Kidney Week

Abstract: TH-PO1041

Association of IgG Glycosylation with Kidney Markers and CKD Progression

Session Information

• CKD: Epidemiology, Risk Factors, and Prevention - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Schultheiss, Ulla T., Universitatsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany

Ulla T. Schultheiss, MD

• Butz, Elena, Universitatsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany

Elena Butz, MSc

• Gudelj, Ivan, University of Rijeka, Faculty of Biotechnology and Drug Development, Rijeka, Croatia

Ivan Gudelj, PharmD, PhD

• Radovani, Barbara, University of Rijeka, Faculty of Biotechnology and Drug Development, Rijeka, Croatia

Barbara Radovani, PhD

• Kottgen, Anna, Universitatsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany

Anna Kottgen, MD, MPH

• Sekula, Peggy, Universitatsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany

Peggy Sekula, PhD

Group or Team Name

• GCKD Study Investigators.

Background

Glycosylation profiles of immunoglobulin G (IgG) has been associated with kidney function and chronic kidney disease (CKD) in the general population but has not been explored in CKD cohorts. Glycans, like galactose, modulate immune responses and may impact kidney diseases. Our aim was to identify glycosylation patterns associated with kidney function markers and CKD progression to kidney failure (KF) and mortality among CKD patients.

Methods

Plasma samples from 4819 German CKD (GCKD) study participants were analyzed for 24 IgG glycans. This abstract focuses on 12 traits derived from these measurements, related to either complete or partial glycosylation patterns. Linear and Cox regression models, adjusted for confounders, evaluated associations with eGFR, UACR, KF, and mortality. A significance threshold of p=0.0021 (0.05/24) was used.

Results

The study included 460 participants reaching KF and 607 died during 6.5-years follow-up. Mean age was 60.1 years, with 39.8% females, median UACR of 50.8 mg/g, and median eGFR of 49.4 mL/min/1.73m². Most glycosylation patterns showed significant results, none were associated with KF, e.g. an increase of one standard deviation total galactosylated IgG (gal_total) was significantly associated with a 0.045 mL/min/1.73m² increase in eGFR and a 0.11 mg/g decrease in UACR. Higher levels of gal_total were linked to a lower risk of mortality (Hazard Ratio 0.72), indicating a protective effect. Similar protective effects were observed for s1, s1_no_bis, g2, and g1, while harmful associations were found for s1_g2 and g0.

Conclusion

Our study shows that certain patterns of glycosylation in IgG N-glycans are associated with kidney function and mortality. Galactosylation and specific sialylation patterns are linked to better kidney function and lower mortality, while agalactosylation and specific ratios of sialylation are associated with poorer kidney function and higher mortality. Ongoing analyses will further explore these associations.

Funding

• Government Support – Non-U.S.