Gene Expression Profiling in Kidney Transplant Correlation with DGF

DIEGO GUERRIERI, LUIS RE, JORGELINA PETRONI, EDUARDO CHULUYAN, INCARDONA CLAUDIO, CASADEI H. DOMINGO

Congreso; American Transplant Congress; 2011

[607] Gene Expression Profiling in Kidney Transplant Correlation with DGF. Diego Guerrieri, Luis Re, Jorgelina Petroni, Eduardo Chuluyan, Incardona Claudio, Casadei H. Domingo. Farmacología, Facultad de Medicina, UBA, Argentina; Instituto de Nefrología Buenos Aires, Argentina; GADOR S.A., Buenos Aires, Argentina Introduction: Ischemia reperfusion injury (IRI) is a coordinated process leading to delayed graft function (DGF) and reduced long-term graft survival of the transplanted organ. Despite recent advances in organ procurement management, DGF remains an important problem after kidney transplantation. Different studies have related various clinical factors to DGF, such as donor age, recipient age, cold ischemia time (CIT) and initial immunosuppressive regimens. Objective and methods: The aim of the present study was to determine if the development of DGF was associated with a specific pattern of gene expression in deceased donor kidney transplantation and, if it was the case, to explore the presence of correlations b/w some transplant characteristics (CIT, donor & recipient age) and the profile that was found. The study included 16 recipients of deceased renal grafts (11 males, 5 females): 12 of them developed DGF and 4 patients show normal graft function(Table 1). A pathway-specific cDNA microarray was used for gene expression profiling and results were correlated with protocol biopsies 7 day post-transplant. Group 1 (DGF, n=12) Group 2(no DGF, n=4) Donor Age 56,5±4.2 53.3±2.2 Recipient Age 53.4±10.5 40.5±10.2 HLA MM(A, B, DR) 3.3±1.3 3.3±1.5 CIT 24±6 21±4 Results: From a total of 84 genes analyzed, 50 genes were up-regulated while only 1 gene was down-regulated in subjects with DGF compared with no DGF (p=0.01). Table 2 shows the most relevant genes fold changes observed based on DGF occurence. Mediators Fold of Change Up-regulated IL-1R1 4.9 IL-10 4.8 IFNA1 4.4 IL-1F7 4.3 CCR3 4.08 TLR8 3.5 IL-6 3 HMOX-1 2.9 TNF-α 2.7 Down-regulated TGF-β1 3.3 Although, a pro-inflammatory profile was up-regulated in DGF patients compared with no DGF, none of the transplant characteristics (CIT, donor & recipient age) were correlated with this gene array profile. Conclusions: A systematic biological assessment of these molecular changes suggests that the inflammatory process driven by IRI is largely responsible for DGF occurrence. DGF was associated in our study with an up-regulation of certain pro-inflammatory genes and a down-regulation of some anti-inflammatory mediators.