Cleveland Clinic Journal of MedicineExtraosseous Calcification in Kidney Disease

Elucidating the Complex Interplay of Factors in Extraosseous Calcification Among End-Stage Kidney Disease Patients

This comprehensive review looks into the intricate mechanisms and clinical implications of extraosseous calcification in patients with chronic and end-stage kidney disease. It highlights the multifaceted pathogenesis, varying clinical presentations, and the current state of diagnostic approaches and management strategies, showcasing the active nature of the calcification process and its significant impact on patient outcomes.

Key Points:

• Extraosseous calcification encompasses vascular calcification, soft tissue calcification, and calciphylaxis, predominantly observed in end-stage kidney disease patients.
• The pathogenesis involves a dynamic interplay of altered electrolyte levels, cell differentiation, and the dysregulation of various biochemical pathways.
• Diagnostic methods vary: vascular calcification is often found incidentally, whereas soft tissue calcification and calciphylaxis require radiographic and clinical assessment, sometimes complemented by biopsy.
• Management strategies focus on maintaining calcium balance, addressing hyperphosphatemia, and managing comorbid conditions, though evidence supporting these approaches is of low quality.
• Chronic kidney disease, particularly when progressing to end-stage, leads to systemic disorders including abnormal serum levels of calcium, phosphate, PTH, and vitamin D, alongside disruptions in bone metabolism.
• Regulatory hormones from multiple organs maintain serum calcium and phosphate levels, with PTH playing a central role in balancing these minerals.
• In chronic kidney disease, the loss of nephrons escalates phosphate levels, which in turn increases FGF-23 production, contributing to bone mineral disease onset.
• Vascular calcification in kidney disease patients starts earlier compared to the general population, driven by factors like hyperphosphatemia and positive calcium balance.
• Soft tissue calcification’s clinical presentation varies, with tumoral calcinosis involving substantial calcium phosphate deposits in periarticular areas.
• Clinical management includes dietary phosphate restriction, use of phosphate binders, and in some cases, interventions like sodium thiosulfate and vitamin K supplementation, though evidence varies in effectiveness.

HCN Medical Memo
As chronic kidney disease progresses, it leads to higher rates of bone mineral disease, a systemic disorder involving abnormalities in serum calcium, phosphate, parathyroid hormone (PTH), and vitamin D levels, significantly impacting patient mortality rates.

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