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Delayed graft function (DGF), is associated with inferior graft outcomes. Whether poor graft function without dialysis, termed slow graft function (SGF), affects outcomes is unclear. We investigated associations between SGF (serum creatinine dropping by less than 30% between days 1 and 2), DGF and graft outcomes by donor type in a cohort of 17,579 Australian and New Zealand kidney transplant recipients from 2001–2021. The primary outcomes were graft survival and death-censored graft survival Compared with immediate graft function, both SGF (Adjusted hazard ratio [aHR] 1.48 (95% CI 1.14–1.91) and DGF [aHR 1.97 (1.42–2.73)] were associated with reduced graft survival in living donor and donation after brain death (DBD) recipients [SGF aHR 1.13 (1.01–1.27); DGF aHR 1.37 (1.24–1.51)]. In donation after circulatory death (DCD) recipients, DGF [(aHR 1.52 (1.13–2.04)] but not SGF [(aHR 1.55 (1.13–2.13)] was associated with reduced graft survival. Findings were similar for death-censored graft survival. In secondary analyses, SGFwas associated with reduced patient survival in living donor recipients. SGF and DGF were associated with lower 12-month eGFR for all donor types. DGF increased the odds of rejection for all donor types; for SGF this association was significant only for DBD recipients. SGF is associated with adverse outcomes in live donor and DBD kidney recipients.

Recipients of donation after circulatory death (DCD) kidneys are at high risk for delayed graft function (DGF) due to severe ischemia-reperfusion injury. We compared urinary biomarkers in predicting the duration of DGF with the tubular function slope (TFS) as the gold standard. In 89 DCD kidney transplant recipients, urinary TIMP-2, IGFBP7, B2M, NGAL, KIM1, CXCL9, and UMOD were quantified by LC-MS/MS analysis on postoperative days (PODs) 1, 4 and 10. Interstitial fibrosis and tubular atrophy (IF/TA) were assessed with protocol biopsies at POD 10. TFS was calculated with 99m Tc-MAG3 renography. Predictive performance was compared with AUCs from ROC analyses. Of all 89 recipients, 22% experienced no (<7), 22% mild (≥7–14), 29% moderate (≥14-<21) and 26% severe (≥21 days) fDGF. The OR for the presence of IF/TA was 1.9 (95% CI:0.4; 10.0) for mild to moderate and 15.0 (95% CI:2.7; 84.8) for severe compared to no fDGF. At POD 4, urinary NGAL and fractional NGAL excretion (FE-NGAL) outperformed TFS and other biomarkers in predicting fDGF with AUCs of 0.97, 0.98 and 0.92, respectively. At POD10, FE-NGAL and PCR best predicted severe vs . mild to moderate fDGF, with AUCs of 0.74 and 0.76 versus 0.65 for TFS. Therefore, urinary NGAL and FE-NGAL may provide a viable alternative to 99m TcMAG3 renography for monitoring fDGF clearance or guiding kidney transplant biopsy to exclude additional acute rejection.

Delayed graft function (DGF) in kidney transplantation is associated with ischemic injury and carries long term functional and immunological risks. Extracellular vesicles (EV) released from allografts may signal a degree of ischemic stress, and are thought to play an important role in the development of anti-donor immunity. Here, we show that kidney perfusate-derived extracellular vesicles (KP-EV) express donor-specific human leukocyte antigen. KP-EV from kidneys that experience DGF increase the T-helper 17 (Th17) to T-regulatory (Treg) ratio in third party peripheral blood mononuclear cells to a greater degree than those from kidneys with immediate function. We report miR-218-5p upregulation in KP-EV of kidney transplant recipients with DGF. Levels of miR-218-5p in KP-EV inversely correlated with recipient eGFR at multiple time points following transplantation. Additionally, the degree of increase in Th17/Treg ratio by KP-EV positively correlated with miR-218-5p expression in KP-EV samples. Taken together, these data provide evidence that KP-EV may contribute to modulating immune responses in transplant recipients. This could lead to novel intervention strategies to inhibit DGF in order to improve graft function and survival.

Background Preventing ischemia‒reperfusion injury (IRI) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRI is delayed graft function (DGF). Hypoxia is one of the key factors in IRI, suggesting that the use of an oxygen carrier as an additive to preservation solution may be useful. In the OxyOp trial, we showed that the organs preserved using the oxygen carrier HEMO2life® displayed significantly less DGF. In the OxyOp2 trial, we aim to definitively test and quantify the efficacy of HEMO2life® for organ preservation in a large population of kidney grafts. Methods OxyOp2 is a prospective, multicenter, randomized, comparative, single-blinded, parallel-group study versus standard of care in renal transplantation. After the selection of a suitable donor according to the inclusion/exclusion criteria, both kidneys will be used in the study. Depending on the characteristics of the donor, both kidneys will be preserved either in static cold storage (standard donors) or on machine perfusion (for ECD and deceased-after-cardiac-death donors (DCD)). The kidneys resulting from one donor will be randomized: one to the standard-of-care arm (organ preserved in preservation solution routinely used according to the local practice) and the other to the active treatment arm (HEMO2life® on top of routinely used preservation solution). HEMO2life® will be used for ex vivo graft preservation at a dose of 1 g/l preservation solution. The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation. Discussion The use of HEMO2life® in preservation solutions is a novel approach allowing, for the first time, the delivery of oxygen to organs. Improving graft survival by limiting ischemic lesions is a major public-health goal in the field of organ transplantation. Trial registration ClinicalTrials.gov, ID: NCT04181710 . registered on November 29, 2019.

Background/Objectives: Delayed graft function (DGF) is a major complication after kidney transplantation, affecting graft and patient survival. Although well-studied in Western populations, data from Eastern Europe are limited, and the prognostic significance of DGF severity, particularly renal replacement therapy (RRT) duration, is not well-defined. Methods: We conducted a retrospective analysis of 479 adult recipients of brain-dead donor (DBD) kidney transplants at a high-volume transplant center in Romania (2017–2024). DGF was defined as the need for dialysis within seven days’ post-transplant. Baseline characteristics, graft function, and survival outcomes were compared between DGF and non-DGF groups. Kidney function was evaluated using the Estimated Glomerular Filtration Rate (eGFR). Patient and graft survival were assessed using Kaplan–Meier curves and log-rank tests. DGF severity was stratified by RRT duration (≤14 vs. >14 days). Results: DGF occurred in 28.8% of patients (adjusted 24%). Those with DGF had a higher Body Mass Index (BMI), greater comorbidity (Charlson Index, Estimated Post-Transplant Survival (EPTS) score), longer pre-transplant dialysis, and higher Kidney Donor Profile Index (KDPI) donor kidneys. DGF was associated with lower graft survival at one, three, and five years and reduced patient survival at three and five years. Longer RRT was associated with progressively worse outcomes, with the poorest prognosis in patients needing >14 days. Conclusions: Delayed graft function was significantly associated with reduced graft and patient survival. Prolonged DGF time was found to be predictive for poorer outcomes.

Delayed graft function (DGF) is one of the key post-operative challenges for a subset of kidney transplantation (KTx) patients. Graft survival is significantly lower in recipients who have experienced DGF than in those who have not. Assessing the risk of chronic graft injury, predicting graft rejection, providing personalized treatment, and improving graft survival are major strategies for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of transplant medicine. However, since PPPM aims to accurately identify disease by integrating multiple omics, current methods to predict DGF and graft survival can still be improved. Renal ischemia/reperfusion injury (IRI) is a pathological process experienced by all KTx recipients that can result in varying occurrences of DGF, chronic rejection, and allograft failure depending on its severity. During this process, a necroinflammation-mediated necroptosis-dependent secondary wave of cell death significantly contributes to post-IRI tubular cell loss. In this article, we obtained the expression matrices and corresponding clinical data from the GEO database. Subsequently, nine differentially expressed necroinflammation-associated necroptosis-related genes (NiNRGs) were identified by correlation and differential expression analysis. The subtyping of post-KTx IRI samples relied on consensus clustering; the grouping of prognostic risks and the construction of predictive models for DGF (the area under the receiver operating characteristic curve (AUC) of the internal validation set and the external validation set were 0.730 and 0.773, respectively) and expected graft survival after a biopsy (the internal validation set’s 1-year AUC: 0.770; 2-year AUC: 0.702; and 3-year AUC: 0.735) were based on the least absolute shrinkage and selection operator regression algorithms. The results of the immune infiltration analysis showed a higher infiltration abundance of myeloid immune cells, especially neutrophils, macrophages, and dendritic cells, in the cluster A subtype and prognostic high-risk groups. Therefore, in the framework of PPPM, this work provides a comprehensive exploration of the early expression landscape, related pathways, immune features, and prognostic impact of NiNRGs in post-KTx patients and assesses their capabilities as. predictors of post-KTx DGF and graft loss, targets of the vicious loop between regulated tubular cell necrosis and necroinflammation for targeted secondary and tertiary prevention, and references for personalized immunotherapy.

Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies.

Background: to analyse the effect of haematological indices on the occurrence of Delayed Graft Function (DGF) in patients undergoing kidney transplantation and on the function of the transplanted kidney on the 7th postoperative day. Methods: 365 recipients who underwent kidney transplantation from a donor with known brain death between 2010 and 2017 were included in this retrospective study. Information from patient medical records, donor medical records, and donation and transplantation protocols was used for analysis. Statistica 13 was used for statistical analysis. Results: In the study group, DGF occurred in 144 recipients (39.45%), and Non-Graft Function (NGF) occurred in 12 recipients (3.29%). Recipients who developed DGF had a significantly higher Neutrophil/Monocyte Ratio (NMR) before renal transplantation (p = 0.048), a lower NMR value on postoperative day 1 (p < 0.001), and a difference between the values on day 1 and before surgery (p < 0.001). In addition, they had a significantly lower Lymphocyte/Monocyte Ratio (LMR) on postoperative day 1 LMR 1 (p < 0.001). It was shown that the value of the indices based on the ROC curve—NMR1 > 29.29, NMR1-0 > 22.71, and LMR1 > 1.74 (respectively: AUC = 0.624; 95% CI 0.566–0.682; and p < 0.001/AUC = 0.622; 95% CI 0.563–0.680; and p < 0.001/AUC = 0.610; 95% CI 0.550–0.670; and p < 0.001)—can be used to identify recipients with a significant probability of DGF. Conclusions: the NMR and LMR parameters on the first postoperative day and the difference between the NMR values on the first post-transplant day and the first pre-transplant day are predictive factors associated with the risk of DGF.

Background/Aims: Delayed graft function (DGF) is a common complication following kidney transplantation adversely affecting graft outcomes. Donation after brain death followed by circulatory death (DBCD), a novel donation pattern, is expected to correlate with high incidence of DGF. However, little information is available about factors associated with DGF in DBCD. Methods: A total of 383 kidney transplants from DBCD donation in three institutions were enrolled. Associations of DGF with the clinical characteristics of recipients and donors were quantified. Results: In this retrospective multi-center study, the incidence of DGF was 19.3%. Lower incidence of DGF was found in recipients for whom antithymocyte globulin was used for induction (p < 0.05), which was an independent protective factor against DGF (odds ratio [OR] = 0.48; 95% CI 0.27-0.86). Two novel explicative variables were recognized as independent risk factors, including use of vasoactive drugs (OR = 3.15; 95% CI 1.39-7.14) and cardiopulmonary resuscitation (OR = 2.51; 95% CI 1.05-6.00), which contributed significantly to increased risk of DGF (p < 0.05). Prolonged warm ischemia time (> 18 min; OR = 2.42; 95% CI 1.36-4.32), was also predictive of DGF in DBCD. A prediction model was developed and achieved an area under the curve of 0.89 in predicting DGF when combined with reported parameters. Conclusion: The novel factors, confirmed for the first time in our study, will help to improve risk prediction of DGF and to determine optimal interventions to prevent DGF in clinical practice.

Background Poor early graft function (EGF) after living donor kidney transplantation (LDKT) has been found to decrease rejection-free graft survival rates. However, its influence on long-term graft survival remains inconclusive. Methods Data were collected on 472 adult LDKTs performed between July 1996 and February 2010. Poor EGF was defined as the occurrence of delayed or slow graft function. Slow function was defined as serum creatinine above 3.0 mg/dL at postoperative day 5 without dialysis. Results The incidence of slow and delayed graft function was 9.3 and 4.4%, respectively. Recipient overweight, pretransplant dialysis and warm ischemia were identified as risk factors for the occurrence of poor EGF. The rejection-free survival was worse for poor EGF as compared to immediate graft function with an adjusted hazard ratio (HR) of 6.189 (95% CI 4.075–9.399; p  < 0.001). Long-term graft survival was impaired in the poor EGF group with an adjusted HR of 4.206 (95% CI 1.839–9.621; p  = 0.001). Conclusions Poor EGF occurs in 13.7% of living donor kidney allograft recipients. Both, rejection-free and long-term graft survivals are significantly lower in patients with poor EGF as compared to patients with immediate graft function. These results underline the clinical relevance of poor EGF as phenomenon after LDKT.