Cleveland Clinic Journal of MedicineExtraosseous Calcification in Kidney Disease

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Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) significantly increase the risk of extraosseous calcification, a condition encompassing vascular calcification, soft tissue calcification, and calciphylaxis. This review article outlines the current understanding of the pathogenesis, clinical presentation, diagnostic approaches, and treatment options for these disorders. The complex interplay of abnormal electrolyte levels, cell differentiation, and dysregulation of biochemical pathways contributes to the active process of extraosseous calcification in patients with kidney disease.

Key Points:

• Extraosseous calcification in kidney disease includes vascular calcification, soft tissue calcification, and calciphylaxis, with vascular calcification being the most common form.
• The pathogenesis involves dysregulation of calcium-phosphate metabolism, elevated fibroblast growth factor 23 (FGF-23) levels, and decreased klotho production.
• Vascular calcification is often diagnosed incidentally, while soft tissue calcification and calciphylaxis are typically identified through clinical presentation and radiographic findings.
• Management strategies focus on maintaining neutral calcium balance, correcting hyperphosphatemia, and controlling comorbidities, though evidence for these approaches is of low quality.
• Phosphate binders, calcimimetics, and vitamin K supplementation have shown mixed results in clinical trials for preventing or treating vascular calcification.
• Novel therapies, such as SNF472 and tissue-nonspecific alkaline phosphatase inhibitors, are in development for treating extraosseous calcification.
• Surgical debridement and hyperbaric oxygen therapy may serve as adjunctive treatments for soft tissue calcification and calciphylaxis.

HCN Medical Memo
Extraosseous calcification in chronic and end-stage kidney disease presents a significant challenge in patient management. Although current treatment strategies focus on maintaining mineral balance and controlling comorbidities, emerging therapies and ongoing research may provide more targeted approaches in the future. Clinicians should remain vigilant in monitoring for and addressing this complication to improve outcomes in patients with kidney disease.

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