1. Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation
- Author
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Christian Koppelstaetter, Robert Öllinger, Gert Mayer, Johannes Hofer, Christoph Schwarz, Paul Perco, Alexander Kainz, Rainer Oberbauer, Christa Mitterbauer, Walter Mark, Andrzej Wiecek, Henryk Karkoszka, Bernd Mayer, and Gabriele Schratzberger
- Subjects
Adult ,Cyclin-Dependent Kinase Inhibitor p21 ,Male ,Aging ,medicine.medical_specialty ,Pathology ,Time Factors ,Biopsy ,Urology ,Cellular senescence ,Biology ,Kidney ,chemistry.chemical_compound ,CDKN2A ,medicine ,Humans ,Transplantation, Homologous ,Postoperative Period ,Cellular Senescence ,Cyclin-Dependent Kinase Inhibitor p16 ,Kidney transplantation ,Demography ,Creatinine ,medicine.diagnostic_test ,Cell Biology ,Middle Aged ,Telomere ,Cell cycle ,medicine.disease ,Kidney Transplantation ,Tissue Donors ,Transplantation ,Treatment Outcome ,chemistry ,Regression Analysis ,Female ,Biomarkers - Abstract
Summary Although chronological donor age is the most potentpredictor of long-term outcome after renal transplantation,it does not incorporate individual differences of the aging-process itself. We therefore hypothesized that an estimateof biological organ age as derived from markers of cellularsenescence in zero hour biopsies would be of higherpredictive value. Telomere length and mRNA expressionlevels of the cell cycle inhibitors CDKN2A (p16INK4a) andCDKN1A (p21WAF1) were assessed in pre-implantationbiopsies of 54 patients and the association of these andvarious other clinical parameters with serum creatinineafter 1 year was determined. In a linear regression analysis,CDKN2A turned out to be the best single predictorfollowed by donor age and telomere length. A multiplelinear regression analysis revealed that the combinationof CDKN2A values and donor age yielded even higherpredictive values for serum creatinine 1 year after trans-plantation. We conclude that the molecular aging markerpredict renal allograft function after 1 year significantlybetter than chronological donor age alone.Key words: biological organ age, CDKN1A, CDKN2A, kidneytransplantation, long-term allograft function, telomerelength, zero hour biopsy.
- Published
- 2008