Pre-Transplant Recipient Transcriptomic Profile May Predict Delayed Graft Function (DGF) in Kidney Transplantation.
1University of Bari, Bari, Italy
2University of Foggia, Foggia, Italy
3University of Verona, Verona, Italy
Meeting: 2017 American Transplant Congress
Abstract number: D25
Keywords: Gene expression, Graft function, T cells
Session Information
Session Name: Poster Session D: Diagnostics/Biomarkers Session II
Session Type: Poster Session
Date: Tuesday, May 2, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background: DGF is associated with a reduced long-term graft survival. Ischemia-reperfusion damage and donors' features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the role of recipients' characteristics in the development of DGF.
Methods: We prospectively enrolled 538 kidney graft recipients, 176 of whom experienced DGF. We selected 10 couples of DGF/early graft function (EGF) recipients for high throughput analysis. Peripheral blood mononuclear cells (PBMC) were harvested before transplantation. Transcriptomic profile was investigated by HG-U133A microarray (Affymetrix). The results were evaluated by statistical (Genespring software) and functional pathway analysis (Ingenuity Pathway Analysis). The transcriptomic data were validated by qPCR in an independent group (DGF n=20; EGF n=20).
Results: In 38 cases both recipients from the same donor presented with DGF (C group), whereas in 138 cases only one recipient/donor experienced DGF (D group), suggesting a key role of recipients features in the pathogenesis of this condition. We did not observe any difference in donors' features between C and D group, further supporting our working hypothesis. In the D group, DGF was independently associated (logistic regression) only with number of mismatches (OR 1.867, p=0.01) and dialysis vintage (months, OR 1.009, p=0.03). The transcriptomic profile demonstrated that 273 genes were differentially expressed between the 2 groups, considering a fold change>2. The main biological functions were inflammatory disease (p range=9.8E-05-1.4E-14, 65 genes) and inflammatory response (p range=3.6E-04-3.2E-14, 80 genes), featuring the immunological profile of dialysis patients. Interestingly, Among the differentially expressed genes in DGF patients we observed a significant increase in the expression of CCR2 (FC=2.081), the receptor of the chemiotactic chemokine MCP-1, which could promote the recall of inflammatory cells in the graft, promoting DGF. CCR-2 increase was further validate by qPCR in an independent cohort of patients (p<0.02).
Conclusions: Our results suggest that recipients' immunological features, modulated by dialysis, are significantly associated with the development of DGF independently of donors' features.
CITATION INFORMATION: Pontrelli P, Rascio F, Pesce F, Accetturo M, Castellano G, Zaza G, Lupo A, Fiorentino M, Gesualdo L, Stallone G, Grandaliano G. Pre-Transplant Recipient Transcriptomic Profile May Predict Delayed Graft Function (DGF) in Kidney Transplantation. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Pontrelli P, Rascio F, Pesce F, Accetturo M, Castellano G, Zaza G, Lupo A, Fiorentino M, Gesualdo L, Stallone G, Grandaliano G. Pre-Transplant Recipient Transcriptomic Profile May Predict Delayed Graft Function (DGF) in Kidney Transplantation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/pre-transplant-recipient-transcriptomic-profile-may-predict-delayed-graft-function-dgf-in-kidney-transplantation/. Accessed December 12, 2024.« Back to 2017 American Transplant Congress