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.
Ward et al. (Fri,) studied this question.