Kidney nontumor / medical renal

Glomerular disease

Other primary glomerular disease


Last author update: 3 September 2012
Last staff update: 19 December 2023 (update in progress)

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PubMed Search: Cryoglobulinemia [title] kidney pathology

Nikhil Sangle, M.D.
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Cite this page: Sangle N. Cryoglobulinemia. website. Accessed February 22nd, 2024.
Definition / general
  • See also topic in Bone marrow neoplastic chapter
  • Usually systemic disease in which deposits of IgG or IgM immune complexes cause glomerulonephritis (focal, diffuse), cutaneous vasculitis (skin rash) and synovitis (arthritis)
  • Defined by presence of serum cryoglobulins, which are immunoglobulin complexes that precipitate at 4°C and become soluble again at 30°C
  • Type I: cryoglobulin is single monoclonal immunoglobulin class, usually due to myeloma, Waldenström macroglobulinemia or other lymphoma
  • Type II: mixture of 2+ immunoglobulins, one a monoclonal antibody against polyclonal IgG; usually IgG-IgM, in which IgM is monoclonal and has rheumatoid factor activity
  • Type III: both immunoglobulin components are usually polyclonal IgG and IgM
Clinical features
  • Symptoms of fatigue, purpura over lower extremities, arthralgias, hepatosplenomegaly, lymphadenopathy, Raynaud phenomenon, glomerulonephritis in 50% with proteinuria and hypertension, progressing to renal failure in 5%
  • Usually women ages 30+ years
  • Hepatitis C virus is major cause of mixed cryoglobulinemia
  • Renal disease unrelated to Hepatitis C is often related to primary Sjögren Syndrome (Medicine (Baltimore) 2009;88:341)
  • Cryoglobulinemia found in 83% of chronic hemodialysis patients, although not necessarily symptomatic (Ren Fail 2011;33:801)
  • Types II and III associated with B cell lymphoma, chronic infection, chronic liver disease, SLE and hepatitis C
Case reports
Microscopic (histologic) description
  • Expanded mesangium with thickened capillaries
  • Diffuse proliferative glomerulonephritis, often with membranoproliferative pattern
  • Also focal and segmental glomerulonephritis and less often crescentic or membranous glomerulonephritis
  • Acutely may produce wire loops or thrombi seen in lupus nephritis, vasculitis of interlobular arteries and afferent arterioles
Microscopic (histologic) images

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Cryoglobulin related glomerulonephritis

Immunofluorescence description
  • Immunoglobulins, strong C3; also C1q and C4
Electron microscopy description
  • Large amounts of subendothelial immune complex deposits; lesser amounts of subendothelial deposits
  • 50% have glomerular deposits with 25 - 35 nm microtubules forming bundles or arranged in fingerprint-like array
Electron microscopy images

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Various images

Differential diagnosis
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