The definition of biological donor organ age rather than chronological age seems an obvious factor for the establishment of valid pre-transplant risk assessment. We therefore studied gene expression for candidate markers in 60 zero-hour kidney biopsies. Compared with younger donors (n=29, <55 years), elderly donors (n=31, ≥55 years) revealed strong mRNA expression of immunoproteasome subunits (PSMB8, p=0.0004; PSMB9 and PSMB10, p<0.0001, respectively), HLA-DRB (p=0.0030) or transcripts of the receptor NKG2D (p=0.0046). Gene expression was validated in an independent donor cohort (n=187) and the following groups were defined: (I) ≤30 years (n=37), (II) 31-54 years (n=75) and (III) ≥55 years (n=75). Gene induction was confirmed in aged kidneys (Group III) for PSMB9 (p=0.0080) and PSMB10 (p=0.0017). Strikingly, transcripts of NKG2D revealed the highest gene induction in Group III versus Group II (p=0.0002) and Group I (p<0.0001). Similar results were obtained for CDKN2A, but not for telomere length. NKG2D and CDKN2A mRNA expression was correlated with creatinine levels at 24 months after transplantation (p<0.005 and p=0.018). Univariate regression analysis showed significant predictive power regarding graft function at 6 and 12 months for NKG2D and CDKN2A however, only NKG2D remained significantly predictive in the multivariate model at 12 months (p=0.0078). Our results reveal novel candidate markers in aged renal allografts, which could be helpful in the assessment of organ quality.

CITATION INFORMATION: Resch T, Günther J, Hackl H, Sattler A, Ebner S, Ritschl P, Biebl M, Öllinger R, Schneeberger S, Brandacher G, Schwelberger H, Zelger B, Stauch D, Pascher A, Pratschke J, Kotsch K. Identification of NKG2D as Senescence Marker in Zero-Hour Kidney Biopsies Is Indicative for Clinical Outcome. Am J Transplant. 2017;17 (suppl 3).

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