RESUMEN
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.
Asunto(s)
Senescencia Celular , Selección de Donante , Trasplante de Riñón/métodos , Riñón/química , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Donantes de Tejidos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Austria , Biopsia , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , Cisteína Endopeptidasas/genética , Funcionamiento Retardado del Injerto/genética , Femenino , Regulación de la Expresión Génica , Marcadores Genéticos , Alemania , Rechazo de Injerto/genética , Supervivencia de Injerto , Cadenas beta de HLA-DR/genética , Humanos , Riñón/patología , Trasplante de Riñón/efectos adversos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Complejo de la Endopetidasa Proteasomal/genética , ARN Mensajero/genética , Factores de Riesgo , Homeostasis del Telómero , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: This manuscript reviews the data about the histopathologic and develops recommendations to standardise and improve the biopsy procedure, the biopsy handling, the histopathological evaluation, the communication of results and the collection of data from pretransplantation kidney biopsies of deceased donors in Germany. METHODS: The recommendations are based on this literature review, on discussions at two workshops held by the German Society of Pathology and the German Organ Transplantation Foundation and on personal experiences of the authors. RESULTS: These German recommendations advocate the use of punch biopsies, paraffin embedding and detailed descriptive reporting of histopathological findings. CONCLUSIONS: These recommendations constitute only a starting point. Periodical revisions will help to simplify and optimise the recommendations with the ultimate goal to prospectively gather data for the elaboration of a computer-based algorithm that allows the exact prediction of transplantation outcome for a given match of donor and recipient.