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Kidney non-tumor

Associated with systemic conditions


Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 15 September 2012, last major update September 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.


● 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’s 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

● 7 year old boy with glomerular rhomboid inclusions (Am J Kidney Dis 2009;53:866)
● 55 year old man with Hepatitis C (J Med Case Rep 2009;3:91.)
● 58 year old woman with ultrastructural diagnosis of cryoglobulinemic glomerulonephritis (Arch Pathol Lab Med 1981;105:474)
● 60 year old man with Hepatitis B virus associated type II cryoglobulinemia and severe multisystem disease, treated with Rituximab (J Med Case Rep 2012;6:39)
● 81 year old man with essential type II cryoglobulinemia unrelated to Hepatitis virus (Geriatr Gerontol Int 2009;9:92)


● Double filtration plasmapheresis; cryofiltration (Ther Apher Dial 2012;16:91)
● Possibly interferon for Hepatitis C related cases (Ren Fail 2009;31:149)
● Possibly Rituximab in nonviral patients age 70 years or less (Arthritis Care Res (Hoboken) 2010;62:1787, Autoimmun Rev 2011;11:48)

Micro 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

Micro images

Cryoglobulin-related glomerulonephritis-various images

With hepatitis C associated cryoglobulinemia

Chronic lymphocytic leukemia and cryoglobulinemic glomerulonephritis


● Immunoglobulins, strong C3; also C1q and C4

Immunofluorescence images

Globular accumulations of cryoglobulin in the capillary lumens

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

Various images

Differential diagnosis

Fibrillary glomerulonephritis: 15-30 nm fibrils
Immunotactoid glomerulopathy

End of Kidney non-tumor > Associated with systemic conditions > Cryoglobulinemia

Ref Updated: 7/24/12

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