Abstract
Background: Better understanding of the contribution of donor aging and comorbidity factors of expanded criteria donors (ECD) to the clinical outcome of a transplant is a challenge in kidney transplantation. We investigated whether the features of donor-derived stromal vascular fraction of perirenal adipose tissue (PRAT-SVF) could be indicative of the deleterious impact of the ECD microenvironment on a renal transplant.Methods: A comparative analysis of cellular components, transcriptomic and vasculogenic profiles was performed in PRAT-SVF obtained from 22 optimal donors and 31 ECD deceased donors. We then investigated whether these parameters could be associated with donor aging and early allograft dysfunction.Results: When compared with the PRAT-SVF of non-ECD donors, ECD PRAT-SVF displayed a lower proportion of stromal cells, a higher proportion of inflammatory NK cells. The global RNA sequencing approach indicated a differential molecular signature in the PRAT-SVF of ECD donors characterized by the over-expression of CXCL1 and IL1-β inflammatory transcripts. The vasculogenic activity of PRAT-SVF was highly variable but was not significantly affected in marginal donors. Periorgan recruitment of monocytes/macrophages and NK cells in PRAT-SVF was associated with donor aging. The presence of NK cell infiltrates was associated with lower PRAT-SVF angiogenic activity and with early allograft dysfunction evaluated on day 7 and at 1 month post-transplant.Conclusions: Our results indicate that human NK cell subsets are differentially recruited in the periorgan environment of aging kidney transplants. We provide novel evidence that PRAT-SVF represents a non-invasive and timely source of donor material with potential value to assess inflammatory features that impact organ quality and function.
Highlights
Increasing recipient demand combined with inadequate organ supply has led to the use of suboptimal marginal kidneys from expanded criteria donors (ECD) with cardiovascular risk factors [1,2,3]
While the use of ECD kidney transplants enables more patients to benefit from renal transplantation, various studies have reported that marginal transplants from elderly donors are associated with an increased incidence of delayed graft function (DGF), slow graft function recovery (SGF) [3,4,5,6] and poorer long-term graft outcome [5, 7,8,9]
This study aimed to [1] provide a comprehensive view of cellular, transcriptomic, and angiogenic profiles that could characterize the peri-organ stromal vascular fraction (SVF) obtained from marginal kidney donors, and [2] analyze whether the features of perirenal adipose tissue (PRAT)-SVF could be indicative of the deleterious impact of donor aging and cardiovascular risk factors on early kidney allograft dysfunction
Summary
Increasing recipient demand combined with inadequate organ supply has led to the use of suboptimal marginal kidneys from expanded criteria donors (ECD) with cardiovascular risk factors [1,2,3]. While the use of ECD kidney transplants enables more patients to benefit from renal transplantation, various studies have reported that marginal transplants from elderly donors are associated with an increased incidence of delayed graft function (DGF), slow graft function recovery (SGF) [3,4,5,6] and poorer long-term graft outcome [5, 7,8,9]. The underlying mechanisms which associate donor age and cardiovascular risk factors with a worsened outcome of these marginal transplants are not completely understood. Better understanding of the contribution of donor aging and comorbidity factors of expanded criteria donors (ECD) to the clinical outcome of a transplant is a challenge in kidney transplantation. We investigated whether the features of donor-derived stromal vascular fraction of perirenal adipose tissue (PRAT-SVF) could be indicative of the deleterious impact of the ECD microenvironment on a renal transplant
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