Delayed Graft Function Research Articles

Does Normothermic Machine Perfusion Still Provide an Advantage for Deceased Donor Kidney Transplantation? A Systematic Review and Preliminary Meta-Analysis.

Patients with end-stage renal disease often face prolonged waiting times for kidney transplants. Historically, the use of marginal kidneys was limited due to suboptimal preservation methods. Normothermic machine perfusion (NMP) preserves physiological activity during the preservation process, potentially improving graft function and viability, expanding the use of marginal kidneys. While preliminary results are promising, NMP has not yet undergone sufficient clinical trials to determine whether it offers advantages over more widely used techniques. The aim of this systematic review is to assess several outcomes between kidneys that underwent NMP compared to traditional preservation methods after kidney transplant. A systematic review was conducted following PRISMA guidelines. Randomized controlled trials, case series, and studies comparing NMP with hypothermic machine perfusion (HMP) or static cold storage (SCS) were included. The primary outcome assessed was delayed graft function (DGF). Secondary outcomes included primary non-function (PNF), acute rejection, and 1-year graft survival. Eight NMP studies met the inclusion criteria. Meta-analysis showed significant differences in DGF between NMP and control (HMP or SCS) groups (OR: 0.47 [0.22, 0.99], p < 0.05). There were no significant differences between NMP and controls for PNF, acute rejection, or 1-year graft survival. These findings suggest that NMP yields similar adverse outcome rates compared to traditional methods. Notably, NMP could be associated with reduced rates of DGF. While NMP is a promising technique for renal allograft preservation, further randomized controlled trials are necessary to definitively establish its benefits over conventional preservation methods.

Impact of Race on Transplantation in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end-stage kidney disease (ESKD) and occurs without racial predilection. In general, non-White ESKD patients have less access to transplantation, especially living donor transplantation. We examined long-term outcomes of ADPKD-ESKD patients by self-reported race, with attention to the trajectory of Estimated Post-Transplant Survival (EPTS) scores over time. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify 32,611 ADPKD transplant recipients between 1/2000-12/2022. EPTS scores were calculated from the date of waitlisting until transplantation occurred. Cumulative incidences of living and deceased transplantation were calculated and plotted. Cox models were made for graft failure and death, and a sub-distribution hazards model for graft failure accounted for death as a competing outcome, with adjustment for patient, donor, and transplant factors. Compared to White ADPKD patients, all other groups had more dialysis years, more delayed graft function, and fewer living and pre-emptive transplants; mean EPTS scores were lower in African American (AA) and Hispanic patients at each timepoint on the waitlist. However, EPTS scores at the time of transplant was less likely to be <20% in AA and Hispanic patients, due to longer waiting time. AA patients had a significantly higher risk of graft failure with death as competing risk compared to White patients. Asian and Hispanic patients had similar graft survivals but better patient survival compared to White patients. Waitlist experience, allograft quality, and post-transplant outcomes of patients with ADPKD are influenced by patient race.

Long Term Outcomes of Transplant Recipients Comparing Belatacept vs. Tacrolimus: A UNOS Database Analysis.

Calcineurin inhibitors have been the choice for maintenance immunosuppression (IS) in kidney transplant recipients (KTR), but they are associated with nephrotoxicity and metabolic side effects. We aim to compare the long-term outcomes of KTR on belatacept (bela) versus tacrolimus (tac) IS, in all KTRs and various subgroups. Using the UNOS-STAR files, we identified adult first-KTR from 2010 to 2022. Patients were categorized based on maintenance-IS at index transplant admission by creating a propensity score matched cohort at 1:5 rate using several clinical characteristics. Primary outcomes included patient death, graft failure (GF), and death-censored graft failure (DCGF). Secondary outcomes included delayed graft function (DGF), acute-rejections (AR) within a year, and serum creatinine (Cr) at 1-year. The propensity-matched cohort included KTRs on bela (N = 2612) and tac (N = 12760). There was no significant difference in the hazard ratio of death (1.03 [0.92, 1.14]), GF (1.07 [0.97, 1.17]), or DCGF (1.11 [0.98, 1.25]). A sensitivity analysis comparing a propensity-matched cohort of bela+tac (n = 2033) versus tac (n = 9004); demonstrated significantly reduced risks of death (0.87 [0.76-1.00], p = 0.043) and GF (0.73 [0.64-0.83] p < 0.001) compared to those on Tac alone. In conclusion, bela+tac seems to be a nephron-sparing and rejection-lowering IS regimen with overall improved graft and patient outcomes when compared to the current standard of tacrolimus. Larger Randomized Controlled studies are needed.

Short (2-Hour) Non-Oxygenated End-Ischemic Hypothermic Perfusion Versus Cold Storage in the Setting of Renal Transplantation.

Kidney transplantation (KT) is the most effective treatment for end-stage renal disease. End-ischemic hypothermic machine perfusion (EI-HMP) has emerged as a promising method for preserving grafts before transplantation. This study aimed to compare graft function recovery in KT recipients of deceased brain-death (DBD) grafts preserved with EI-HMP versus static cold storage (SCS). The primary outcome was the rate of delayed graft function (DGF). Secondary outcomes included urine output, intensive care unit (ICU) stay, hospital stay duration, and survival rates. A retrospective, single-center observational study was conducted at Sapienza University of Rome, analyzing 313 KT patients between January 2014 and September 2021. Patients were stratified into two groups based on graft preservation methods (EI-HMP, n = 95; SCS, n = 218). A stabilized inverse probability treatment weighting (IPTW) method was employed to adjust for potential confounders. There were no significant differences in DGF rates between the two groups (17.9% vs. 15.6% in SCS and EI-HMP cases, respectively; p = 0.75). EI-HMP group demonstrated a higher urine output on day 2 (p = 0.046), a shorter ICU stay (p < 0.0001), and a trend toward a shorter overall hospital stay (p = 0.07). No statistically significant differences were found between EI-HMP and SCS cases in 1- and 3-year overall survival rates (3.2% and 6.7% vs. 5.6% and 6.6%, respectively; log-rank p = 0.53) or in death-censored graft loss rates (5.4% and 8.9% vs. 5.7% and 7.3%, respectively; log-rank p = 0.88). In a sub-analysis of expanded criteria donors (ECD), EI-HMP demonstrated a protective effect by reducing the risk of DGF (OR = 0.31, 95% CI = 0.09-0.95; p = 0.047). EI-HMP was associated with certain short-term benefits, including increased urine output and reduced ICU stays, but showed no significant impact on long-term survival outcomes. A reduction in DGF rates was observed only in the ECD subgroup. Randomized controlled trials are necessary to further investigate the long-term clinical benefits of EI-HMP.

The Landscape of Hepatitis C Virus Infection in Pediatric Kidney Transplantation.

Hepatitis C virus (HCV) infection is increasing in prevalence due to the growing opioid epidemic; however, its impact on pediatric kidney transplantation is unknown. This study compared kidney transplant outcomes between HCV-positive and propensity-score-weighted HCV-negative pediatric recipients. It also examined HCV-positive kidney utilization for pediatric transplantation in the United States. We used the Scientific Registry of Transplant Recipients to identify pediatric kidney transplants (<18 years) performed between 4/1/1994 and 12/1/2022. We used propensity-score weighting to create a group of HCV-negative recipients with characteristics similar to HCV-positive recipients. Odds ratios (OR) for delayed graft function (DGF) and hazard ratios (HR) for patient and graft survival were estimated using logistic and Cox regression models. We found similar DGF rates (13.9% vs. 10.3%, p=0.14) and no difference in graft (HR: 1.04, 95% CI: 0.83-1.31, p=0.71; 10-year survival 54.9% vs. 54.5%) or patient survival (HR: 1.06, 95% CI: 0.58-1.95, p=0.84; 10-year survival 93.9% vs. 92.0%) between the groups. Four HCV-positive (2.5%), 3 HCV-negative children (0.02%), and 1 (0.05%) child with unknown HCV status received HCV-positive kidneys. We observed no increased risk of graft loss or death in children with HCV infection. The use of HCV-positive donors for pediatric kidney transplantation is rare.

Factors Impacting Early Adverse Outcomes in Simultaneous Heart-Kidney Transplantation.

Over the last decade, the number of simultaneous heart-kidney transplants (SHKTs) has increased dramatically. There are few reports of renal allograft outcomes in these high acuity patients. The goal of the present study was to identify variables that were related to early adverse outcomes (EAOs), including delayed graft function (DGF), primary non-function (PNF), and renal allograft futility (RAF) after SHKTs. We performed a single center retrospective review of all adults undergoing SHKTs from October 2011 to August 2021. Multivariable logistic regression models with backward elimination were used to test the relationships between recipient (pre-transplant dialysis, intra-aortic balloon pump, serum lactate, norepinephrine use, and re-do sternotomy) and operative (cold ischemia time [CIT]) variables and the likelihood of DGF, PNF, and RAF. Sixty-eight patients underwent SHKT during the study period. Overall, patient survival was 87%, 83%, and 80% at 6 months, 1 year, and 3 years, respectively. Twenty-four patients (35%) experienced DGF, whereas 4 patients (6%) had PNF, and 12 patients (18%) had RAF (Table 1). Pre-transplant dialysis, serum lactate, and CIT were significantly associated with an increased likelihood of DGF. Norepinephrine (NE) and CIT were associated with increased likelihood of RAF (Table 2). Pre-transplant dialysis is related to an increased likelihood of EAO following SHKT, with CIT and NE contributing to increased likelihood of RAF. Given that SHKT recipients are at risk of remaining on dialysis following SHKT, strategies that allow for expedited kidney transplantation after heart transplantation may mitigate the hemodynamic and ischemic constraints of SHKT that contribute to early adverse outcomes.

The relationship between surgical difficulty and postoperative complications in kidney transplantation: establishment of a preoperative prediction model.

Introduction This study aims to investigate the relationship between surgical difficulty and postoperative complications in kidney transplantation, as well as to develop a preoperative prediction model for assessing surgical difficulty. Methods This is a prospective cohort included 122 kidney transplant adult recipients. The subjective score for operative difficulty, ranging from 1 to 3 points, served as the quantitative measure of surgical difficulty. Analysis of Variance (ANOVA) and Chi-square tests were employed to investigate the differences in postoperative complications. Additionally, Pearson and Spearman correlation analyses were conducted to assess the relationship between preoperative data and surgical difficulty scores, while multiple linear regression analysis was utilized to develop a prediction model. Results With the increase of surgical difficulty, the incidence and severity of postoperative complications of kidney transplant recipients increased significantly (1 vs 2, P=0.009; 1 vs 3, P=0.004; 2 vs 3, P=0.004). The incidence of delayed graft function (DGF) and graft loss was relatively high(1 vs 2, P<0.001; 1 vs 3, P<0.001; 2 vs 3, P=0.131). The source of donor kidney, number of arteries after donor kidney trimming, end resistance index of in vitro perfusion, vascular anastomosis mode of recipient, BMI, and calcification of the vessels to be anastomosed were influencing factors of surgical difficulty. The results of linear regression analysis showed that the difficulty of surgery =0.30 (donated by relatives) +0.48× the number of arteries +0.58× end resistance index of isolated perfusion +0.24× the mode of arterial anastomosis+0.02×BMI+0.17 (calcification of the vessel). Conclusion Higher levels of difficulty in kidney transplantation are associated with increased incidence and severity of postoperative complications, as well as prolonged recovery times. Concurrently, we developed a predictive model to quantify the difficulty of kidney transplantation and validated its accuracy.

Assessing donor kidney function: the role of CIRBP in predicting delayed graft function post-transplant

Assessing donor kidney function: the role of CIRBP in predicting delayed graft function post-transplant

Bibliometric study and visual analysis of postoperative diabetes mellitus in kidney transplant recipients based on WoSCC database

Background In recent years, the increase of the post-transplantation diabetes mellitus (PTDM) after renal transplantation encourages people to do a lot of research on the disease. This paper conducted a bibliometric study on PTDM related literature to explore the risk factors of diabetes after kidney transplantation, as well as the current status, hotspots and development trends of PTDM research, so as to provide reference for researchers in related fields. Methods We searched the Web of Science Core Collection (WoSCC) database for PTDM literature from January 1, 1990, to August 20, 2023, and used VOSviewer, CiteSpace, and the R package ‘bibliometrix’ to do bibliometric analysis. Results Obesity, 3 months after transplantation tacrolimus concentration >10 ng/mL, temporary hyperglycemia, delayed graft function, acute rejection is specific risk factors related to PTDM in renal transplant recipients. In addition, 74 countries led by China and the United States published 1546 papers, and the number of PTDM-related publications is increasing every year. Primary institutions included the University of California, Los Angeles, Mayo Clinic, University of Oslo, and University of Toronto. The Journal of Transplantation is the most widely read journal in the subject. The authors with the most published literature are Trond Jenssen and Adnan Sharif, and the most cited author is Kasiske BL. Expectations for continued growth in global PTDM research are increasingly high. Future studies will mainly focus on exploring the risk factors of PTDM and identifying new therapeutic approaches and targets.

Exploring Potential Complement Modulation Strategies for Ischemia-Reperfusion Injury in Kidney Transplantation.

The complement system plays a crucial role in regulating the inflammatory responses in kidney transplantation, potentially contributing to early decline in kidney function. Ischemia-reperfusion injury (IRI) is among the factors affecting graft outcomes and a primary contributor to delayed graft function. Complement activation, particularly the alternative pathway, participates in the pathogenesis of IRI, involving all kidney compartments. In particular, tubular epithelial cells often acquire a dysfunctional phenotype that can exacerbate complement activation and kidney damage. Currently, complement-modulating drugs are under investigation for the treatment of kidney diseases. Many of these drugs have shown potential therapeutic benefits, but no effective clinical treatments for renal IRI have been identified yet. In this review, we will explore drugs that target complement factors, complement receptors, and regulatory proteins, aiming to highlight their potential value in improving the management of renal IRI.

Only IF/TA in the Histological Evaluation of Post-Reperfusion Baseline Biopsies Correlates With Kidney Transplant Outcome.

Here, we retrospectively evaluated the informational yield of 338 post-reperfusion kidney transplant biopsies (including 95 living donations) assessed according to BANFF for the histological characteristics interstitial fibrosis and tubular atrophy (IF/TA), glomerulosclerosis, arteriosclerosis, and acute tubular injury (ATI). Associations with delayed graft function (DGF) and death-censored graft survival were explored through Cox-regression analyses. The maximum follow-up time was 11.4 years, with DGF observed in 108 (32%) cases. After deceased donation there was no association between DGF and histologic parameters. Univariable Cox-regression unveiled an association of IF/TA and glomerulosclerosis with long-term death-censored graft survival (HR per 10% increase: IF/TA 1.63; 95% CI 1.17-2.28; p = 0.003; glomerulosclerosis 1.19; 95% CI 1.01-1.39; p = 0.031). In multivariable Cox regression analyses, adjusted for recognized clinical risk variables like expanded criteria donor-status, donor age, history of diabetes, and HLA-mismatches, only IF/TA maintained association over the total observation period in deceased donations and in the total cohort. Arteriosclerosis and ATI were not associated with clinical outcome after deceased donation. Especially ATI did not affect delayed graft function if only deceased donations were considered. Our data underlines the role of organ quality for transplant outcome prior to acute lesions such as ATI during the transplantation process.

High Atherogenic Index of Plasma Associated With Delayed Graft Function in Living Donor Renal Transplant Recipients: A Single-Center Study in Vietnam.

To determine the predictive value of the atherogenic index of plasma before transplant for delayed graft function. A cross-sectional, longitudinal, non-interventional, non-controlled study of 167 patients undergoing kidney transplantation from living donors, with a mean age of 39.34 ± 11.86 years old, 53.3% male, and a pre-transplant hemodialysis time of 14 (7-36) months. Delayed graft function was defined as decreased blood creatinine < 25% within the first 24 h compared to pre-transplantation, and the patients needed hemodialysis in the first 7 days. The atherogenic index of plasma was calculated based on pre-transplant plasma triglycerides and high-density lipoprotein cholesterol concentrations. The ratio of delayed graft function in renal transplant recipients from living donors was 13.8% (23/167 patients). Hemodialysis time, the ratio of hepatitis infection, overweight and obese, atherosclerosis, positive PRA, and acute rejection in the DGF (+) group were higher than those of the DGF (-) group, p < 0.05 and < 0.001. In particular, plasma CRP-hs level and AIP also were higher in DGF (+) patients compared to those of DGF (-) ones, p < 0.001. Long hemodialysis time, obesity, high plasma CRP-hs, and high AIP in pre-transplant patients were independent factors related to DGF and had predictive value for DGF after kidney transplantation, in which AIP had good predictive value: AUC = 0.859, p < 0.001. Delayed graft function was relatively common in renal transplant recipients from living donors. AIP before kidney transplant was a good predictor for delayed graft function.

Balanced Electrolyte Solutions Versus 0.9% Saline for Kidney Transplantation: An Updated Systematic Review and Meta-analysis.

Perioperative intravenous fluids are administered to kidney transplant recipients to maintain hemodynamic stability and graft perfusion; however, the ideal fluid remains uncertain. Although 0.9% saline (saline) is commonly used, its high chloride content causes hyperchloremic metabolic acidosis and may increase the risks of delayed graft function (DGF) and hyperkalemia. Balanced electrolyte solutions (BES) have a more physiological chloride concentration and may reduce these risks. Previous meta-analyses found insufficient evidence to compare BES with saline for these outcomes; however, new studies have recently been published. In this updated review, we compared the effects of BES with saline on the risk of DGF and hyperkalemia in kidney transplantation. MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials comparing BES with saline in kidney transplantation. The primary outcomes were DGF and hyperkalemia. Eligible studies were assessed for risk of bias and data were pooled for analysis. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess the quality of evidence. Ten studies involving 1532 participants were included. The quality of evidence was high for deceased donor transplantation and very low for living donor transplantation. The relative risk (RR) of DGF associated with BES compared with saline was 0.83 (95% confidence interval [CI], 0.71-0.96; P = 0.01) in deceased donor transplantation. There was no difference in DGF in living donor transplantation (RR 0.79; 95% CI, 0.26-2.41; P = 0.68). There was no difference in hyperkalemia between groups (RR 0.87; 95% CI, 0.59-1.27; P = 0.46). Compared with saline, BES reduces the risk of DGF in deceased donor kidney transplantation without increasing hyperkalemia.

Syndecan-1 in the Serum of Deceased Kidney Donors as a Potential Biomarker of Kidney Function.

The process of kidney transplantation remains the optimal treatment for end-stage renal disease, offering improved quality of life and increased survival rates compared to long-term dialysis. However, despite advances in surgical techniques, immunosuppression regimens, and post-operative care, there are still significant challenges in predicting the organ's status and long-term outcomes of transplantation. Among the many factors that influence graft survival, the quality of the donated organ plays a fundamental role. There is an ongoing need for accurate and reliable biomarkers. Syndecan-1 is found in the endothelial glycocalyx and shed at a higher rate into the blood during systemic pathological conditions. The aim of this study is to evaluate the potential of serum syndecan-1 levels as a biomarker for assessing donor kidney quality and to investigate its correlation with donor characteristics and short-term outcomes in kidney recipients. We investigated serum syndecan-1 levels in 80 deceased donors and correlated them with donor characteristics and short-term outcomes (defined as delayed graft function - defined as the need for dialysis within the first week post-transplantation and renal function at 3 months post-transplantation - assessed using serum creatinine levels) in 104 corresponding kidney recipients. This single-center retrospective observational cohort study was conducted from April to December 2021. The donor pool consisted of 65% males with a median age of 53 years. Of these, 45 donors (56%) were classified as extended criteria donors. Higher syndecan-1 levels correlated with the last creatinine levels before organ procurement (R = 0.32, p = 0.01) and were marginally higher in donors with acute kidney injury (p = 0.07). However, syndecan-1 levels were not associated with short-term outcomes in kidney recipients (renal function at 3 months). The data suggests syndecan-1 could be a potential biomarker for assessing donor kidney quality, although its implications on recipient outcomes require further study. This pilot investigation underscores the importance of syndecan-1 in evaluating organ quality but highlights the necessity for more extensive research to validate these findings and explore their implications in transplant success.

Short Term Use of Belatacept in Kidney Transplant Recipients with Delayed Graft Function

Short Term Use of Belatacept in Kidney Transplant Recipients with Delayed Graft Function

Delayed Graft Function After Kidney Transplant Is Comparable Between Donation After Brain Death and Donation After Normothermic Regional Perfusion

Delayed Graft Function After Kidney Transplant Is Comparable Between Donation After Brain Death and Donation After Normothermic Regional Perfusion

Tailoring Kidney Transplant Strategies: Unraveling the Impact of Acute Kidney Injury and Preservation Methods Across Different Strata of Kidney Risk.

The use of donor kidneys with acute kidney injury (AKI) aims to expand the organ pool, but uncertainty remains regarding their outcomes across different Kidney Donor Profile Index (KDPI) groups and preservation methods. We retrospectively analyzed 108160 deceased donor kidney transplants from the OPTN database, focusing on adult recipients of kidneys from donors with or without AKI between December 2014 and December 2022. Propensity matching was used for each KDPI group (1-20, 21-59, 60-84, and 85-100), comparing donors with AKIN stages 0-1 to AKIN stages 2-3. Cox proportional hazards analysis assessed graft survival by AKIN stages and preservation type. The use of AKIN stage 2-3 kidneys significantly increased over the study period. AKIN does not negatively impact graft survival in the KDPI 1-20 group and is linked to improved survival in KDPI 21-59 and 60-84. In the KDPI 85-100 group, AKIN stage 2-3 shows a trend toward increased graft failure. Pump preservation reduces delayed graft function (DGF) across most KDPI groups but does not consistently improve long-term survival, except in KDPI 85-100. Transplantation with AKIN stage 2-3 kidneys is viable, but outcomes vary by KDPI group. Tailored guidelines should consider transplant center capabilities.

Uncovering the Mechanisms of Delayed Graft Function (DGF) in Human Kidney Transplants Using Single-Cell Spatial Transcriptomics

Uncovering the Mechanisms of Delayed Graft Function (DGF) in Human Kidney Transplants Using Single-Cell Spatial Transcriptomics

Hypothermic Oxygenated Machine Perfusion Reduces Delayed Graft Function in Kidney Transplantation at a Single U.S. Center

Hypothermic Oxygenated Machine Perfusion Reduces Delayed Graft Function in Kidney Transplantation at a Single U.S. Center

The impact of donor diabetes on recipient postoperative complications, renal function, and survival rate in deceased donor kidney transplantation: a single-center analysis

As the global incidence of diabetes rises and diagnoses among younger patients increase, transplant centers worldwide are encountering more organ donors with diabetes. This study examined 80 donors and 160 recipients, including 30 donors with diabetes (DD) and their 60 recipients (DDR). The control group comprised 50 non-diabetic donors (ND) and 100 recipients (NDR). We analyzed clinical, biochemical, and pathological data for both diabetic and control groups, using logistic regression to identify risk factors for delayed graft function (DGF) after kidney transplantation. Results showed that pre-procurement blood urea nitrogen levels were significantly higher in DD [18.20 ± 10.63 vs. 10.86 ± 6.92, p = 0.002] compared to ND. Renal pathological damage in DD was notably more severe, likely contributing to the higher DGF incidence in DDR compared to NDR. Although DDR had poorer renal function during the first three months post-transplant, both groups showed similar renal function thereafter. No significant differences were observed in 1-year or 3-year mortality rates or graft failure rates between DDR and NDR. Notably, according to the Renal Pathology Society (RPS) grading system, kidneys from diabetic donors with a grade > IIb are associated with significantly lower postoperative survival rates. Recipient gender [OR: 5.452 (1.330–22.353), p = 0.013] and pre-transplant PRA positivity [OR: 34.879 (7.698–158.030), p < 0.001] were identified as independent predictors of DGF in DDR. In conclusion, transplant centers may consider utilizing kidneys from diabetic donors, provided they are evaluated pathologically, without adversely impacting recipient survival and graft failure rates.