Identification of the activating cytotoxicity receptor NKG2D as a senescence marker in zero-hour kidney biopsies is indicative for clinical outcome

Kidney Int. 2017 Jun;91(6):1447-1463. doi: 10.1016/j.kint.2016.12.018. Epub 2017 Feb 22.


The definition of biological donor organ age rather than chronological age seems obvious for the establishment of a valid pre-transplant risk assessment. Therefore, we studied gene expression for candidate markers in 60 zero-hour kidney biopsies. Compared with 29 younger donors under age 55, 31 elderly donors age 55 and older had significant mRNA expression for immunoproteasome subunits (PSMB8, PSMB9 and PSMB10), HLA-DRB, and transcripts of the activating cytotoxicity receptor NKG2D. Gene expression was validated in an independent donor cohort consisting of 37 kidneys from donors 30 years and under (Group I), 75 kidneys from donors age 31-54 years (Group II) and 75 kidneys from donors age 55 and older (Group III). Significant gene induction was confirmed in kidneys from Group III for PSMB9 and PSMB10. Strikingly, transcripts of NKG2D had the significantly highest gene induction in Group III versus Group II and Group I. Similar results were obtained for CDKN2A, but not for telomere length. Both NKG2D and CDKN2A mRNA expression were significantly correlated with creatinine levels at 24 months after transplantation. 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. Thus, our results reveal novel candidate markers in aged renal allografts, which could be helpful in the assessment of organ quality.

Keywords: NKG2D; kidney; senescence; zero-hour biopsy.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Austria
  • Biopsy
  • Cellular Senescence*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • Cysteine Endopeptidases / genetics
  • Delayed Graft Function / genetics
  • Donor Selection*
  • Female
  • Gene Expression Regulation
  • Genetic Markers
  • Germany
  • Graft Rejection / genetics
  • Graft Survival
  • HLA-DR beta-Chains / genetics
  • Humans
  • Kidney / chemistry*
  • Kidney / pathology
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • NK Cell Lectin-Like Receptor Subfamily K / genetics*
  • Predictive Value of Tests
  • Proteasome Endopeptidase Complex / genetics
  • RNA, Messenger / genetics
  • Risk Factors
  • Telomere Homeostasis
  • Time Factors
  • Tissue Donors*
  • Treatment Outcome
  • Young Adult


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • Genetic Markers
  • HLA-DR beta-Chains
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • RNA, Messenger
  • LMP-2 protein
  • Cysteine Endopeptidases
  • LMP7 protein
  • PSMB10 protein, human
  • Proteasome Endopeptidase Complex