Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria

PLoS One. 2013 Jul 4;8(7):e68133. doi: 10.1371/journal.pone.0068133. Print 2013.

Abstract

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post-transplant serum creatinine when compared to "Gold Standard" clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function. It also shows that CDKN2A is as strong a determinant of post-transplant organ function when compared to extended criteria (ECD) kidneys. A multivariate analysis model was able to predict up to 27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was also able to strongly predict delayed graft function. A pre-transplant donor risk classification system based on CDKN2A and ECD criteria is shown to be feasible and commendable for implementation in the near future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Biomarkers / metabolism
  • Biopsy
  • Cold Ischemia
  • Creatinine / blood
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Delayed Graft Function / prevention & control
  • Female
  • Gene Expression*
  • Glomerular Filtration Rate
  • Humans
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Tissue Donors
  • Treatment Outcome

Substances

  • Biomarkers
  • Cyclin-Dependent Kinase Inhibitor p16
  • Creatinine

Grants and funding

This work was supported by Darlinda’s Charity for Renal Research (http://www.darlindascharity.co.uk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.