Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation

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.