DEMOGRAPHIC AND CLINICAL PROFILES OF C3 GLOMERULOPATHY AND IGA NEPHROPATHY IN BRAZIL: A REAL‑WORLD COHORT FROM 2018-2025

Glomerulonephritides are heterogeneous disorders with distinct epidemiology, pathophysiology, and outcomes. C3 glomerulopathy (C3G) is an ultrarare complement-mediated disease, whereas IgA nephropathy (IgAN)—the most common primary glomerulonephritis—is immune-mediated, both with notable risks of end-stage renal disease and post-transplant recurrence. In Brazil, limited evidence on C3G and IgAN highlights the need to characterize patients to guide context-specific care. This study aims to describe the demographic and clinical profiles of patients diagnosed with C3G or IgAN in Brazil. 

Retrospective, observational study conducted using secondary data supplied by iHealth Group, comprising routinely collected, structured electronic health records from 26 healthcare providers across Brazil. Data were standardized using Smart Health Connect (SHC), a Natural Language Processing (NLP) tool that employs Portuguese clinical NER (RoBERTa-based) to identify and classify clinical entities (e.g., diseases, medications, procedures) and an Assertion Detection model to determine contextual status (present, absent, historical, possible). IgAN and C3G cases were identified through automated detection of diagnostic key terms, exploration of disease-related entities, contextual filtering by assertion status, and expert validation by a nephrologist. Patients with IgAN or C3G diagnosed between January 2018 and September 2025 were included. Renal outcomes were analyzed as time-to-event from diagnosis (t0).

A total of 2.228.641 clinical entities were analyzed for C3G (22%) and IgAN (78%). The cohort comprised 332 patients with confirmed IgAN and 25 with confirmed C3G, with similar mean age at diagnosis (IgAN 42.3 years; C3G 43.3 years) and male predominance (IgAN 54.5%; C3G 60.0%). Most patients lived in the Southeast, notably Minas Gerais (IgAN 54.8%; C3G 80.0%). Proteinuria was markedly elevated in both cohorts: IgAN showed a median UPCR of 2.628 mg/g [IQR 2.218–4.371], with 94.3% in KDIGO A3, whereas C3G had a median UPCR of 651 mg/g [IQR 184–824], with 67.1% in A3. Renal outcomes reflected high baseline severity and kidney functional injury. In IgAN, eGFR <30 mL/min/1.73 m² occurred in 25.0% of patients, with a median time of 0 days [IQR 0–44]; dialysis occurred in 21.1%, with 0.5 days [IQR 0–12]; and transplantation occurred in 10.5%, with 14 days [IQR 0–210]. In contrast, C3G had higher event rates: eGFR <30 occurred in 84.0%, with 0 days [IQR 0–0]; dialysis in 76.0%, with 1 day [IQR 0–12]; and transplantation in 36.0%, with 7 days [IQR 0–194]. Management of comorbidities and complications were nearly universal across cohorts (98.7% in IgAN and 100.0% in C3G); IgAN commonly received diuretics (48.7%), systemic corticosteroids (46.5%), and RAAS inhibitors (62.5%), while C3G relied more heavily on corticosteroids (75.0%), diuretics (75.0%), and RAAS inhibitors (62.5%). Targeted therapies included eculizumab in 4.2% of C3G and Nefecon in 2.5% of IgAN patients.

In a Brazilian real-world cohort, IgAN and C3G patients were often identified with KDIGO A3 proteinuria, indicating high risk at presentation. Therapeutic heterogeneity reflects broad supportive practices, with greater corticosteroid use in C3G. Future studies using standardized histologic definitions are needed to estimate disease progression and compare therapies in Brazil.