Occurrence Of Delayed Graft Function Research Articles

#569 Proenkephalin A 119-159 (penKid) for the early identification and risk stratification of delayed graft function following kidney transplantation

Abstract Background and Aims Delayed graft function (DGF) frequently occurs following kidney transplantation, and prolonged duration of DGF adversely affects 1-year graft function and long-term graft survival. Recently, Proenkephalin A 119-159 (penKid) was shown to reflect kidney function and predict acute kidney injury (AKI) in critically ill patients. Given the similarities between DGF in transplanted and AKI in native kidneys, we hypothesized that penKid may aid in identifying and risk-stratifying DGF post-transplantation. Method In a prospective study of 159 consecutive kidney transplant recipients at Heidelberg University Hospital from November 2021 to July 2023, penKid was quantified using an immunoluminometric assay until patient discharge. DGF was primarily defined as the necessity for dialysis within 7 days post-transplant. Additionally, penKid was examined in the context of DGF severity, discriminating the different durations of post-transplant dialysis treatment. Similarly, penKid was assessed to differentiate uptake of graft function, defined as slow or immediate by a serum creatinine reduction ratio of pre-transplant and 7 days post-transplant levels of <0.7 and ≥0.7, respectively. Results DGF, defined as the need for dialysis within the first week post-transplant, occurred in 53/159 (33.3%) patients. penKid enabled the differentiation of patients with and without DGF from the first day post-transplant onward (P < 0.001, Fig. 1), and consistently outperformed SCr in discriminating DGF from no DGF at all time points studied (P < 0.001). Additionally, penKid allowed identification of DGF severity from the first day post-transplant (P < 0.001) and early differentiation between slow and delayed graft function (AUC 0.79 [95% CI 0.68-0.90]). In a multivariate model, delta penKid from pre-transplant to the first day post-transplant emerged as the strongest predictor for DGF (C index = 0.88). On the first day post-transplant, penKid, with a cut-off at 300 pmol/L, discriminated DGF from no DGF with a sensitivity of 95.1% (95% CI 83.9–98.7) and a specificity of 56.5% (95% CI 46.3–66.2). Conclusion penKid is a promising biomarker shown to accurately differentiate DGF from no DGF as early as the first day post-transplant and to predict DGF severity, allowing for earlier intervention in these at-risk patients. Due to its high discriminatory power to identify and predict DGF post-transplantation, penKid shows great potential to accompany future studies examining the occurrence of DGF in transplant programs, where DCD is introduced into practice, machine perfusion techniques are assessed, or in trials that assess potential therapeutic interventions in patients with DGF.

Untargeted NMR-based metabolomics analysis of kidney allograft perfusates identifies a signature of delayed graft function.

Kidney transplantation (KTx) necessarily conveys an ischemia/reperfusion (I/R) process, which impacts on allograft outcomes. Delayed graft function (DGF) is defined as a non-decrease of serum creatinine by at least 10% daily on 3 consecutive days during the first 7days post-KTx. DGF significantly conditions both short- and long-term graft outcomes. Still there is a lack of DGF predictive biomarkers. This study aimed to explore the potential of kidney graft perfusate metabolomics to predict DGF occurrence. 49 human perfusates from grafts categorized upon donor type [donation after brain death (DBD)/donation after circulatory death (DCD)] and DGF occurrence and 19 perfusates from a murine model classified upon death type (DBD/DCD) were collected and analyzed by NMR-based metabolomics. The multivariate analysis of the murine data highlighted significant differences between perfusate metabolomes of DBD versus DCD. These differences were similarly observed in the human perfusates. After correcting for the type of donor, multivariate analysis of human data demonstrated a metabolomics signature that could be correlated with DGF occurrence. The metabolome of kidney grafts is influenced by the donor's type in both human and pre-clinical studies and could be correlated with DGF in the human DBD cohort. Thus, metabolomic analysis of perfusate applied prior to KTx may represent a new predictive tool for clinicians in a more personalized management of DGF. Moreover, our data paves the way to better understand the impact of donor's types on the biochemical events occurring between death and the hypothermic storage.

Early post-operative lactate increase following kidney transplant is associated with delayed graft function: A retrospective cohort study.

Delayed graft function (DGF) is a frequent complication following kidney transplant. This study aimed to assess the association between early post-operative lactate variation and DGF. This was a single center, retrospective cohort study between February 2021 and December 2022 in Saint-Louis Hospital (APHP, France). Venous lactate levels were measured immediately (H0) and 4h (H4) after kidney transplant. The primary outcome was the occurrence of DGF (need for renal replacement therapy between transplantation and day 7). Secondary outcome was the occurrence of complications (i.e., death, vascular thrombosis, hemorrhagic shock, urological complications (hematoma, urinoma), local or systemic infection) between transplant and day 7. Two hundred 12 patients were included, and 38 (17.9%) developed DGF. Venous lactate variation between H0 and H4 was higher in patients who developed DGF (-30 (IQR -83, -6)% vs. -15 (IQR -62, -11)%, p=.037), but the variation of level was more often positive (corresponding to an increased lactate production over time between H0 and H4) in patients who developed DGF ((28(85%) vs. 94(62%), p=.011). In multivariate logistic regression, positive venous lactate level variation between H0 and H4 was strongly associated with a reduced risk of developing DGF (OR .30 [.09-.79], p=.024). We did not find any association between post-operative hyperlactatemia and occurrence of complications between transplant and day 7. DGF is a frequent complication following kidney transplantation. Its early prediction could help physicians optimize treatment and protect the kidney. Early venous lactate variation after kidney transplant could help to predict the occurrence of DGF.

Association between peri-transplant acid-base parameters and graft dysfunction types in kidney transplantation.

Perioperative acid-base disturbance could be informative regarding the possible slow graft function (SGF) or delayed graft function (DGF) development. There is a lack of data regarding the relationship between perioperative acid-base parameters and graft dysfunction in kidney transplant (KT) recipients. We aim to determine the incidence of graft dysfunction types and the association between them and acid-base parameters. We performed a prospective, cohort study on 54 adults, KT recipients, between 1st of January 2019 and 31st of December 2019. Graft function was defined and classified in three categories: immediate graft function (IGF) (serum creatinine < 3 mg/dL at day 5 after KT), SGF (serum creatinine ≥ 3mg/dL at day 5 or ≥ 2.5mg dL at day 7 after KT) and DGF (the need for at least one dialysis treatment in the first week after kidney transplantation). Among the 54 KT recipients, the incidence of SGF and DGF was 13% and 11.1%, respectively. SGF was significantly associated with lower intraoperative pH (7.26± 0.05 vs 7.35± 0.06, p= 0.004), preoperative and intraoperative base excess (BE) [-7.0 (-10.0 ߝ -6.0) vs -3.4 (-7.8 ߝ - 2.1) mmol/L, p= 0.04 and -10.3 (-11.0 ߝ -9.1) vs -4.0 (-6.3 ߝ - 3.0) mmol/L, p= 0.002, respectively] and serum bicarbonate (HCO3-) (16.0± 2.7 vs 19.3± 3.4 mmol/L, p= 0.01 and 14.1± 1.9 vs 18.8± 3.2 mmol/L, p= 0.002 respectively), compared to IGF. DGF was significantly associated with lower intraoperative values of pH (7.27± 0.05 vs 7.35± 0.06, p= 0.003), BE [-7.1 (-10.9 ߝ -6.1) vs -4.0 (-6.3 ߝ - 3.0) mmol/L, p= 0.02] and HCO3- (15.9± 2.4 vs 18.8± 3.2 mmol/L, p=0.02) compared to IGF. No differences were observed between SGF and DGF patients in any of the perioperative acid-base parameters. In conclusion we found that kidney graft dysfunction types are associated with perioperative acid-base parameters and perioperative metabolic acidosis could provide important information to predict SGF or DGF occurrence.

Duration of Dialysis in Acute Kidney Injury Donors and Transplant Outcomes.

Acute kidney injury (AKI) kidneys, including those from donors on dialysis, are often underutilized, although there is increasing data available demonstrating good transplant outcomes. To date, data on the duration of donor dialysis and transplant outcomes are limited. This was a single-center study of deceased donor kidney transplants from 2010 to 2022. The study cohort consisted of recipients of deceased donor kidney transplants from donors with AKI and on dialysis. Three groups were identified based on the predetermined interquartile range of donor dialysis duration: 1 to 2 dialysis days, 3 to 4 dialysis days, and 5 or more dialysis days. During this period, 765 AKI deceased donor transplants were performed, of which 230 were from donors on dialysis. The median dialysis duration was 2 days with a maximum of 13 days. Across the 3 groups, there were no differences in recipient age (p = 0.23) or dialysis vintage (p = 0.70). Donor age (p = 0.86) and kidney donor profile index (p = 0.57) were comparable between the groups. Recipients of deceased donor kidney transplants from donors on dialysis 5 or more days had lower terminal creatinine levels (p = 0.003) and longer cold ischemia times (p = 0.04). Posttransplant, the median length of hospital stay was 3 days for all groups (p = 0.75). There were no differences in delayed graft function occurrence (94.4% vs 86.8% vs 92.1%, p = 0.19), duration of delayed graft function (p = 0.56), or readmissions (p = 0.99). At 1 year posttransplant, the estimated glomerular filtration rate (p = 0.76), patient survival (p = 0.82), or death-censored graft survival (p = 0.28) were comparable. Excellent outcomes have been observed in AKI deceased donor kidney transplants, including those coming from donors on dialysis. In this small cohort, the duration of donor dialysis did not adversely affect outcomes. Cautious expansion of the donor pool, including donors on dialysis, should be considered given the ongoing organ shortage.

Delayed Graft Function in Kidney Retransplantation: United Network for Organ Sharing Data With Linked Primary and Retransplant

IntroductionThere are several articles exploring the risk factors for primary delayed graft function (DGF). However, current literature does not include many resources on the risk factors for DGF when it is a recipient's second kidney transplant or look at short-term graft and patient survival of DGF retransplants. MethodsUnited Network for Organ Sharing data from January 2008 to June 2021 were analyzed. Pancreas transplants, multi-organ transplants, and lost to follow-up transplants were excluded. Second transplant patients with DGF were identified. Multivariate logistic regression models based on the primary and second transplant characteristics were created. Survival analysis was performed with Kaplan-Meier methodology and assessed with log-rank test. ResultsA total of 2964 second kidney transplants were identified. Rate of DGF in the second transplant was 28.4% (843/2964) and 49.2% of them had a prior DGF in their first transplant (P < 0.001). Multivariate analysis confirmed that occurrence of DGF (odds ratio [OR] 1.5, P < 0.001) and graft loss due to acute rejection (OR 1.2, P < 0.005) in the primary transplant were predictors of reappearing DGF in the second transplant. Dialysis at transplant was the greatest risk factor from the second transplant (OR 3.539, P < 0.001). There was a decreased graft survival after 12 mo (77% versus 49% with log t-test <0.001) in the second transplant. However, DGF was not significantly associated with patient survival. ConclusionsThis study shows the interaction between primary and second transplant in developing DGF. Survival analysis shows lower graft survival for retransplants in the case of DGF. This study opens the possibility of identifying additional risk factors for patients undergoing retransplant surgeries.

Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial

BackgroundPreventing 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.MethodsOxyOp2 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.DiscussionThe 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 registrationClinicalTrials.gov, ID: NCT04181710. registered on November 29, 2019.

Investigation of Different Methods of Intraoperative Graft Perfusion Assessment during Kidney Transplantation for the Prediction of Delayed Graft Function: A Prospective Pilot Trial.

Delayed graft function (DGF) after renal transplantation is a relevant clinical problem affecting long-term organ function. The early detection of patients at risk is crucial for postoperative monitoring and treatment algorithms. In this prospective cohort study, allograft perfusion was evaluated intraoperatively in 26 kidney recipients by visual and formal perfusion assessment, duplex sonography, and quantitative microperfusion assessment using O2C spectrometry and ICG fluorescence angiography. The O2C tissue spectrometry device provides a quantitative method of microperfusion assessment that can be employed during kidney transplantation as an easy-to-use and highly sensitive alternative to ICG fluorescence angiography. Intraoperative microvascular flow and velocity in the allograft cortex after reperfusion predicted DGF with a sensitivity of 100% and a specificity of 82%. Threshold values of 57 A.U. for microvascular flow and 13 A.U. for microvascular velocity were identified by an ROC analysis. This study, therefore, confirmed that impairment of microperfusion of the allograft cortex directly after reperfusion was a key indicator for the occurrence of DGF after kidney transplantation. Our results support the combined use of intraoperative duplex sonography, for macrovascular quality control, and quantitative microperfusion assessment, such as O2C spectrometry, for individual risk stratification to guide subsequent postoperative management.

Prediction model of delayed graft function based on clinical characteristics combined with serum IL-2 levels

BackgroundKidney transplantation is an effective treatment for end-stage renal disease (ESRD). Delayed graft function (DGF) is a common complication after kidney transplantation and exerts substantial effects on graft function and long-term graft survival. Therefore, the construction of an effective model to predict the occurrence of DGF is particularly important.MethodsSeventy-one patients receiving their first kidney transplant at the First Affiliated Hospital of Nanchang University from October 2020 to October 2021 were enrolled in the discovery cohort. Based on clinical characteristics and serum markers, a logistic regression model was used to simulate the risk of DGF in the discovery cohort. The DGF prediction model was named the prediction system and was composed of risk factors related to DGF. Thirty-two patients receiving a kidney transplant at the First Affiliated Hospital of Nanchang University from October 2021 to February 2022 were enrolled in the validation cohort. The validation cohort was used to verify the accuracy and reliability of the prediction model.ResultsCold ischemia time (CIT), donor history of diabetes mellitus, donor interleukin-2 (IL-2) level and donor terminal creatinine level constitute the prediction system. In the validation test, the area under the receiver operating characteristic curve (AUC) was 0.867 for the prediction system, and good calibration of the model was confirmed in the validation cohort.ConclusionsThis study constructed a reliable and highly accurate prediction model that provides a practical tool for predicting DGF. Additionally, IL-2 participates in the kidney injury process and may be a potential marker of kidney injury.

Identification of Subtypes and a Delayed Graft Function Predictive Signature Based on Ferroptosis in Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (IRI) is an inevitable process in kidney transplantation, leading to acute kidney injury, delayed graft function (DGF), and even graft loss. Ferroptosis is an iron-dependent regulated cell death in various diseases including IRI. We aimed to identify subtypes of renal IRI and construct a robust DGF predictive signature based on ferroptosis-related genes (FRGs). A consensus clustering analysis was applied to identify ferroptosis-associated subtypes of 203 renal IRI samples in the GSE43974 dataset. The FRG-associated DGF predictive signature was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO), and its robustness was further verified in the validation set GSE37838. The present study revealed two ferroptosis-related patient clusters (pBECN1 and pNF2 cluster) in renal IRI samples based on distinct expression patterns of BECN1 and NF2 gene clusters. Cluster pBECN1 was metabolically active and closely correlated with less DGF, while pNF2 was regarded as the metabolic exhausted subtype with higher incidence of DGF. Additionally, a six-gene (ATF3, SLC2A3, CXCL2, DDIT3, and ZFP36) ferroptosis-associated signature was constructed to predict occurrence of DGF in renal IRI patients and exhibited robust efficacy in both the training and validation sets. High-risk patients tended to have more infiltration of dendritic cells, macrophages, and T cells, and they had significantly enriched chemokine-related pathway, WNT/β-catenin signaling pathway, and allograft rejection. Patients with low risks of DGF were associated with ferroptosis-related pathways such as glutathione and fatty acid metabolism pathways. In conclusion, patient stratification with distinct metabolic activities based on ferroptosis may help distinguish patients who may respond to metabolic therapeutics. Moreover, the DGF predictive signature based on FRGs may guide advanced strategies toward prevention of DGF in the early stage.

Incidence Rate and Predictors of Delayed Graft Function Among Adult Kidney Transplant Recipients at a Tertiary Care Hospital in Riyadh, Saudi Arabia.

BackgroundDelayed graft function (DGF) is the most common early postoperative complication of renal transplantation. The occurrence of DGF can lead to both early and late devastating consequences on the allograft’s survival. The risk of developing this complication can increase with certain factors that are related to both the donor and the recipient. In the present study, we aimed to detect the incidence rate of DGF among patients attending a tertiary care hospital in Riyadh, Saudi Arabia, and to investigate potential predictors of DGF.Materials and methodsThis retrospective chart review was conducted at King Abdulaziz Medical City (KAMC), a tertiary care hospital in Riyadh, Saudi Arabia. The inclusion criteria were all patients, 18 years or older, who had renal transplantation from January 1, 2016, to March 31, 2020. Patients who had a second renal transplant, or renal transplantation in a different hospital and were followed up at KAMC were excluded. Patients’ medical records were accessed using the BESTCare electronic system to obtain the patients’ demographic data. A Chi-square test was used to test for the association between a predictor and a delay in graft function.ResultsA total of 344 patients were enrolled in the present study, approximately half of whom were males (56.6%, n=189). Around one-half (49.4%) were aged between 40 and 64 years. The most common cause of renal failure was hypertension, which was found in 117 (35%) patients, followed by diabetes mellitus (DM) in 94 (28.1%) patients. Most organ donors 258 (77.2%) were alive. A total of 23 (6.9%) participants developed DGF. Mycophenolate mofetil (MMF) was found to be significantly associated with DGF (P < 0.001). Those who took MMF (5.9%) had a significantly lower rate of DGF compared to those who did not (36.4%). A significantly higher rate of DGF was seen in patients whose transplants were taken from deceased donors (15.5%) compared to living donor transplants (3.9%). Gender, age, body mass index (BMI), recipient blood type, donor blood type, and cause of renal failure were not associated with DGF.ConclusionsOnly 6.9% of the study’s participants exhibited DGF. The observed rate was lower than the ones detected in the literature. Those who took MMF had a significantly lower rate of DGF compared to those who did not. Transplants of deceased donors (15.5%) showed a significantly higher rate of DGF. Larger multicenter studies are required to further investigate DGF in a region with a high prevalence of organ failure and a higher need for transplantations, such as Saudi Arabia.

A novel genomic model for predicting the likelihood of delayed graft function in DCD kidney transplantation.

BackgroundThe high incidence of delayed graft function (DGF) following kidney transplantation with donation after cardiac death allografts (DCD-KT) poses great challenges to transplant clinicians. This study aimed to explore the DGF-related biomarkers and establish a genomic model for DGF prediction specific to DCD KT.MethodsBy data mining a public dataset (GSE43974), the key DGF-related genes in DCD kidney biopsies taken after short-time reperfusion (45–60 min) were identified by differential expression analysis and a LASSO-penalized logistic regression model. Their coefficients for modeling were calculated by multivariate logistic regression. Receiver operating characteristic curves and a nomogram were generated to evaluate its predictive ability for DGF occurrence. Gene set enrichment analysis (GSEA) was performed to explore biological pathways underlying DGF in DCD KT.ResultsFive key DGF-related genes (CHST3, GOLPH3, ZBED5, AKR1C4, and ERRFI1) were first identified, all of which displayed good discrimination for DGF occurrence after DCD KT (all P<0.05). A five-mRNA-based risk score was further established and showed excellent predictive ability (AUC =0.9708, P<0.0001), which was obviously higher than that of the five genes alone. Eight DGF-related biological pathways in DCD kidneys, such as “arachidonic acid metabolism”, “lysosome”, “proximal tubule bicarbonate reclamation”, “glutathione metabolism”, were identified by GSEA (all P<0.05). Moreover, a convenient and visual nomogram based on the genomic risk score was also constructed and displayed high accuracy for DGF prediction specific to DCD KT.ConclusionsThe novel genomic model may effectively predict the likelihood of DGF immediately after DCD KT or even prior to transplantation in the context of normothermic machine perfusion in the future.

Activation of final complement components after kidney transplantation as a marker of delayed graft function severity

BackgroundIschaemia–reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients.MethodsWe evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies (n = 12) and a control group of 1-year protocol biopsies without tissue damage (n = 4) were stained for C5b-9, C3b and FH.ResultsSC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142 mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0–7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients.ConclusionsBoth SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.

Effects of mild hypothermia on serum HMGB1 of brain-dead donors and its impact on kidney transplantation recipients.

Investigate the effect of mild hypothermia on serum inflammatory factor HMGB1 of brain-dead donors, and its significance for renal transplantation recipients.In our hospital between January 2018 and January 2019 up to the standard of brain death donor (aged 18 to 65 years old) prospective cohort study, brain death donor were randomly divided into mild hypothermia group and the non-mild hypothermia group. Serum were collected from donor at different periods, and enzyme-linked immunoassay (ELISA) was used to determine the serum HMGB1 concentration to compare the difference between the 2 donor groups. The early recovery of renal function after renal transplantation was followed up, and the incidence of delayed graft function (DGF) and early recovery of renal function were compared between the 2 groups. The correlation between donor HMGB1 and recipient DGF was analyzed.Between 17 donors in the mild hypothermia group and 17 in the non-mild hypothermia group, there were no statistically significant differences in the age, perioperative urine volume and ICU stay between the 2 groups. After mild hypothermia treatment, serum HMGB1 levels of brain death donors were significantly decreased. While in non-mild hypothermia brain death donor group without treatment, serum HMGB1 was significantly increased. There were no statistically significant differences in age and preoperative creatinine between the 2 recipient groups, including 33 patients in the mild hypothermia group and 34 patients in the non-mild hypothermia group. DGF incidence was lower in mild hypothermia group comparing with non-mild hypothermia group with statistical significance. The levels of HMGB1 from donor before procurement is correlated with the occurrence of DGF of the recipient.Mild hypothermia therapy can reduce the levels of serum HMGB1, improve the function of donor organs. The levels of HMGB1 before donor procurement can be used to predict the occurrence of DGF in kidney transplant recipients. Our study shows that HMGB1 can be potentially used as therapeutic target of early intervention for brain death donors. Furthermore, mild hypothermia therapy can be applied in the maintenance of brain death donors for kidney transplant recipient to improve the successful rate of transplantation.

The impact of deceased donor maintenance on delayed kidney allograft function: A machine learning analysis.

This study evaluated the risk factors for delayed graft function (DGF) in a country where its incidence is high, detailing donor maintenance-related (DMR) variables and using machine learning (ML) methods beyond the traditional regression-based models. A total of 443 brain dead deceased donor kidney transplants (KT) from two Brazilian centers were retrospectively analyzed and the following DMR were evaluated using predictive modeling: arterial blood gas pH, serum sodium, blood glucose, urine output, mean arterial pressure, vasopressors use, and reversed cardiac arrest. Most patients (95.7%) received kidneys from standard criteria donors. The incidence of DGF was 53%. In multivariable logistic regression analysis, DMR variables did not impact on DGF occurrence. In post-hoc analysis including only KT with cold ischemia time<21h (n = 220), urine output in 24h prior to recovery surgery (OR = 0.639, 95%CI 0.444-0.919) and serum sodium (OR = 1.030, 95%CI 1.052-1.379) were risk factors for DGF. Using elastic net regularized regression model and ML analysis (decision tree, neural network and support vector machine), urine output and other DMR variables emerged as DGF predictors: mean arterial pressure, ≥ 1 or high dose vasopressors and blood glucose. Some DMR variables were associated with DGF, suggesting a potential impact of variables reflecting poor clinical and hemodynamic status on the incidence of DGF.

Comprehensive assessment of deceased donor kidneys with clinical characteristics, pre-implant biopsy histopathology and hypothermic mechanical perfusion parameters is highly predictive of delayed graft function

Background Due to the current high demand for transplant tissue, an increasing proportion of kidney donors are considered extended criteria donors, which results in a higher incidence of delayed graft function (DGF) in organ recipients. Therefore, it is important to fully investigate the risk factors of DGF, and establish a prediction system to assess donor kidney quality before transplantation. Methods A total of 333 donation after cardiac death kidney transplant recipients were included in this retrospective study. Both univariate and multivariate analyses were used to analyze the risk factors of DGF occurrence. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of variables on DGF posttransplant. Results The donor clinical scores, kidney histopathologic Remuzzi scores and hypothermic mechanical perfusion (HMP) parameters (flow and resistance index) were all correlated. 46 recipients developed DGF postoperatively, with an incidence of 13.8% (46/333). Multivariate logistic regression analysis of the kidney transplants revealed that the independent risk factors of DGF occurrence post-transplantation included donor score (OR = 1.12, 95% CI 1.06–1.19, p < 0.001), Remuzzi score (OR = 1.21, 95% CI 1.02–1.43, p = 0.029) and acute tubular injury (ATI) score (OR = 4.72, 95% CI 2.32–9.60, p < 0.001). Prediction of DGF with ROC curve showed that the area under the curve was increased to 0.89 when all variables (donor score, Remuzzi score, ATI score and HMP resistance index) were considered together. Conclusions Combination of donor clinical information, kidney pre-implant histopathology and HMP parameters provide a more accurate prediction of DGF occurrence post-transplantation than any of the measures alone.

Shorter Cold Ischemia Time in Deceased Donor Kidney Transplantation Reduces the Incidence of Delayed Graft Function Especially Among Highly Sensitized Patients and Kidneys From Older Donors

BackgroundLong cold ischemia time (CIT) is the most important factor contributing to delayed graft function (DGF) after kidney transplant. Improvements in pretransplant procedures may reduce CIT and improve clinical outcome. Materials and MethodsPretransplant histocompatibility tests were modernized at our laboratory in 2015, leading to significant decrease of time consumed for these enabling earlier surgery. The effects of this on kidney transplant CIT, DGF, and other clinical outcomes were studied. The study population consisted of 896 consecutive deceased donor kidney recipients, of which 442 patients received a transplant with the old crossmatch and 454 received a transplant with the new crossmatch. ResultsCIT shortened from mean 20 hours 6 minutes to 15 hours 52 minutes (P < .001). The incidence of DGF was significantly reduced from 31% to 24% (P = .02). Reduction in the frequency of DGF was more pronounced among the highly sensitized patients (53% to 28%, P = .01) or in patients with pretransplant donor-specific antibodies (50% to 20%, P = .002) and among patients who received kidneys from donors older than 65 years (38% to 27%, P = .04). ConclusionsProcess optimization that reduces CIT decreases occurrence of DGF, especially in highly sensitized patients and patients who receive kidneys from older donors.

Evaluation of outcomes in renal transplantation with hypothermic machine perfusion for the preservation of kidneys from expanded criteria donors.

In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011-2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One-year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR=0.49 [0.40-0.60]). Results were similar in the paired kidneys (OR=0.23 [0.04-0.57]). HMP use decreased risk for 1-year graft failure (HR=0.77 [0.60-0.99]). Initial hospital stays were shorter in the HMP group (P<0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP.

Long-term effects of delayed graft function duration on function and survival of deceased donor kidney transplants.

Introduction:Delayed graft function (DGF) is a frequent complication after deceased donor kidney transplantation with an impact on the prognosis of the transplant. Despite this, long-term impact of DGF on graft function after deceased donor kidney transplantation has not been properly evaluated.Objective:The main objective of this study was to evaluate risk factors for DGF and the impact of its occurrence and length on graft survival and function.Methods:A retrospective cohort study was performed in 517 kidney transplant recipients who received a deceased donor organ between January 2008 and December 2013.Results:The incidence of DGF was 69.3% and it was independently associated with donor's final serum creatinine and age, cold ischemia time, use of antibody induction therapy and recipient's diabetes mellitus. The occurrence of DGF was also associated with a higher incidence of Banff ≥ 1A grade acute rejection (P = 0.017), lower graft function up to six years after transplantation and lower death-censored graft survival at 1 and 5 years (P < 0.05). DGF period longer than 14 days was associated with higher incidence of death-censored graft loss (P = 0.038) and poorer graft function (P < 0.001). No differences were found in patient survival.Conclusions:The occurrence of DGF has a long-lasting detrimental impact on graft function and survival and this impact is even more pronounced when DGF lasts longer than two weeks.

A study of the main determinants of kidney allograft long-term survival in the era of new immunosuppressive drugs.

The outcome of long-term kidney allograft is extremely important. The present study aimed to discern the factors affecting long-term kidney allograft survival, including the type of donation and the use of extended criteria donors. Seven hundred and thirty-seven kidney transplant alone patients entered this retrospective cross-sectional study. The impact of different factors on death-censored long-term kidney allograft survival was evaluated. The Cox proportional survival model was employed to identify these factors. A value of P < 0.05 was considered statistically significant. The data were analyzed using IBM Statistical Package for the Social Sciences version 19.0. The study was conducted at the Mashhad University of Medical Sciences, Mashhad, Iran. In comparison with living kidney donations, both nontraumatic and traumatic brain death cadaveric kidney donations showed statistically significant inferior graft survival. Furthermore, the Kaplan-Meier survival analysis showed better durability of living kidney donations in comparison with traumatic and nontraumatic deceased donors (Log-rank test value = 0.001). Patients with delayed graft function (DGF) had a significantly shorter long-term death censured long-term graft survival in comparison with those without this complication. The Cox proportional models showed that DGF occurrence and the type of donation play a statistically significant role in long-term kidney graft survival. In addition, regarding graft survival, there was no difference between standard criteria and extended criteria donors. The occurrence of DGF and living or deceased types of donations have a significant effect on long-term kidney allograft survival.