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MPGN Reclassification C3G IF-Based — ESENeph MCQ

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ModerateGlomerulonephritisMPGN Reclassification C3G IF-BasedESENeph

A 45-year-old man with primary membranoproliferative GN (MPGN) is being investigated. His complement studies show: low C3, normal C4, positive C3 nephritic factor (C3NeF), and no monoclonal protein. IF shows dominant C3 with trace immunoglobulins. What is the reclassified diagnosis?

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Correct answer: E — C3 glomerulopathy (C3 glomerulonephritis subtype) – the dominant C3 with minimal Ig, low C3, normal C4, and C3NeF indicate alternative complement pathway dysregulation; MPGN is now reclassified based on IF: Ig-positive MPGN vs C3 glomerulopathy

Explanation lettering: C = shown as A · E = shown as B · B = shown as C · A = shown as E

The modern classification of MPGN is based on immunofluorescence rather than light microscopy pattern: (1) Ig-positive MPGN: significant immunoglobulin deposits – indicates immune complex-mediated disease (investigate infections, autoimmune, monoclonal gammopathy); (2) C3 glomerulopathy (C3G): dominant C3 with absent/trace Ig – indicates alternative complement pathway dysregulation. C3G is further subdivided into C3 glomerulonephritis and dense deposit disease (by EM). This reclassification changed management: C3G requires complement investigation (C3NeF, factor H/I levels, genetic testing) and may respond to complement-targeted therapy.

Reference: KDIGO 2021 – GN; Sethi and Fervenza 2012 – MPGN Reclassification