Abstract
Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008–2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.
Highlights
Acute renal injury early after transplantation can lead to delayed graft function (DGF), increase the immunogenicity of the tissue and result in immunological rejection episodes requiring treatment [1].The reported incidence of DGF after deceased donor kidney transplantation varies between 5 and 50% and continues to grow as kidneys from elderly donors are increasingly used due to organ shortage [2,3,4,5]
These patients represented a random sample and a graft survival rate which was identical with that observed in 1,692 patients who were not included in the study, but received a deceased donor kidney transplant over the same time period at the same centers (Figure 1)
The results obtained in this large multicenter cohort of more than 1,700 deceased-donor kidney transplant recipients indicate that, in addition to well-known non-immunological factors, a broad level of sensitization prior to transplantation as reflected by the co-presence of human leukocyte antigens (HLA) class I and class II antibodies in patient’s serum increases the risk of DGF development despite the currently applied sensitive antibody testing
Summary
Acute renal injury early after transplantation can lead to delayed graft function (DGF), increase the immunogenicity of the tissue and result in immunological rejection episodes requiring treatment [1].The reported incidence of DGF after deceased donor kidney transplantation varies between 5 and 50% and continues to grow as kidneys from elderly donors are increasingly used due to organ shortage [2,3,4,5]. Earlier data from the Serum Study of the Collaborative Transplant Study (CTS) indicated that adverse events in deceased donor kidney transplantation, such as no immediate function and rejection episodes during the first 3 months post-transplant, are associated with pre-transplant presence of alloantibodies against human leukocyte antigens (HLA) [11]. Patients with these early adverse events showed significantly impaired graft survival rates. Small single-center studies indicated that donor-specific HLA antibodies (DSA) and rejection episodes are detrimental in patients with DGF, while more recent large-scale studies on an involvement of DSA in DGF are lacking [12, 13]
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