A nephritic puzzle: C3-dominant glomerulonephritis as a sentinel of hidden autoinflammatory disease

Ryan C Ward; Polly Ferguson; Prerna Rastogi; Carla Nester; Hua Sun

doi:10.1007/s00467-026-07220-x

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A nephritic puzzle: C3-dominant glomerulonephritis as a sentinel of hidden autoinflammatory disease

Journal article

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A nephritic puzzle: C3-dominant glomerulonephritis as a sentinel of hidden autoinflammatory disease

Ryan C Ward, Polly Ferguson, Prerna Rastogi, Carla Nester and Hua Sun

Pediatric nephrology (Berlin, West)

02/20/2026

DOI: 10.1007/s00467-026-07220-x

PMID: 41718733

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Abstract

Membranoproliferative glomerulonephritis (MPGN) is among the most challenging glomerulonephritides to diagnose and manage, given its clinico-immunopathologic heterogeneity. Although recent advances have introduced new therapies for complement-mediated and immune-complex MPGN, a substantial subset of cases remains poorly understood and lacks effective treatment. We report a pediatric case of biopsy-confirmed C3-dominant MPGN without evidence of complement dysregulation, with disease flares triggered by febrile episodes. Genetic testing identified underlying hyper-IgD syndrome (HIDS), a rare autoinflammatory disorder characterized by recurrent fevers and immune dysregulation. The patient's MPGN was refractory to conventional immunosuppressive therapy but achieved remission with IL-1β blockade that targets HIDS. This case highlights the importance of considering alternative etiologies-including autoinflammatory diseases-in patients with MPGN when complement dysregulation is not evident.

HIDS

Complement pathway

MPGN

Details

Title: Subtitle: A nephritic puzzle: C3-dominant glomerulonephritis as a sentinel of hidden autoinflammatory disease
Creators: Ryan C Ward - University of Iowa
Polly Ferguson - University of Iowa
Prerna Rastogi - University of Iowa
Carla Nester - University of Iowa
Hua Sun - University of Iowa
Resource Type: Journal article
Publication Details: Pediatric nephrology (Berlin, West)
DOI: 10.1007/s00467-026-07220-x
PMID: 41718733
NLM abbreviation: Pediatr Nephrol
ISSN: 0931-041X
eISSN: 1432-198X
Publisher: Springer Nature
Grant note: 1R01DK136563 / NIDDK NIH HHS
Language: English
Electronic publication date: 02/20/2026
Academic Unit: Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Pathology; Rheumatology, Allergy, and Immunology; Internal Medicine
Record Identifier: 9985139301902771

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