) change in PPi levels over 6-week period after enrollment with 12-week mortality.

Results

Median age of our cohort was 60 years and 67% of patients had end-stage kidney disease. Median skin lesion count was 3 [IQR: 2-4] and median pain severity score was 5 [IQR: 4-7]. Median PPi levels were 568 nM [IQR: 253-1205] at enrollment and 1155 nM [IQR: 835-1456] at 6-week follow up. At enrollment, there were modest negative associations of PPi with skin lesion count (r=-0.26) and pain severity (r=-0.28). Mortality at 6 weeks was 21%. Among patients who died by 6-week follow up, PPi levels at enrollment were 66% lower compared to patients who were alive (p=0.002) (Fig). In adjusted models, for every 100 nM decrease in PPi at enrollment, there was 25% increased risk of 6-week mortality. Decrease in PPi levels over 6-week period since enrollment was associated with increased 12-week mortality (p=0.04).

Conclusion

Our novel findings demonstrate the potential of PPi as a target for therapies aimed at improving patient-oriented and clinical outcomes in calciphylaxis.

Plasma PPi and mortality in Calciphylaxis

Funding

  • Commercial Support – Inozyme Pharma