Pre-Transplant Expression of CCR-2 in Kidney Transplant Recipients Is Associated With the Development of Delayed Graft Function

Abstract

BackgroundDelayed graft function (DGF) leads to a reduced graft survival. Donors’ features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the recipients’ characteristics in the development of DGF.MethodsWe enrolled 932 kidney graft recipients from 466 donors; 226 recipients experienced DGF. In 290 donors, both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B), and in 126 one recipient presented with DGF and the other with EGF (group C). In group C, we selected 7 couples of DGF/EGF recipients and we evaluated the transcriptomic profile by microarray on circulating mononuclear cells harvested before transplantation. Results were validated by qPCR in an independent group of 25 EGF/DGF couples.FindingsIn the whole study group, DGF was associated with clinical characteristics related to both donors and recipient. In group C, DGF was significantly associated with body mass index, hemodialysis, and number of mismatches. In the same group, we identified 411 genes differently expressed before transplantation between recipients discordant for the transplant outcome. Those genes were involved in immune dysfunction and inflammation. In particular, we observed a significant increase in DGF patients in the expression of C–C chemokine receptor type 2 (CCR2), the monocyte chemoattractant protein-1 (MCP-1) receptor. CCR-2 upregulation was confirmed in an independent cohort of patients.ConclusionsOur results suggest that recipients’ clinical/immunological features, potentially modulated by dialysis, are associated with the development of DGF independently of donors’ features.

Kidney Survival Impact of Delayed Graft Function Depends on Kidney Donor Risk Index: A Single-Center Cohort Study

“…It underscores the necessity for continuous research efforts to unveil the underlying mechanisms that govern graft behavior in response to DGF. Additionally, there is a need to develop non-invasive diagnostic techniques and biomarkers to accurately predict the future implications of DGF [19,20].…”

Pretransplant characteristics of kidney transplant recipients that predict posttransplant outcome

“…Pontrelli et al showed that pretransplant transcripts of C-C chemokine receptor type 2 were higher in circulating mononuclear cells from 25 kidney transplant recipients with acute allograft injury compared to 25 controls, showing a sensitivity of 0.74 and a specificity of 0.68 (33). C-C chemokine receptor type 2, which is also called CD192, is the receptor for monocyte chemoattractant protein-1 which is involved in monocyte chemotaxis after tissue damage (33). If confirmed in future studies, potentially modifiable pretransplant biomarkers may help for kidney transplant allocation to reduce postoperative acute allograft injury.…”