Primary Membranoproliferative Glomerulonephritis: Natural History, Pathogenesis, and Treatment

Authors

Edward J. Filippone, Thomas Jefferson UniversityFollow
John L. Farber, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

2-13-2026

Comments

This article is the author's final published version in Frontiers in Nephrology, Volume 6, 2026, Article number 1747678.

The published version is available at https://doi.org/10.3389/fneph.2026.1747678. Copyright © 2026 Filippone and Farber.

Abstract

Primary membranoproliferative glomerulonephritis (MPGN) is an ultrarare disease characterized by immunofluorescence microscopy as either immune-complex mediated (IC-MPGN) or C3 glomerulopathy (C3), the latter subdivided by electron microscopy to C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both IC-MPGN and C3G typically have obvious C3 staining differentiating them from other causes of MPGN histology. Secondary causes must be excluded, including infections, autoimmune disease, and neoplasia. Clinical presentations are variable, including urinary sediment abnormalities, nephrotic syndrome, or a rapidly progressive course. The prognosis is unfavorable with about 50% reaching kidney failure by 10 years. Recurrence following transplantation is frequent, and allograft survival is shortened. The pathogenesis involves dysregulation of the alternate pathway (AP) of complement. Possibly 20% of patients harbor pathogenic mutations in AP proteins or their regulators, and up to 80% have autoantibodies impairing normal regulation. Paraproteins are found in 20 - 40% of otherwise primary MPGN, either directly detectable on biopsy (IC-MPGN) or as dysregulators of the AP. Therapy of MPGN begins with supportive care as for all glomerulopathies. Paraproteins require clone-directed therapy. When immunosuppression is considered, complement inhibition should be first line. Two agents are now FDA approved for C3G, the oral Factor B inhibitor iptacopan and the subcutaneous C3-inhibitor pegcetacoplan, the latter also approved for IC-MPGN. If complement inhibition is unavailable, MMF/steroids may be considered. Following transplantation, protocol biopsies are needed to detect early recurrence with the intent of complement inhibition.

Recommended Citation

Filippone, Edward J. and Farber, John L., "Primary Membranoproliferative Glomerulonephritis: Natural History, Pathogenesis, and Treatment" (2026). Division of Nephrology Faculty Papers. Paper 12.
https://jdc.jefferson.edu/nephrologyfp/12

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English