Membranoproliferative Glomerulonephritis Pattern of Injury

Abstract

Membranoproliferative glomerulonephritis (MPGN) is no longer a disease but a pattern of injury in various diseases. Characterized by electron-dense deposits, mesangial proliferation, and duplication of the glomerular basement membrane, MPGN was previously classified by findings seen by electron microscopy. However, recognizing complement dysfunction in relation to cases with the MPGN pattern of injury substantially changed our view of its pathogenesis. A new classification, including immune complex-mediated and complement-mediated MPGN, has become preferable and has been adopted by international guidelines. Despite these advancements, accurate diagnosis of MPGN remains a clinical challenge, given the pathological and clinical similarities between immune complex-mediated and complement-mediated MPGN. Additional testing, such as molecular and genetic testing, is often necessary. Here, we will summarize our current understanding of the MPGN pattern of injury from a pathology perspective as an introductory article in the following chapters.

Keywords: Complements; Immune complex; Membranoproliferative glomerulonephritis.

Figure 1.

Membranoproliferative glomerulonephritis with immune complex deposition. (A) Periodic acid-Schiff (PAS) staining demonstrates mesangial (arrow) and endocapillary (arrowhead) proliferation. (B) Granular staining of IgG by immunofluorescence. (C) Subendothelial and mesangial deposits by electron microscopy. Courtesy of Dr. Neeraja Kambham, Professor of Pathology. Stanford University School of Medicine.

Figure 2.

Laboratory evaluation of MPGN. Adapted from KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. [Ref 5] HIV, human immunodeficiency virus; SLE, systemic lupus erythematous; AP50, complement alternate pathway 50%, CFB, complement factor B; CFH, complement factor H; CFHR1–5, complement factor H-related protein 1–5; CFI, complement factor I; CH50, complement hemolytic activity 50%; FB, factor B; FH, factor H; MAC, membrane attack complex.

Figure 3.

C3 glomerulonephritis. (A) GBM duplication, with “tram-tracking” appearance by silver staining (arrow). (B) Granular staining of C3 by immunofluorescence. (C) Significant subendothelial deposits shown by electron microscopy. Courtesy of Dr. Neeraja Kambham, Professor of Pathology. Stanford University School of Medicine.

Figure 4.

Dense deposit disease. (A) Positive C3 staining by immunofluorescence. (B) Classic lesion of linear-appearing and electron-dense deposits demonstrated by electron microscopy. Courtesy of Dr. Neeraja Kambham, Professor of Pathology. Stanford University School of Medicine.