Metastatic Calcification


  • History: metastatic calcification (aka “Calciphylaxis”) is a poorly understood and highly morbid syndrome of vascular calcification and skin necrosis
    • Bryant and White first reported it in association with uremia in 1898
  • Incidence/Prevalence:
    • 60% of chronic dialysis patients have metastatic calcification on autopsy (this is the largest patient population affected by metastatic calcification)
      • Metastatic calcification affects 1-4% of the population with ESRD
      • Metastatic calcification has increased during the last decade possibly due to more widespread use of parenteral vitamin D and iron dextran
      • No good data are available regarding the incidence of metastatic calcification in the general population without ESRD, but it is probably exceedingly rare
  • Incidence/Prevalence of Pulmonary Involvement: pulmonary involvement by metastatic calcification is common (although is usually asymptomatic and undetectable by CXR)


Etiology of Metastatic Calcification

(metastatic calcification is due to calcium deposition of calcium in previously normal tissues)

  • Secondary Hyperparathyroidism in Chronic Renal Failure:
    • Age, duration of hemodialysis, and type of underlying renal disease do not predict which patients will develop metastatic calcification
    • Risk of metastatic calcification increases with calcium-phosphate product >70 mg/dl
  • Primary Hyperparathyroidism: rare etiology of metastatic pulmonary calcification
  • Post-Liver Transplant:
  • Other Hypercalcemic States:
    • Milk-Alkali Syndrome:
    • Vitamin D Intoxication:
    • Rickets:
    • Collagen Vascular Disease:
    • Sarcoidosis:
    • Hypercalcemia of Malignancy (multiple myeloma, etc):

Etiology of Dystrophic Calcification

(dystrophic calcification is due to calcium deposition of calcium in previously damaged tissues)

  • Prior Granulomatous Infection (TB, Histo, and Sarcoid)
  • Prior Other Infection (Varicella, PCP)
  • Pneumoconiosis (Silicosis, Coal Worker’s Pneumoconiosis):


  • Metastatic calcification may also affect other visceral organs
  • Calciphylaxis: mechanism by which soft tissues respond to a variety of chemical sensitizers, leading to calcium deposition
  • ”Sensitizing”Factors:
    • Elevated PTH:
    • Calcium-Phsophate Product >70:
    • Vitamin D:
  • ”Challenging” Factors:
    • Immunosuppressants:
    • Corticosteroids:
    • Coumadin:
  • Pathogenesis of Skin Lesions: deposition of calcium salts (hydroxyapatite) in superficial arterioles -> fibroblast proliferation -> endovascular fibrosis
  • Calcium Salts Tend to Precipitate in Alkaline Conditions: deposition is predisposed in relatively alkaline conditions of the apical lungs (pH is near 7.5 in lung apices, due to higher V/Q ratios and lower CO2 concentration), stomach, kidneys, soft tissues, and skin
    • Intermittent alkalosis that occurs following hemodialysis may be a precipitating factor
  • Sites of Pulmonary Calcium Deposition:
    • Alveolar Septa: primary site of deposition
      • Septal thickening and fibrosis
    • Pulmonary Arterial Walls:
    • Bronchial Walls:


  • Linear or granular calcific deposits in alveolar septal walls (and pulmonary vessels and bronchi) with fibrosis


  • ABG: hypoxemia
  • PFT’s: abnormal in 90% of cases of metastatic calcification
    • Restriction:
    • Decreased DLCO:
  • CXR Patterns
    • Normal: in many cases
    • Calcified Patchy Pulmonary Infiltrates and/or Nodules (Up to 10 mm): only 15% of cases have abnormal CXR (as compared to autopsy findings)
      • Can be diffuse or localized
      • There is no correlation between radiographic involvement and clinical symptoms
      • May mimic pneumonia or pulmonary edema
      • Infiltrates are relatively stable over time, in contrast to those from infectious processes
    • Interstiital Infiltrates:
  • HRCT Patterns: HRCT is superior to CXR to diagnose calcifications -> patterns may coexist (not mutually exclusive)
    • Diffuse or Patchy Ground Glass Opacifications:
    • Dense Consolidation (Often in Lobar Distribution):
    • Multiple Diffuse or Localized Nodules:
    • Calcifications in Vessels of Chest Wall:
    • Calcification in Tracheobronchial Tree, Segmental Pulmonary Arteries, Myocardium:
  • Technetium-99m-Diphosphonate Bone Scan: highly specific
    • Allows detection of calcifications in all affected organs (including kidneys, stomach, and lungs)
    • Sensitivity: 24%
    • False-Positives: seen with lymphoma and pleural effusions
  • PTH: necessary to assess for hyperparathyroidism as the etiology
  • Echo: may reveal calcification of the conduction system and myocardium
  • Skin Bx: avoided, due to high probability of lesions not healing

Clinical Presentations

  • Asymptomatic: most cases are asymptomatic
  • Dyspnea/Dry Cough: some cases
  • Pulmonary Fibrosis/Respiratory Failure/Cor Pulmonale: occurs in very few cases
  • Skin Involvement
    • Painful, Violaceous Skin Lesions:
      • Usually bilateral and symmetric
      • May ulcerate and become necrotic/gangrenous


  • Best Treatment: prevention (maintaining normal levels of calcium and phosphate)
  • Decrease Dietary Calcium Intake: may be helpful
  • Treatment of Hyperparathyroidism:
    • Vitamin D Analogues: may be helpful to reduce PTH levels
    • Parathyroidectomy: may be necessary
      • 60% response rate
      • May result in marked improvement
      • Some patients may paradoxically worsen though
  • Taper Steroids/Immunosuppressants (as they have been implicated as sensitizers)
  • Renal Transplantation: may be effective in rare cases with significant respiratory compromise
    • However, some cases progress despite normal functioning renal transplant


  • Mortality Rate: 60%
  • The overall 1- and 5-year survival rates have recently been reported to be 45% and 35%, respectively
  • Death usually occurs due to sepsis


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