Delayed Graft Function Research Articles

MiR-199a-5p aggravates renal ischemia-reperfusion and transplant injury by targeting AKAP1 to disrupt mitochondrial dynamics.

Renal ischemia-reperfusion injury (IRI) is a complex pathophysiological process and a major cause of delayed graft function (DGF) after transplantation. MicroRNA (miRNA) has important roles in the pathogenesis of IRI and may represent promising therapeutic targets for mitigating renal IRI. miRNA sequencing was performed to profile microRNA expression in mouse kidneys after cold storage and transplantation (CST). Lentivirus incorporating a miR-199a-5p modulator was injected into mouse kidney in situ before syngenetic transplantation and unilateral IRI to determine the effect of miR-199a-5p in vivo. miR-199a-5p mimic or inhibitor was transfected cultured tubular cells before ATP depletion recovery treatment to examine the role of miR-199a-5p in vitro. Sequencing data and microarray showed upregulation of miR-199a-5p in mice CST and human DGF samples. Lentivirus incorporating a miR-199a-5p mimic aggravated renal IRI, and protective effects were obtained with a miR-199a-5p inhibitor. Treatment with the miR-199a-5p inhibitor ameliorated graft function loss, tubular injury, and immune response after CST. In vitro experiments revealed exacerbation of mitochondria dysfunction upon ATP depletion and repletion model in the presence of the miR-199a-5p mimic, whereas dysfunction was attenuated when the miR-199a-5p inhibitor was applied. miR-199a-5p was shown to target A-kinase anchoring protein 1 (AKAP1) by double luciferase assay and miR-199a-5p activation reduced dynamin-related protein 1 (Drp1)-s637 phosphorylation and mitochondrial length. Overexpression of AKAP1 preserved Drp1-s637 phosphorylation and reduced mitochondrial fission. miR-199a-5p activation reduced AKAP1 expression, promoted Drp1-s637 dephosphorylation, aggravated the disruption of mitochondrial dynamics, and contributed to renal IRI.NEW & NOTEWORTHY This study identifies miR-199a-5p as a key regulator in renal ischemia-reperfusion injury through microRNA sequencing in mouse models and human delayed graft function. miR-199a-5p worsens renal IRI by aggravating graft dysfunction, tubular injury, and immune response, while its inhibition shows protective effects. miR-199a-5p downregulates A-kinase anchoring protein 1 (AKAP1), reducing dynamin-related protein 1 (Drp1)-s637 phosphorylation, increasing mitochondrial fission, and causing dysfunction. Targeting the miR-199a-5p/AKAP1/Drp1 axis offers therapeutic potential for renal IRI, as AKAP1 overexpression preserves mitochondrial integrity by maintaining Drp1-s637 phosphorylation.

Defining the molecular response to ischemia-reperfusion injury and remote ischemic preconditioning in human kidney transplantation

Background Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function and poor outcomes. Remote ischemic preconditioning (RIPC) is a simple, noninvasive procedure aimed at reducing IRI and improving graft function. Experimental studies have implicated the kynurenine pathway as a protective mechanism behind RIPC. Methods First, paired biopsies from 11 living kidney donors were analyzed to characterize the acute transcriptomic response to IRI. Second, 16 living kidney donors were subjected to either RIPC (n = 9) or no pretreatment (n = 7) to evaluate the impact of RIPC on the transcriptomic response to IRI. Finally, the effect of RIPC on plasma metabolites was analyzed in 49 healthy subjects. Results There was a robust immediate response to IRI in the renal transcriptomes of living-donor kidney transplantation, including activation of the mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) pathways. Preconditioning with RIPC did not significantly alter the transcriptomic response to IRI or the concentration of plasma metabolites. Conclusions The present data validate living-donor kidney transplantation as a suitable model for mechanistic studies of IRI in human kidneys. The failure of RIPC to alter transcriptomic responses or metabolites in the kynurenine pathway raises the question of the robustness of the standard procedure used to induce RIPC, and might explain the mixed results in clinical trials evaluating RIPC as a method to attenuate IRI.

Nuclear factor of activated T cell cytoplasmic 1 (NFATc1) insertion gene polymorphism as a possible trigger in acute T cell-mediated rejection (aTCMR) after kidney transplantation

BackgroundTo investigate the potential regulatory role of gene insertion or deletion (in/del) polymorphism in the occurrence of acute T cell-mediated rejection (aTCMR) after kidney transplantation. MethodsWe retrospectively analyzed the 5-year follow-up data of 133 recipients who underwent renal transplantation at the First Affiliated Hospital of Nanjing Medical University between February 1, 2010, and December 1, 2015. With target sequencing based on next-generation sequencing (NGS), tagger in/dels selection involved calculating the Hardy-Weinberg equilibrium (HWE), Minor Allele Frequency (MAF), and the linkage disequilibrium (LD) blocks. Significant in/dels associated with aTCMR were identified by intersecting the results obtained through analysis of covariance (ANCOVA) of clinical cofounders and model analysis in Rstudio using the “SNPassoc” package. Additionally, logistic models were employed to assess the associations between genotypes and the aTCMR occurrence in 5 years after surgery. ResultsNFATc1 rs55741427 insertion was identified to be significantly associated with the post-surgery aTCMR(OR = 2.66, P < 0.001). We constructed a conclusive model containing the occurrence of delayed graft function (DGF) and the insertion polymorphism of rs55741427, showing a favorable predictive ability (AUC = 0.766) for aTCMR after surgery. Based on the receiver operating characteristic (ROC) curve, all cases were stratified into aTCMR high-risk and low-risk groups. Kaplan-Meier curves for two groups revealed that the aTCMR high-risk group exhibited a more unfavorable graft survival outcome (P = 0.0048). ConclusionInsertion mutation of rs55741427 was found to be statistically correlated with the post-surgery aTCMR during 5 years of follow-up. Our model identified DGF and insertion of rs55741427 as two crucial aTCMR-related hazards, and aTCMR high-risk group showed a worse graft prognosis.

Normothermic Ex Vivo Perfusion Before Transplantation of the Kidney (NEXT-Kidney): A Single-center, Nonrandomized Feasibility Study.

There is conflicting evidence regarding the efficacy of normothermic machine perfusion (NMP) in suboptimal deceased donor kidneys. We aimed to assess the feasibility and short-term efficacy of brief preimplantation NMP in circulatory death (DCD) kidneys. In this nonrandomized, single-center, prospective clinical trial, DCD kidneys underwent 1 to 3 h of NMP before implantation, aiming to achieve short ischemic times off NMP. The primary outcomes included feasibility and safety. Secondary outcomes included efficacy outcomes (delayed graft function and estimated glomerular filtration rate (eGFR) at 1, 6, and 12 mo), which were compared with the contralateral kidney that did not receive NMP. Eighteen DCD kidneys underwent NMP between 2020 and 2022, with at least 1 h completed in 16 (88.9%) of these kidneys (median 1 h); one kidney was removed after 5 min because of cannula failure and another at 54 min because of a sudden drop in blood flows. There was no episode of graft loss on the machine or postoperative vascular thromboses. All 18 kidneys were transplanted, with no cases of PNF or graft loss at 12 mo. Seventeen of the contralateral CS kidneys were transplanted. Compared with the contralateral kidneys, a lower incidence of delayed graft function (23.5% versus 64.7%; P = 0.046) was observed. There were no differences in the eGFR slopes between the two groups over time (P = 0.254). NMP is safe, feasible and efficacious in the Australian setting, with this relatively small cohort demonstrating good early outcomes compared to CS alone in our study of DCD kidneys.

Overexpression of miR-451a Aggravates Renal Ischemia–Reperfusion Injury by Targeting KLF1-ACSL4 to Promote Ferroptosis

Ischemia–reperfusion injury (IRI) is a predominant factor leading to delayed graft function (DGF) following kidney transplantation. MicroRNAs (miRNAs) play a pivotal role in the pathogenesis of renal IRI, with ferroptosis being a critical driving force throughout the process. In this study, we utilized bioinformatics methods to construct a network diagram of differentially expressed miRNAs, transcription factors (TFs), and ferroptosis-related genes. An I/R-induced renal injury model in mice and an in vitro H/R-induced HK-2 cell injury model were established. Quantitative real-time PCR (qRT-PCR) and Western blot analysis were used to measure the mRNA and miRNA levels in cells and tissues. The MDA concentration, iron levels, and GSH concentration were measured to evaluate the ferroptosis levels. CCK-8 assays were performed to assess cell viability. Luciferase reporter assays were conducted to validate the downstream targets of miRNA, and chromatin immunoprecipitation assays were performed to verify the interaction between TFs and mRNAs. Both the in vivo and in vitro results demonstrate that miR-451a was significantly enriched in the IRI renal tissues and cells, exacerbating ferroptosis. MiR-451a was found to reduce the expression of Kruppel-like factor 1 (KLF1) by directly binding to the 3′UTR of KLF1 mRNA. Additionally, KLF1 was identified as a negative transcription factor for acyl-CoA synthetase long-chain family member 4 (ACSL4). We demonstrated that IRI induced the upregulation of miR-451a, which reduced KLF1 expression, thereby promoting ferroptosis by upregulating ACSL4 expression, ultimately aggravating IRI-induced renal damage.

Prospective study on immune function in renal transplant patients during perioperative period: A prospective cohort study.

Delayed graft function (DGF) is a type of acute renal failure that is closely linked to the immune system. The objective of this study is to investigate immune trends during the perioperative period of renal transplantation and compare the variations between patients with DGF and immediate graft function (IGF). A total of 48 kidney transplant patients were enrolled. Parameters including stimulated adenosine triphosphatase concentrations (sATP), nonstimulated ATP concentrations, white blood cells, and lymphocyte count were assessed. Patients were categorized into the DGF or IGF group. Clinical information and changes in immune markers were compared. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity in predicting DGF. Additionally, separate immune function analyses were conducted for the 3 infection cases. Following induction immunosuppressive therapy, white blood cells, and neutrophil count showed a significant initial increase followed by a gradual decline. Lymphocyte count, nonstimulated ATP concentrations, and sATP exhibited an initial significant decrease followed by a slow recovery. Immune markers between the DGF and IGF groups were significantly different at day 4 after renal transplantation. Only sATP levels at day 4 after renal transplantation (area under the curve = 0.731, sensitivity = 0.864, specificity = 0.684) demonstrated predictive value for DGF occurrence. Among the 3 infection cases, 2 cases exhibited persistently decreased sATP levels and died within the first month and 6 months, while the remaining case showed a recovery of sATP levels at D9 and survived. These findings indicate that sATP level can potentially serve as a biomarker reflecting the impact of immunosuppressants. Poor recovery of sATP may be associated with DGF, infection, or even mortality.

Intraoperative central venous pressures related to early graft function in deceased donor kidney transplant recipients with low immunological risks

This study aims to analyze data from patients who received kidney transplantation from deceased donors to investigate the anesthetic factors influencing early and late graft outcomes, including the incidence of slow graft function (SGF), delayed graft function (DGF), and 3-year graft outcomes. We retrospectively analyzed 202 recipients who underwent deceased donor kidney transplantation from March 2010 to December 2020. Anesthetic monitoring data during the intraoperative period was analyzed at 5-minute intervals, and basic clinical parameters were evaluated. The mean recipient age was 46.6 ± 10.3 years, and the mean donor age was 41.7 ± 12.7 years. Anesthetic time averaged 285.8 ± 70.2 min, and operation time averaged 223.1 ± 44.0 min. The incidence of SGF was 11.8%, and the incidence of DGF was 3.9%. Mean central venous pressures (CVPs) were higher in recipients with SGF or DGF (11.7 mmHg) compared to those with immediate graft function (9.7 mmHg). Higher CVP was identified as an independent risk factor for SGF or DGF (odds ratio 1.219, p = 0.006). This study suggests that intraoperative monitoring of CVP is crucial for predicting short-term graft function in deceased donor kidney transplantation and should be managed to prevent excessive fluid intake.

Promising Results of Kidney Transplantation From Donors Following Euthanasia During 10-Year Follow-Up: A Nationwide Cohort Study.

The outcome of kidneys transplanted following organ donation after euthanasia (ODE) remains unclear. This study analyzed all kidney transplantations in the Netherlands from January 2012 to December 2021, comparing the outcomes following ODE, donation after circulatory death (DCD-III), and donation after brain death (DBD). 9,208 kidney transplantations were performed: 148 ODE, 2118 DCD-III, and 1845 DBD. Initial graft function was compared between these categories. Immediate graft function, delayed graft function and primary non-function in ODE kidney recipients were 76%, 22%, and 2%, respectively, 47%, 50% and 3% in DCD-III kidney recipients and 73%, 25%, and 2% in DBD kidney recipients (overall p-value: p < 0.001). The number of kidneys transplanted over a median follow-up period of 4.0 years (IQR 2.0-6.6), was 1810, including 72 ODE, 958 DCD-III and 780 DBD kidneys. In this period, 213 grafts (11.8%) failed [7 grafts (9.7%) from ODE donors, 93 grafts (9.7%) from DCD-III donors, and 113 grafts (14.5%) from DBD donors]. Kidneys transplanted after euthanasia have a good immediate graft function, a comparable longitudinal 10years eGFR, and similar graft failure hazard to kidneys from DCD-III and DBD. Kidney transplantation following ODE is a valuable and safe contribution to the donor pool.

Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, deceased human recipient.

The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. We conducted a kidney xenotransplantation in a deceased human recipient using a porcine kidney with five gene edits (5GE) on March 25th, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.

A retrospective cohort analysis comparing the effectiveness and safety of perioperative angiotensin II to adrenergic vasopressors as a first-line vasopressor in kidney transplant recipients

BackgroundPerioperative adrenergic vasopressors in kidney transplantation have been linked to negative outcomes and arrhythmias. Synthetic angiotensin II (AT2S) could improve renal hemodynamics, preserve allograft function, and reduce arrhythmias.ObjectiveWe aimed to compare the effectiveness and safety of AT2S to adrenergic vasopressors when used for perioperative hypotension in kidney transplant.MethodsThis single-center, retrospective cohort study included adults with perioperative shock requiring AT2S or adrenergic agents as first-line vasopressors during kidney transplant. The primary outcome was the need for a second continuous infusion vasopressor agents beyond the first-line agent. Secondary outcomes assessed adverse events and early allograft outcomes.ResultsTwenty patients receiving AT2S and 60 patients receiving adrenergic vasopressor agents were included. Intraoperatively, 1 of 20 patients (5%) in the AT2S group needed a second continuous vasopressor compared to 7 of 60 patients (11.7%) who needed a second continuous vasopressor in the adrenergic vasopressor group (P = 0.672). Postoperatively, 1 of 20 patients (5%) in the AT2S group compared to 12 of 60 patients (20%) in the adrenergic vasopressor group required a second vasopressor (P = 0.168). There were significantly fewer arrhythmias (1/20 [5%] vs. 17/60 [28.3%]), P = 0.03) and ischemic complications (0/20 [0%] vs. 11/20 [18.3%], P = 0.031) in patients who received AT2S. There were no differences in immediate, slow, or delayed graft function or in discharge, 1-month, and 3-month glomerular filtration rates (p > 0.05).Conclusion and RelevanceBoth AT2S and adrenergic vasopressors are effective for perioperative hypotension in kidney transplant, with AT2S showing a lower incidence of arrhythmias and ischemic complications.

Basiliximab vs. No Induction Therapy in Kidney Transplant Recipients with a Low Immunological Risk Profile Receiving Tacrolimus/Mycophenolate/Steroids Maintenance Immunosuppression.

Background: Induction therapy with basiliximab is recommended in kidney transplant (KT) recipients with a low immunological risk (LIR) profile. Whether basiliximab is associated with a decreased risk of acute rejection (AR) and graft loss is controversial. Methods: In our institution, LIR patients (absence of anti-HLA antibodies before KT) are inducted with basiliximab in case of living-donor KT, while deceased-donor KT recipients receive no induction. Maintenance immunosuppression is similar, including a combination of tacrolimus (Tac), mycophenolate (MPA) and steroids. In this single-center retrospective study, we included all adult LIR patients who underwent KT between 1 January 2015 and 31 December 2022. Results: Of the 471 patients included, 354 received no induction and 117 received basiliximab. The median (IQR) number of HLA A-B-DR mismatches was 3 (2-3) and 2 (2-4) in the no induction group and the basiliximab group, respectively. The cumulative incidences in the no induction group vs. the basiliximab group of acute rejection and graft loss over 5 years post-KT were similar at 8.9% vs. 7.8% (p = 0.8) and 8.5% vs. 4.2% (p = 0.063), respectively. In multivariable Cox regression analysis, delayed graft function emerged as an independent risk factor for acute rejection (hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.23-6.13, p = 0.014) and graft loss (HR 9.32, CI 4.10-21.1, p < 0.001). Conclusions: Basiliximab did not provide any advantage in terms of rate of acute rejection and graft survival within 5 years post KT compared with a strategy without induction therapy in patients with a low immunological risk profile receiving triple maintenance immunosuppression Tac/MPA/steroids.

Ischemia‐Free Kidney Transplantation From Deceased Donor Kidneys: The First Retrospective Cohort Study

ABSTRACTBackgroundThe study aimed to evaluate the safety and effectiveness of ischemia‐free kidney transplantation (IFKT) in preventing ischemia‐reperfusion injury (IRI), a common complication associated with organ transplantation.MethodsTwelve kidneys were obtained from six donors and divided into two groups: the IFKT and the conventional kidney transplantation (CKT) group. The left kidneys underwent conventional cold perfusion and storage, while the right kidneys were procured using normothermic machine perfusion (NMP) to maintain uninterrupted blood supply. Perfusion parameters, metabolic and electrolyte parameters in the perfusate and urine, along with post‐transplant clinical data of the recipients, were collected for subsequent analysis.ResultsPerfusion flow rates varied from 100 to 300 mL/min under a pressure of 65 mmHg across different donor kidneys. Biochemical parameters such as the pH value, oxygen partial pressure, and electrolyte levels, including Na+ and K+ concentrations in the perfusate, remained stable within physiological ranges during NMP. Urine samples demonstrated significantly lower pH values, reduced Na+ concentrations, and elevated K+ concentrations compared to the perfusate, indicating effective kidney function in acid excretion, sodium retention, and potassium excretion during NMP. All patients survived, and the kidney grafts showed satisfactory function during the 12‐month follow‐up period. Clinical outcomes for recipients in the IFKT group were comparable to those in the CKT group, including similar rates of patient and graft survival at 1 year, as well as equivalent serum creatinine levels and eGFR at 1, 3, 6, and 12 post‐transplantation. Delayed graft function (DGF) occurred in one case (16.67%) from the same donor in both groups. One patient in the IFKT group experienced acute rejection, while no instances of primary graft nonfunction or other complications were observed in either group.ConclusionsOur findings indicate that the kidneys maintained in a physiological environment through NMP exhibit stable function, and post‐transplant allograft function is comparable between IFKT and CKT. The IFKT procedure demonstrates both feasibility and safety, presenting a promising approach to effectively mitigating IRI in kidney transplantation.

Does old-to-young kidney transplantation rejuvenate old donor kidneys?

The number of older organ donors is increasing due to the aging population. Aged kidneys often face problems such as delayed graft function but previous murine experiments suggested the possibilities of rejuvenation, for example, in a parabiosis setting between old and young mice. To investigate kidney-graft rejuvenation, we compared an old-to-young (O-Y) patient transplantation group and a transplantation group with donors/recipients of approx. the same age (SA) with the renal senescence marker p16 in kidney biopsy samples at baseline and one year post-transplantation. We retrospectively analyzed our hospital's 32 cases of living-donor ABO-compatible transplants performed between 2013-2020. Both the baseline and one-year biopsy (n=9) or only the baseline biopsy (n=32) were analyzed. We divided the nine cases into an O-Y group (donors' median age 68 yrs, recipients 41, difference -27) and an SA group (donors' median age 53 yrs, recipients 51.5, difference -3.5). p16 was stained with the clones JC8 and E6H4 to determine the precise p16-positive rate. The 32 baseline biopsies' p16-positive rate was weakly related to donor age, suggesting that the p16-positive rate can help evaluate kidney senescence. The (n=5) O-Y group's p16-positive rates were at baseline 0.08 and one year 0.12; the (n=4) SA group's rate was 0.03 at both baseline and one year. No kidney rejuvenation was observed, even when old donor kidneys went to young recipients.

Robotic kidney transplant has superior outcomes compared to open kidney transplant: results of a propensity match analysis.

Several studies have demonstrated the feasibility of robotic kidney transplant (RKT) as a safe alternative to open kidney transplant (OKT). However, significant selection bias in RKT patient selection limits meaningful comparison between the two techniques. This is a single-center retrospective review of a prospectively maintained kidney transplant database (2021-2024). Outcomes after the first 50 "non-selected" RKTs are compared with a contemporary cohort of 100 OKTs after propensity score matching for age, gender, BMI and type of donation (living vs deceased). Data pertinent to recipient demographics, intraoperative parameters, and short-term post-operative outcomes were collected and compared. Both groups were well-matched for recipient age, gender, BMI, and donation type. RKT group had significantly longer total operative time (RKT 258min vs. OKT 183min; p < 0.0001) and warm ischemia time (RKT 37min vs. OKT 31min; p < 0.0001) but significantly less blood loss (OKT 155ml vs. RKT 93ml). Average length of hospital stay for both groups was 5days, with OKT group demonstrating significantly higher rates of post-operative complications (OKT 31% vs. RKT 14%; p = 0.028), return to OR (OKT 15% vs. RKT 2%; p = 0.021), hematoma (OKT 13% vs. RKT 2%; p = 0.0355), and lymphocele (OKT 25% vs. RKT 6%; p = 0.0039). OKT group also had higher 30-day readmission rate (OKT 31% vs. RKT 14%) and post-operative opioid requirement (OKT 93 MME vs. RKT 65; p = 0.0254). There were no differences in rates of wound infection, urine leaks, delayed graft function, acute rejection, graft loss, and patient death between the two groups. RKT is a safe and viable alternative to OKT as a first-choice procedure for all patients with ESRD. RKT offers many advantages over OKT which can lead to its wider adoption in the coming years as the new standard of care for ESRD patients.

Delayed graft function has comparable associations with early outcomes in primary and repeat transplant among deceased-donor kidney transplant recipients.

Delayed graft function (DGF) is a common complication and is associated with worse outcomes among kidney transplant recipients (KTRs). There are various risk factors for DGF including previous transplant. We hypothesized that DGF among KTRs undergoing repeat transplant has a greater impact on outcomes compared to primary KTRs. All deceased-donor KTRs between 01/2000 and 12/2020 at our center were included. Recipients were categorized as primary KTR or repeat KTR (any number of previous kidney transplants). Outcomes of interest included acute rejection, death-censored graft failure, and patient mortality within 12months post-transplant. A total of 3137 deceased-donor KTRs were included; 2498(80%) were primary KTRs and 639(20%) were repeat KTRs. The rates of DGF were similar between the groups at 29% and 28%, respectively. Compared to KTRs without DGF, DGF was associated with a greater incidence of death and graft failure in both primary and repeat transplants; however, the risk of rejection was not significantly higher in repeat KTRs (p = 0.72). Comparing primary and repeat KTRs, there were no significant differences in either acute rejection (p-interaction = 0.11), death-censored graft failure (p-interaction = 0.38), or death (p-interaction = 0.37). In subgroup analysis among repeat KTRs with DGF, a repeat transplant with no prior DGF was associated with increased risk for death-censored graft failure and death but not for acute rejection. DGF in the prior transplant was protective against death-censored graft failure (HR: 0.07, 95% CI 0.005-0.98, p = 0.05) (p-interaction = 0.04), but this was not significantly associated with acute rejection or death. DGF is associated with similar detrimental outcomes among primary and repeat KTRs.

Delayed Graft Function among Simultaneous Pancreas-Kidney Transplant Recipients Is Associated with an Increased Risk of Urinary Tract Infections and Kidney Rejections

Delayed Graft Function among Simultaneous Pancreas-Kidney Transplant Recipients Is Associated with an Increased Risk of Urinary Tract Infections and Kidney Rejections

Features of Kidney Transplant in Pediatric Recipients: Experience of a Single Center.

Congenital abnormalities of the kidneys and the urinary tract are common reasons for endstage renal disease in children. We studied the features of postoperative management and possible complications after pediatric kidney transplant. We retrospectively analyzed 29 children aged from 9 to 18 years who underwent kidney transplants from April 2018 to December 2013 (17 boys and 12 girls). All recipients were on hemodialysis for 3 to 18 months (mean of 10.17 ± 4.52 mo). Etiology of end-stage kidney disease included chronic glomerulonephritis (n = 12 [41.4%]), urolithiasis (n = 3 [10.3%]), and congenital abnormalities of the kidneys and the urinary tract (n =14 [48.3%]), including urinary reflux (n = 5 [17.2%]). Donors were parents in 16 cases, siblings in 5, uncles in 5, and aunts in 3 cases. HLA mismatching ranged from 2 to 5 (mean of 2.93 ± 1.39). Three patients had intraoperative nephrectomy, and 2 patients had hydronephrosis and urethroplasty with megaureter to prevent urinary tract infection. Six patients (20.6%) had early postoperative complications: 2 with delayed graft function, 1 with venous anastomosis thrombosis, 2 with hematoma around the graft, and 1 with lymphocele. Venous anastomosis thrombosis was eliminated by open thrombectomy, with graft function restored on postoperative day 17. The lymphocele was eliminated by puncture and drainage. Hematomas did not require surgical correction and blood transfusion. Ten patients (34.4%) had late postoperative complications: 1 with stricture of vesicoureteral anastomosis, 3 with vesicoureteral reflux, and 5 with urinary tract infection (3 with bacterial culture). Stricture of vesicoureteral anastomosis was successfully resolved by open surgery. Vesicoureteral reflux was eliminated with hydrogel. One patient developed chronic kidney rejection within 6 months because of noncompliance with posttransplant regimen and required transplantectomy. A major factor in reducing frequency of infections after surgery is the recipient's nephrectomy.

Association of Intraoperative Hypotension With Delayed Graft Function Following Kidney Transplant: A Single Centre Retrospective Cohort Study.

Intraoperative hypotension is associated with acute kidney injury after surgery. However, the definition (duration and magnitude) of hypotension during kidney transplantation (KT) surgery on early graft function remains unclear. We conducted a retrospective cohort study of KT recipients from December 1, 2009, to December 31, 2019. Exposure to intraoperative hypotension was characterized as the duration (minutes) of mean arterial pressure (MAP) <55, <65, <75, and <85mmHg. Our co-primary outcomes were DGF-creatinine reduction ratio (DGF-CRR, <30% creatinine reduction, postoperative days 1 and 2), and DGF-dialysis (DGF-D, required dialysis within the week of KT for deceased donor recipients). Logistic regression models were fitted to assess this relationship between MAP and DGF. We included 1602 KT (939 deceased donors, 663 living donors) and 23 were excluded. DGF-CRR occurred in 33% of patients. DGF-CRR was associated with MAP<65 (>5min: OR 1.77, 95% confidence interval [CI]: 1.39-2.30; 6-10min: OR 1.67, 95% CI: 0.97-2.86; 11-20min: OR 2.18, 95% CI: 1.31-3.63) in unadjusted and <55mmHg (5 min: OR 1.85, 95% CI: 1.47-2.32; 5-10min: OR 2.41, 95% CI: 1.65-3.53; 11-20min: OR 2.36, 95% CI: 1.60, 3.48) in adjusted models. There was also a signal for increased risk of DGF-CRR at MAP<75 (>5min: OR 1.69, 95% CI: 1.02-2.80). DGF-D (incidence 35%) in deceased donor KT was not associated with hypotension. We found an association between intraoperative hypotension and DGF-CRR at a threshold MAP of 55mmHg, with a consistent signal toward increased risk at both 65 and 75mmHg, as indicated by unadjusted models.

Markers for Cell Death and Purine Metabolites in Patients with and without Delayed Graft Function after Kidney Transplantation

Markers for Cell Death and Purine Metabolites in Patients with and without Delayed Graft Function after Kidney Transplantation

Time Course Analysis of Serial Biopsies Post-Kidney Transplant Reveals a Time Zero Cell State Negatively Associated with Delayed Graft Function

Time Course Analysis of Serial Biopsies Post-Kidney Transplant Reveals a Time Zero Cell State Negatively Associated with Delayed Graft Function