Histopathology of MPGN and C3 glomerulopathies

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Membranoproliferative glomerulonephritis (MPGN) is defined by glomerular injury with capillary wall thickening and mesangial expansion.
• Historically classified by electron microscopy findings, MPGN is now recognized as often involving complement component C3 deposition due to alternative pathway dysregulation.
• These C3 deposition cases are now termed C3 glomerulopathies, encompassing dense deposit disease and C3 glomerulonephritis.

Purpose of the Study:

• To clarify the evolving classification of MPGN.
• To highlight the significance of C3 deposition in glomerular diseases.
• To emphasize the diagnostic utility of identifying dominant C3 in identifying patients needing complement pathway investigation.

Main Methods:

• Review of historical and current classifications of MPGN.
• Electron microscopy findings in MPGN and C3 glomerulopathies.
• Identification of genetic mutations and autoantibodies associated with C3 deposition.

Main Results:

• Many cases previously diagnosed as MPGN are now classified as C3 glomerulopathies.
• C3 glomerulopathies result from abnormal alternative pathway of complement activation.
• Genetic mutations or autoantibodies are identified in a significant number of C3 deposition cases.
• Morphological diagnosis of 'glomerulonephritis with dominant C3' aids in identifying patients requiring complement pathway investigation.

Conclusions:

• The diagnosis of idiopathic MPGN is now rare.
• Understanding C3 glomerulopathies has refined the classification of glomerular diseases.
• Identifying the underlying cause, often complement-related, is crucial for patient management.