Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation.
Although chronological donor age is the most potent predictor of long-term outcome after renal transplantation, it does not incorporate individual differences of the aging-process itself. We therefore hypothesized that an estimate of biological organ age as derived from markers of cellular senescence in zero hour biopsies would be of higher predictive value. Telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) were assessed in pre-implantation biopsies of 54 patients and the association of these and various other clinical parameters with serum creatinine after 1 year was determined. In a linear regression analysis, CDKN2A turned out to be the best single predictor followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values for serum creatinine 1 year after transplantation. We conclude that the molecular aging marker CDKN2A in combination with chronological donor age predict renal allograft function after 1 year significantly better than chronological donor age alone.
Koppelstaetter
Christian
C
Division of Nephrology, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.
Schratzberger
Gabriele
G
Perco
Paul
P
Hofer
Johannes
J
Mark
Walter
W
Ollinger
Robert
R
Oberbauer
Rainer
R
Schwarz
Christoph
C
Mitterbauer
Christa
C
Kainz
Alexander
A
Karkoszka
Henryk
H
Wiecek
Andrzej
A
Mayer
Bernd
B
Mayer
Gert
G
D000328:Adult; D000375:Aging / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016922:Cellular Senescence; D003404:Creatinine / Q000097:blood; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D003710:Demography; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D012044:Regression Analysis; D016615:Telomere / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D003404:Creatinine