Cryoglobulinemic Glomerulonephritis

The following text taken from: Fogo AB, et al. Am J Kidney Dis. 2016;67(2):e5-7. [PubMed link] [Full text link]: Cryoglobulinemic glomerulonephritis (GN) is caused by intracapillary, subendothelial, and mesangial cryoglobulin deposits, giving a membranoproliferative pattern of injury. Patients have nephritic/nephrotic syndrome with various levels of kidney function. Purpura and arthralgia occur in about one-third, with vasculitis affecting skin and kidneys less commonly. Abnormal serologic studies include low C4 in three-quarters and low C3 in half. All 3 types of cryoglobulins, including those due to both monoclonal and polyclonal immunoglobulins, can cause cryoglobulinemic GN, although most commonly it occurs in settings of type II (“mixed”) cryoglobulinemia secondary to hepatitis C virus infection. Most patients with type II or III cryoglobulins have a positive rheumatoid factor.

Light microscopy: There is mesangial proliferation and often diffuse and global endocapillary hypercellularity. Eosinophilic refractile intracapillary “cryo-plugs” that are strongly periodic acid–Schiff (PAS) positive are due to the IgM component of these deposits. The acute phase has frequent neutrophils, with increased monocyte/macrophages in both acute and chronic stages. Arterioles and small arteries may show leukocytoclastic vasculitis, sometimes with cryoglobulin deposits. Crescents may be present.

Immunofluorescence microscopy: Mesangial and chunky irregular capillary wall deposits often appear sausage-shaped due to molding under the glomerular basement membrane (GBM). There is prominent IgM and C3, often with clonal bias of κ light chain versus λ, with similar or lesser amounts of IgG or C1q. Cryo-plugs typically show strong IgM and clonal κ or λ staining, and may show similar staining for IgG in type II and III cryoglobulinemia.

Electron microscopy: Mesangial and subendothelial deposits, often with interposed cells and double contours due to new GBM formation beneath subendothelial deposits are common. Intracapillary deposits, extensive foot process effacement, and endocapillary hypercellularity also occur. Deposits may show vague, short fibrillary substructure and be organized as tactoids similar to fibrin. Monoclonal cryoglobulin deposits may be microtubular and highly organized (Fogo AB, et al. AJKD Atlas of Renal Pathology: Cryoglobulinemic Glomerulonephritis. Am J Kidney Dis. 2016;67(2):e5-7. [PubMed link] [Full text link]).

In our case, a mediatinal B cell lymphoma was documented, then, "lymphoma-associated cryoglobulinemic GN" was the final diagnosis in the kidney biopsy.

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Fogo AB, Lusco MA, Najafian B, Alpers CE. AJKD Atlas of Renal Pathology: Cryoglobulinemic Glomerulonephritis. Am J Kidney Dis. 2016;67(2):e5-7. [PubMed link] [Full text link].