Association of IgG N-Glycans With Adverse Outcomes in CKD

Butz E, Bach MI, Kotsis F, Steinbrenner I, Štambuk T, Gudelj I, Trbojević BR, Pribić T, Mijakovac A, Nadal J, Eckardt KU, Lauc G, Köttgen A, Sekula P, Schultheiss UT (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Kidney International Reports Elsevier

Book Volume: 11

Article Number: 106615

Journal Issue: 8

DOI: 10.1016/j.ekir.2026.106615

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 (KF) within the German CKD (GCKD) study. Methods: IgG N-glycan peaks were measured using ultrahigh-performance liquid chromatography in 4782 GCKD participants (estimated glomerular filtration rate [eGFR]: 30–60 ml/min per 1.73 m2 or overt albuminuria). We assessed associations with baseline kidney function, 6.5-year mortality, and KF using linear and Cox regression. We used bidirectional Mendelian randomization (MR) to explore causal relationships. Results: The cohort comprised 4782 participants (mean age: 60 years, 40% women) with a median eGFR of 46 ml/min per 1.73 m2, and autoimmune kidney disease in 22%. Higher agalactosylated IgG was associated with lower eGFR (−4%/SD; 97.9% confidence interval [CI]: −6% to −3%) and higher mortality (hazard ratio [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 urinary albumin-to-creatine ratio [UACR] and KF varied by age, sex, and autoimmune status. Core fucosylation and bisecting N-acetylglucosamine (GlcNAc) 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 KF in CKD. These findings identify IgG N-glycans as potential immunologic biomarkers for CKD. Further validation is required to confirm causal relevance.

Authors with CRIS profile

Kai-Uwe Eckardt Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Albert-Ludwigs-Universität Freiburg DE Germany (DE) Genos Glycoscience Research Laboratory HR Croatia (HR) Universitätsklinikum Bonn DE Germany (DE)

How to cite

APA:

Butz, E., Bach, M.I., Kotsis, F., Steinbrenner, I., Štambuk, T., Gudelj, I.,... Schultheiss, U.T. (2026). Association of IgG N-Glycans With Adverse Outcomes in CKD. Kidney International Reports, 11(8). https://doi.org/10.1016/j.ekir.2026.106615

MLA:

Butz, Elena, et al. "Association of IgG N-Glycans With Adverse Outcomes in CKD." Kidney International Reports 11.8 (2026).

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