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.

The aim of this study was to determine the frequency of exposure to different sensitizing events (SEs) and to assess their effects on human leucocyte antigen (HLA) alloimmunization in transplant candidates using two different HLA antibody screening techniques: complement-dependent cytotoxicity (CDC) and Luminex. This retrospective study included HLA antibody screening results for 163 patients on the kidney transplant waiting list (WL) tested from March 2012 until the end of December 2015 at the Tissue Typing Laboratory, Rijeka, Croatia. All sera samples were tested using the CDC and Luminex techniques in parallel. Two-thirds of the patients [114 (70%)] on the WL were exposed to transfusions, pregnancies and/or kidney transplant. The pre-transplant sera of 104 (63.80%) patients were negative for antibodies. In the sera of 23 (14.11%) patients, HLA antibodies were detected by CDC and Luminex and in the sera of 36 (22.09%) patients by Luminex only. In patients on kidney WL, previous organ transplantation represents the strongest immunogenic stimulus, followed by blood transfusions (the most frequent SE) and pregnancies. Although Luminex is more sensitive than CDC in HLA antibody detection, the decision on unacceptable HLA antigens in WL patients has to be based on the results of both assays and the patient’s immunization history.

Objectives: Computerized tomography (CT) is the most accurate method for evaluating pelvic calcifications, which are of utmost importance for planning kidney transplantation (KT). The aim of our study was to evaluate the incidence and distribution of iliac artery calcifications and correlate the novel pelvic calcification score (PCS) with cardiovascular risk factors and graft and overall survival in KT patients. Methods: We retrospectively included 118 KT patients operated at our institution with pretransplant pelvic CT. Calcification morphology, circumference and length of both common and external iliac arteries were independently scored by two uroradiologists. PCS was calculated as the total score sum of all three calcification features in all vessels. PCS correlation with graft and patient survival was performed. Results: Calcification in at least one vascular segment was found in 79% of patients. PCS was significantly higher in male patients (p = 0.006), patients over 55 years (p < 0.001), and patients on haemodialysis (p = 0.016). Patients with a PCS >3 had significantly shorter graft and overall survival rates (p = 0.041 and p = 0.039, respectively). Conclusions: The extent of iliac artery calcification in KT recipients quantified by PCS on pretransplant CT correlates with graft and overall patient survival. A PCS over three was associated with worse clinical outcomes and could become a possible prognostic factor. Advances in knowledge: Our novel PCS is a robust method for quantifying iliac artery calcification burden. Since higher a PCS correlates with worse patient and graft survival, PCS has the potential to become a prognostic factor in kidney transplant patients.

Background: Vascular calcifications (VC) are increasingly prevalent in patients with chronic kidney disease. This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and explore the relationship between iliac VC burden measured by pelvic calcification score (PCS) and renal transplant outcomes. Methods: This prospective study involved 79 KT recipients. VC quantification, using a pre-transplant computed tomography (CT) scan, was performed by assessing calcifications in the common and external iliac arteries bilaterally, resulting in an overall PCS ranging from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups: PCS Group 1 (PCS 0–4), PCS Group 2 (PCS 5–19), and PCS Group 3 (PCS > 19). Post-transplant outcomes tracked for at least 1 year were patient and graft survival, graft function (urea, creatinine, MAG-3 clearance), and incidence of MACE during the first post-transplant year. Results: Calcifications were present in at least one arterial segment in 61 patients (77.2%). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients in PCS Group 3 had significantly lower one-year patient and graft survival compared to those in PCS Group 1 and 2 (p = 0.006 and p = 0.008, respectively). MACE and renal function indicators 1-year post-transplant were similar across all PCS groups. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibited iliac VC during pre-transplant CT assessments. Patients in PCS Group 3 exhibited significantly lower one-year patient and graft survival rates compared to those in PCS Groups 1 and 2, indicating that this subgroup may require more intensive post-transplant monitoring and management.

The Human Leukocyte Antigen (HLA) system forms the central part of the immune system and is crucial in the recognition and elimination of “non-self” antigens. While this role of the HLA system is essential in the effective defense of the organism against pathogens, it is undesirable in organ and tissue transplantation because it enables the recognition of mismatched HLA molecules of the donor as being foreign and stimulates the graft rejection reaction. Organ transplantation involves the introduction of antigens that are more or less mismatched to the recipient; therefore, in order to achieve the best possible match in the HLA system between the recipient and the donor, a whole series of immunogenetic tests is performed, including crossmatching (XM). If performed before kidney transplantation, it represents the final in vitro test to rule out the presence of donor-specific antibodies, which may cause graft rejection and which may not have been detected by earlier serum screening. The beginning of XM was marked by the complement-dependent cytotoxicity (CDC) method developed by Terasaki and colleagues in 1964. Later, as a result of advances in technology and the need for methods that overcome the limitations of CDC, flow cytometry and Luminex XM assays were developed. The introduction of solid-phase technology brought a new dimension to the detection of low-level HLA antibodies and the determination of their specificities, which enabled the development and implementation of the virtual XM test (vXM). It is an in silico test that assesses the immunological match between the recipient and the organ donor based on the analysis of the specificity of the antibodies present in the recipient’s serum and the HLA typing of the organ donor. Each method has its own advantages and limitations, which are described below and need to be taken into account, considering their significant impact on clinical application in kidney transplantation.