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. 2010 May;5(5):770-82.
doi: 10.2215/CJN.06760909. Epub 2010 Feb 25.

Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy

Sanjeev Sethi  1 , Ladan Zand, Nelson Leung, Richard J H Smith, Dragan Jevremonic, Sandra S Herrmann, Fernando C Fervenza
Affiliations

Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy

Sanjeev Sethi et al. Clin J Am Soc Nephrol. 2010 May.

Abstract

Background and objectives: Membranoproliferative glomerulonephritis (MPGN) is an immune complex-mediated glomerulonephritis characterized by subendothelial and mesangial deposition of immune complexes. Autoimmune diseases and chronic infections, such as hepatitis C, are commonly recognized causes of MPGN; however, monoclonal gammopathy is a less widely recognized cause of MPGN.

Design, setting, participants, & measurements: We reviewed all renal biopsies of MPGN in Mayo Clinic patients during a 6-year period to determine the association of monoclonal gammopathy with MPGN. Results were correlated with electrophoresis studies and bone marrow biopsies to clarify the relationship between MPGN and gammopathies.

Results: Of 126 patients with MPGN, 20 did not have workup for hepatitis B or C. Of the remaining 106 patients, 25 (23.5%) were positive for hepatitis B or C. Of the 81 hepatitis-negative patients, 13 were not evaluated for gammopathies. Of the remaining 68 patients, 28 (41.1%) had serum and/or urine electrophoresis studies positive for monoclonal gammopathy. Serum immunofixation electrophoresis was the most sensitive method for diagnosing monoclonal gammopathy. Renal biopsy showed a membranoproliferative pattern of injury; immunofluorescence microscopy was often instrumental in diagnosing the underlying gammopathy. On the basis of the bone marrow biopsy, monoclonal gammopathy of undetermined significance was the most common entity associated with MPGN. Other, less common causes included multiple myeloma, low-grade B cell lymphoma, and chronic lymphocytic leukemia.

Conclusions: Monoclonal gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal gammopathy.

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Figures

Figure 1.
Figure 1.
Summary of workup of patients with MPGN.
Figure 2.
Figure 2.
Representative light microscopy showing MPGN. (A) Hematoxylin- and eosin-stained section showing a hypercellular glomerulus with lobular accentuation of the glomerular tufts. (B) Periodic-acid Schiff–stained section showing mesangial expansion, endocapillary proliferation, and thickened glomerular basement membranes. (C) Silver stain showing cryoglobulins (arrow) in the lumen and immune deposits along the capillary walls. (D) Silver stain showing double contours (arrow) along the capillary wall. Magnifications: ×40 in A through C; ×60 in D.
Figure 3.
Figure 3.
Immunofluorescence microscopy. Each panel represents one case. (A) Granular capillary wall staining for IgM. (B) Negative staining for λ light chains. (C) Positive staining for κ light chains. (D) Mesangial staining for IgG. (E) Positive mesangial staining for κ light chains. (F) Negative staining for λ light chains. (G) Granular capillary wall staining for IgG. (H) Negative staining for κ light chains. (I) Positive staining for λ light chains. (J) C3 staining along capillary walls.
Figure 4.
Figure 4.
EM ultrastructural studies show subendothelial deposits (arrows), with new basement formation resulting in double contours. Magnifications: ×1850 in A; ×5800 in B.
Figure 5.
Figure 5.
Summary of plasma cell and lymphoproliferative disorders associated with MPGN.
See this image and copyright information in PMC

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