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Cryoglobulins and the Kidney M.J. Mihatsch, H.
Hopfer and F. Gudat Institute for Pathology Basel
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Laboratory diagnostic

• Do everything at 39-40 C
• Blood sample tube must be preheated
• Sample collection
• Transportation to the lab
• Centrifugation
• Clotting and separation of the serum
• Then serum is cooled to 4 C for 7 days

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Cryo-thrombi in CLL
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Skin lesions purpura and vasculitis

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Type II Renal manifestation

• Highly variable!
• Nephrosis
• Nephritis
• Proteinuria and hematuria
• Proteinuria or hematuria
• Hypertension
• Clinical course
• exacerbation-remission again and again

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Pathology Diagnostic features

• LM
• Membranoproliferative GN
• Many monocytes (with protein droplets)
• Protein thrombi
• Vasculitis
• IF
• Protein thrombi positive for Ig M gt Ig G
• Predominance of kappa gt lambda
• EM
• Organized deposits
• Clinical history
• Mixed cryglobulins

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Pathology

• Typical morphological features
• Three different patterns
• Vasculitis

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Typical morphological features
Diffuse massive glomerular hypercellularity
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Typical morphological features
Predominance of monocytes
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Typical morphological features
Protein thrombi
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Typical morphological features
Monocytes with protein droplets
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Typical morphological features
Organized deposits
Cryoprecipitate
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Immunoglobulins and Complement Factors
Prevalence
Severity
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Diagnosis
The diagnosis of Cryoglobulinemic GN should
only be made when organized deposits are present.
In all other cases we prefer the diagnosis GN
suggestive of cryoglobulinemic GN The clinical
information no cryoglobulins found is no
argument against the diagnosis of Cryo-GN For
many hospitals the technique for the
identifications of cryos is too complicated.
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Pathology

• Typical morphological features
• Three different patterns
• Vasculitis

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Different Patterns of Glomerulonephritis in
Mixed Cryoglobulinemia
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Pattern I
Thrombi and many monocytes
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Pattern I
Protein thrombus
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Pattern I
Massive monocyte accumulation
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Pattern I
Monocytes with protein droplets, thrombus and
subendothelail deposit
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Pattern I
Thrombi, monocytes and subendothelial deposits
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Distribution of deposits and other morphological
features (n25)
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Results of immunohistology
10 cases
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Immunohistochemistry
Ig M thrombi
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Immunohistochemistry
C3c often negative
Ig G thrombi less strong
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Diagnosis Cryoglobulinemic GN endocapillary
type early stage of mp GN
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Different Patterns of Glomerulonephritis in
Mixed Cryoglobulinemia
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Pattern II
Polynuclear leukocytes
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Pattern II
Mesangial interposition
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Pattern II
Massive mesangial proliferation
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Immunohistochemistry
IgG

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Results of immunohistology
20 cases
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Diagnosis Cryoglobulinemic GN Membranoprolifera
tive type
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Different Patterns of Glomerulonephritis in
Mixed Cryoglobulinemia
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Pattern III
Mesangial matrix increase, less mesangial
proliferation
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Pattern III
Mesangial matrix, less conspicuous mesangial
interposition
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Pattern III
Less prominent mesangial interposition
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Pattern III
Condensation of mesangial interposition and
matrix increase
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Pattern III
Progressive mesangial matrix increase
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Pattern III
Subendothelial deposits with signs of dissolution
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Pattern III
Advanced deposit dissolution and mesangial
interposition
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Pattern III
Advanced deposit dissolution
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Diagnosis Cryoglobulinemic GN Membranoprolifera
tive type Or Mesangioproliferative type Or
Minor glomerular abnormalities
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Pathology

• Typical morphological features
• Three different patterns
• Vascular lesions and vasculitis
• (15 or more)

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Vascular lesions
PTC and Vasa recta with protein thrombi
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Vascular lesions
Vascular protein thrombi
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Vasculitis
Late necrotizing vasculitis and protein thrombus
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Vasculitis
Proliferative endovasculitis
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Vasculitis
Necrotizing vasculitis similar to PAN
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Aetiology and pathogenesis e.g. in hepatitis C
80-90
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Pathogenesis
B Lymphocyt
Immune response
HCV
IgG
HCV/IgG
other GN?
DAmico G Kidney Int 54650,1998
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Pathogenesis
Infection
HCV
IgG
IgM
HCV/IgG
other GN?
DAmico G Kidney Int 54650,1998
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Pathogenesis
HCV
IgG
IgM
IgG/IgM
HCV/IgG
Immune complex deposition
other GN?
Cryoglobulinemic GN
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