Supplementary Material for: Punctate Podocyte IgG Staining Does Not Differentiate Primary from Secondary Minimal Change Disease

Introduction: Punctate IgG staining of podocytes ('dusting') identified by immunofluorescence recently has been described in a subset of minimal change disease (MCD), possibly correlating with anti-nephrin or other autoantibodies. Whether dusting is associated with other clinicopathologic features of MCD remains unclear, but identification of these associations could provide insight into MCD mechanisms, prognosis, and therapeutic strategies. Methods: Cases with a diagnosis of MCD over 8.5 years at one institution were retrospectively reviewed, including re-examination of IgG immunofluorescence and electron microscopy when necessary. Demographic, clinical, and ultrastructural feature data were collected. Cases were divided into presumed primary and secondary MCD based on clinical associations and they were assessed for dusting frequency. Results: 371 cases were included, of which 73% were primary MCD and 16.4% were pediatric. Dusting frequency among MCD etiologies ranged from 45-63% and did not differ between children and adults, or in primary vs any secondary MCD association. Dusting was positively correlated with the degree of podocyte foot process effacement (p<0.005) and actin cytoskeletal condensation (p = 0.001). Otherwise, dusting was not associated with other ultrastructural features of proteinuric kidney disease or with podocyte ballooning clusters. Conclusion: Podocyte IgG dusting was not specific for any one etiologic trigger of MCD or age category. This suggests that autoantibodies may induce MCD irrespective of a primary (idiopathic) versus a presumed secondary cause, which may alter the diagnostic and therapeutic approach. Additionally, podocyte ultrastructural features associated with dusting may reflect mechanisms of autoantibody-induced injury, or may represent a feature of disease severity and/or temporal progression.