Novel Candidate Markers Characterizing Cellular Senescence in Aged Zero Hour Kidney Biopsies Predict Post Transplant Outcome
Department for Surgery, Medical University Innsbruck, Innsbruck, Austria
Division of Nephrology, Medical University Innsbruck, Innsbruck, Austria
Department for Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany
Meeting: 2013 American Transplant Congress
Abstract number: 257
Advanced donor age adversely affects allograft outcome following renal transplantation. Candidate genes involved in cell-cycle regulation and telomere shortening have been already described as markers for cellular senescence. However, there is still a lack of appropriate biomarkers for defining marginal organs in order to improve long-term outcome. To more comprehensively characterize senescence in the elderly donor organ, we first studied gene expression for selected candidate markers in a sample cohort consisting of 57 zero hour kidney biopsies derived from deceased donors (n=26, >55 yrs, 66.5±7.4 yrs and n=31, < 55 yrs, 41.35±8.4 yrs). Compared with younger donors, elderly donors revealed a significant de novo mRNA expression of candidate markers including immunoproteasome subunits (PSMB8,9,10; p<0.001 respectively), chemokines CCL19/21 (p<0.05), MHC class II transcript HLA-DRB (p<0.01) or the activating receptor NKG2D (p=0.0036). Next, we confirmed gene expression of candidate genes in a patient cohort consisting of 139 biopsy samples. Based on sample size, 3 groups were defined according to donor age: 0-30 yrs (group I, 21±4.9 yrs, n=30), 31-54 yrs (group II, 46.5±6.6 yrs, n=50) and >55 yrs (group III, 64.07±7 yrs, n=59). Whereas no differences were observed between group I and group II, aged kidneys (group III) revealed a significant gene expression of PSMB9 (p=0.0405), PSMB10 (p=0.0223), CCL19 (p=0.0318) compared with middle aged kidneys (group II). Strikingly, transcripts of the activating NK cell receptor NKG2D revealed the highest gene induction in group III versus group II and group I (p<0.001, respectively) indicating enhanced infiltration of NKG2D+ CD8+ T cells or NK cells in older kidneys. Linear restriction analysis revealed a strong correlation for pre-transplant NKG2D mRNA expression with serum creatinine levels at hospital discharge (p=0.0003), at 3 months (p=0.004) and at 6 months post transplantation (p=0.0031). Our results reveal novel candidate markers in aged renal allografts providing help in the assessment of organ quality and implicating the potential of pretreatment strategies.
To cite this abstract in AMA style:
Kotsch K, Guenther J, Hutter P, Schwelberger H, Biebl M, Schneeberger S, Öllinger R, Weissenbacher A, Neuwirt H, Mayer G, Stauch D, Pascher A, Neuhaus P, Pratschke J. Novel Candidate Markers Characterizing Cellular Senescence in Aged Zero Hour Kidney Biopsies Predict Post Transplant Outcome [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/novel-candidate-markers-characterizing-cellular-senescence-in-aged-zero-hour-kidney-biopsies-predict-post-transplant-outcome/. Accessed May 14, 2025.« Back to 2013 American Transplant Congress