Cryoglubulins & The Kidney

In short – CG

CGs are immunoglobulins and complement components that precipitate upon refrigeration of plasma.

Brouet’s Classification of CG



Everyone in general has a low level of CG; this reflects ongoing background clearance of endogenous immune complexes with RF activity. Abnormally raised levels of  CG would mean:

  1. Chronic immune stimulation or lymphoproliferative disease leading to higher concentrations of mono, oligo or polyclonal CGs.
  2. Immune complex formation between the CGs and their target antigens
  3. Insufficient or defective clearing of CGs

Mixed CGs

  • Deposition of Ab-Ag complexes in capillaries and small arterioles along the vessel wall with cryoproteins within the vessel lumen
  • Skin biopsy shows a leukocytoclastic vasculitis
  • C4 is normally low (but not always) reflecting complement consumption via the classical pathway of the complement cascade

CGs and the Kidney

  • >80% show MPGN with thickening of the GBM and cellular proliferation and +++macrophages
  • Light microscopy : capillary microthrombi
  • Immunofluoroscence : Diffuse IgM deposition in the capillary loops
  • EM : Subendothelial deposits in the mesangium with characteristics ‘finger print’ appearance. CGs are too big to pass through the GBM hence uncommon to appear in the sub epithelial space
  • Presentation can be:
    • Haematuria +/- renal insufficiency
    • Nephrotic syndrome
    • Acute nephritis
    • AKI



Source : The Lancet, 2012