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Kidney Week

Abstract: TH-PO1001

Kidney Transplantation and Donor Age Affect Recipient Biological Age and Remodel Immunoglobulin G Glycosylation and Proteoform Profiles

Session Information

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Forte, Eleonora, University of Illinois Chicago, Chicago, Illinois, United States
  • Minicucci, Carlo, University of Illinois Chicago, Chicago, Illinois, United States
  • Gessaroli, Elisa, University of Illinois Chicago, Chicago, Illinois, United States
  • Claeys, Jane, University of Illinois Chicago, Chicago, Illinois, United States
  • Dwaraka, Varun B., TruDiagnostic LLC, Lexington, Kentucky, United States
  • Giron, Leila, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Sanchez Puente, Aniel, Northwestern University, Evanston, Illinois, United States
  • Pla, Indira, Northwestern University, Evanston, Illinois, United States
  • Zhang, Lily, University of Illinois Chicago, Chicago, Illinois, United States
  • Ribeiro Grossi Araújo, Lourenço, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
  • Priscilla, Shamulailatpam, University of Illinois Chicago, Chicago, Illinois, United States
  • Doshi, Nidhi Kajal, University of Illinois Chicago, Chicago, Illinois, United States
  • Eshac, Fares, University of Illinois Chicago, Chicago, Illinois, United States
  • Donini, Sara, University of Illinois Chicago, Chicago, Illinois, United States
  • Abuzeineh, Mohammad, University of Illinois Chicago, Chicago, Illinois, United States
  • Hollas, Michael, Northwestern University, Evanston, Illinois, United States
  • Le, Nhat, Northwestern University, Evanston, Illinois, United States
  • Smith, Ryan, TruDiagnostic LLC, Lexington, Kentucky, United States
  • Abdel-Mohsen, Mohamed, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kelleher, Neil, Northwestern University, Evanston, Illinois, United States
  • Benedetti, Enrico, University of Illinois Chicago, Chicago, Illinois, United States
  • Valdepenas, Benito, University of Illinois Chicago, Chicago, Illinois, United States
  • Vaughan, Douglas E., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Gallon, Lorenzo G., University of Illinois Chicago, Chicago, Illinois, United States
Background

Patients with chronic kidney disease exhibit accelerated biological aging (BA); however, the impact of kidney transplantation (KT), the optimal treatment for end-stage kidney disease, and donor age on BA and serum components remains limited. Here, we investigated whether KT and donor age affect BA and their impact on immunoglobulin G (IgG) glycan and proteoform profiles to gain more insights into KT and aging.

Methods

This study involved 40 KT recipients (>60 years old), stratified by donor age (≤40 and ≥60 years). DNA, serum samples, and clinical data, including electrocardiogram (ECG) traces, were collected pre- and post-KT (>8 months). BA was assessed by ECG-Age algorithms and epigenetic clocks. Differences between pre- and post-KT Age Acceleration (ΔAA), calculated as BA-chronological age (CA), were used to evaluate the impact of KT on BA. Epigenetic Immune Acceleration (IAA) was calculated as the residual from a linear regression of BA on CA, regressing out the effects of immune cells, affected by KT and immunosuppression. IgGs were purified from serum, and N-glycans were released, labeled, and analyzed by capillary electrophoresis. Serum proteoforms were analyzed by top-down proteomics (Individual ion mass-spectrometry).

Results

Both cardiovascular and epigenetic assessments suggested a trend toward rejuvenation in recipients of younger donor kidneys after KT. ECG-Age estimated a ΔAA of −3.7 years, whereas epigenetic clocks, including OMICmAge and PhenoAge, confirmed this trend, showing a significant decrease in IAA. KT was also associated with a significant increase in anti-inflammatory galactosylated and sialylated IgG glycans and a decrease in pro-inflammatory agalactosylated and hypo-sialylated traits, suggesting a shift toward a less inflammatory, biologically younger profile. Finally, proteoform analysis identified profiles associated with KT and donor age, including several novel proteoforms derived from proteins with known roles in aging, such as Apolipoprotein A1 and Leptin.

Conclusion

This study indicates that KT influences biological aging trajectories by reducing cardiovascular and epigenetic AA and suggests a key role of donor age in post-KT rejuvenation. Additionally, KT was associated with IgG glycan reorganization and specific proteoform signatures. Independent, larger cohorts are required to validate these findings.