Association of IgG N-Glycans with Adverse Outcomes in Chronic Kidney Disease

Abstract Introduction IgG N-glycosylation modulates inflammation and may influence chronic kidney disease (CKD). We investigated associations between IgG N-glycan patterns, kidney function, mortality and kidney failure within the German CKD (GCKD) study. Methods IgG N-glycan peaks were measured via ultra-high-performance liquid chromatography in 4,782 GCKD participants (eGFR 30–60 mL/min/1.73 m² or overt albuminuria). We assessed associations with baseline kidney function, 6.5-year mortality, and kidney failure using linear and Cox regression. Bidirectional Mendelian randomization (MR) explored causal relationships. Results The cohort comprised 4,782 participants (mean age 60 years, 40% women) with a median eGFR of 46 mL/min/1.73 m² and autoimmune kidney disease in 22%. Higher agalactosylated IgG was associated with lower eGFR (−4% per SD; 97.9% CI −6% to −3%) and higher mortality (HR 1.39; 97.9% CI 1.19–1.62). Conversely, higher digalactosylated and sialylated IgG were associated with higher eGFR (+5%) and lower mortality (HR 0.68 and 0.80, respectively). Associations with UACR and kidney failure varied by age, sex, and autoimmune status. Core fucosylation and bisecting N-acetylglucosamine showed weaker associations, primarily with UACR. MR suggested bidirectional causal relationships between eGFR and specific N-glycan traits. Conclusion IgG N-glycan patterns reflect inflammatory aging and associate with kidney function, mortality, and kidney failure in CKD. These findings identify IgG N-glycans as potential immunologic biomarkers for CKD, though further validation is required to confirm causal relevance.