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Evaluation of hyperbranched polyglycerol for cold perfusion and storage of donor kidneys in a pig model of kidney autotransplantation.

ABSTRACT: Hyperbranched polyglycerol (HPG) is a biocompatible polyether polymer that is a potential colloid component in a preservation solution for suppressing interstitial edema during cold storage of a donor organ. This study evaluated the outcomes of kidney transplants after cold perfusion and storage with a HPG-based preservation solution (HPGS) in a pig model of kidney autotransplantation. The left kidneys of farm pigs (weighing 35-45 kg) were perfused with and stored in either cold HPGS or standard UW solution (UWS), followed by transplantation to the right side after right nephrectomy. The survival and function of transplants were determined by the urine output, and serum creatinine (SCr) and blood urea nitrogen (BUN) of recipients. Transplant injury was examined by histological analysis. Here, we showed that there was no significant difference between HPGS and UWS in the prevention of tissue edema, but HPGS was more effective than UWS for initial blood washout of kidney perfusion and for the prevention of cold ischemia injury during cold storage. After autotransplantation, the kidneys preserved with HPGS (HPG group) had better functional recovery than those with UWS (UW group), indicated by significantly more urine output and lower levels of SCr and BUN. The survived grafts in HPG group had less tissue damage than those in UW group. In conclusion, as compared to the UWS the HPGS has less negative impact on kidney cold ischemia during cold storage, resulting in improving immediate functional recovery after transplantation, suggesting that HPG is a promising colloid for donor kidney preservation.

SUBMITTER: Li S

PROVIDER: S-EPMC8246781 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Transcriptomic analysis of Kidney Machine normothermic perfusion and comparision to cold storage

Project description:Kidneys which had been taken for transplant but later declined were perfused for up to 4 hours using a normothermic perfusion (MNP) rig or left on ice (CS) and samples were taken for RNASeq at different time points. The effect of the addition of a heamoadsorber (HA) to the perfusion rig was also assessed.

2020-10-17 | GSE121447 | GEO

Machine perfusion versus cold storage of kidneys derived from donation after cardiac death: a meta-analysis.

Project description:BackgroundIn response to the increased organ shortage, organs derived from donation after cardiac death (DCD) donors are becoming an acceptable option once again for clinical use in transplantation. However, transplant outcomes in cases where DCD organs are used are not as favorable as those from donation after brain death or living donors. Different methods of organ preservation are a key factor that may influence the outcomes of DCD kidney transplantation.MethodsWe compared the transplant outcomes in patients receiving DCD kidneys preserved by machine perfusion (MP) or by static cold storage (CS) preservation by conducting a meta-analysis. The MEDLINE, EMBASE and Cochrane Library databases were searched. All studies reporting outcomes for MP versus CS preserved DCD kidneys were further considered for inclusion in this meta-analysis. Odds ratios and 95% confidence intervals (CI) were calculated to compare the pooled data between groups that were transplanted with kidneys that were preserved by MP or CS.ResultsFour prospective, randomized, controlled trials, involving 175 MP and 176 CS preserved DCD kidney transplant recipients, were included. MP preserved DCD kidney transplant recipients had a decreased incidence of delayed graft function (DGF) with an odd ration of 0.56 (95% CI?=?0.36-0.86, P?=?0.008) compared to CS. However, no significant differences were seen between the two technologies in incidence of primary non-function, one year graft survival, or one year patient survival.ConclusionsMP preservation of DCD kidneys is superior to CS in terms of reducing DGF rate post-transplant. However, primary non-function, one year graft survival, and one year patient survival were not affected by the use of MP or CS for preservation.

| S-EPMC3594243 | biostudies-literature

Machine Retrograde Perfusion of Deceased Donor Kidneys: A Prospective Study.

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Oxygenated machine perfusion at room temperature as an alternative for static cold storage in porcine donor hearts.

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Mechanisms and treatment of cold-storage-induced microvascular obstructions in normothermic machine perfusion of human kidney

Project description:Human kidneys which were accepted for transplantation and subsequently not used were subjected to ex vivo normothermic machine perfusion. During perfusion it was found the tubular epithelia synthesized fibrinogen which led to red blood cell aggregation and pathologic plugging of renal microvasculature. Sequential ex vivo delivery of plasminogen and tissue plasminogen activator (tPA) during normothermic machine perfusion effectively lyses these fibrinogen-mediated plugs.

2022-10-01 | GSE139017 | GEO

Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation.

Project description:Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms.We investigated the benefits of pre-reperfusion treatment with recombinant human C1INH (rhC1INH), inhibitor of both complement and contact activation, in a pig model of kidney autotransplantation, subjecting the organ to 60 min warm ischemia prior to 24 h static preservation to maximize damage.Serum creatinine measurement showed that treated animals recovered glomerular function quicker than the Vehicle group. However, no difference was observed in tubular function recovery, and elevated level of urinary NGal (Neutrophil gelatinase-associated lipocalin) and plasma AST (Aspartate Aminotransferase) were detected, indicating that treatment did not influence IRI-mediated tubular cell necrosis. Regarding chronic graft outcome, rhC1INH significantly prevented fibrosis development and improved function. Immunohistochemistry and western blot showed decreased invasion by macrophages and T lymphocytes, and reduction of epithelial to mesenchymal transition. We determined the effect of treatment on complement activation with immunofluorescence analyses at 30 min post reperfusion, showing an inhibition of C4d deposition and MBL staining in treated animals.In this model, the inhibition of complement activation by rhC1INH at reperfusion, while not completely counteracting IRI, limited immune system activation, significantly improving graft outcome on the short and long term.

| S-EPMC5035455 | biostudies-literature

Kidney Donor Profile Index Does Not Accurately Predict the Graft Survival of Pediatric Deceased Donor Kidneys.

Project description:The new deceased donor kidney allocation algorithm uses a Kidney Donor Profile Index (KDPI) based on donor characteristics to predict graft survival and divides kidneys into 4 quality groups (ie, KDPI-A, -B, -C, and -D). Pediatric kidneys constitute 10% to 12% of deceased donor kidneys. We hypothesized that KDPI would not accurately predict pediatric donor graft survival and superior predictive models could be created.Scientific Registry of Transplant Recipients data for years 2000 to 2010 for transplants from child (<10 years) and adolescent (10-17 years inclusive) donors into first-time adult recipients were analyzed with graft failure as the principle outcome. Two novel indices, Child Donor Index (CDI) and Adolescent Donor Index (ADI), were developed using stepwise variable deletion to identify significant model covariates in a Cox Regression. Pediatric donor kidneys were then classified into the 4 quality groups based on both KDPI and CDI/ADI scores. The performance of the KDPI, CDI, and ADI models were compared with respect to the 4 quality groups defined by the new allocation system.The KDPI did not effectively discriminate between quality groups (P > 0.05 for all but 1 comparison) in Kaplan-Meier survival analyses. The CDI and ADI included novel variables (eg, body mass index percentiles) and successfully discriminated between quality groups (P < 0.05 by log rank test). The Net Reclassification Index showed improvement when switching from KDPI to CDI and ADI, with values of 0.09 (P < 0.001) and 0.073 (P < 0.001), respectively.The KDPI does not accurately predict pediatric kidney graft survival. Alternative indices can improve allocation efficiency.

| S-EPMC4940335 | biostudies-literature

The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles.

Project description:A key attribute for nanoparticles (NPs) that are used in medicine is the ability to avoid rapid uptake by phagocytic cells in the liver and other tissues. Poly(ethylene glycol) (PEG) coatings has been the gold standard in this regard for several decades. Here, we examined hyperbranched polyglycerols (HPG) as an alternate coating on NPs. In earlier work, HPG was modified with amines and subsequently conjugated to poly(lactic acid) (PLA), but that approach compromised the ability of HPG to resist non-specific adsorption of biomolecules. Instead, we synthesized a copolymer of PLA-HPG by a one-step esterification. NPs were produced from a single emulsion using PLA-HPG: fluorescent dye or the anti-tumor agent camptothecin (CPT) were encapsulated at high efficiency in the NPs. PLA-HPG NPs were quantitatively compared to PLA-PEG NPs, produced using approaches that have been extensively optimized for drug delivery in humans. Despite being similar in size, drug release profile and in vitro cytotoxicity, the PLA-HPG NPs showed significantly longer blood circulation and significantly less liver accumulation than PLA-PEG. CPT-loaded PLA-HPG NPs showed higher stability in suspension and better therapeutic effectiveness against tumors in vivo than CPT-loaded PLA-PEG NPs. Our results suggest that HPG is superior to PEG as a surface coating for NPs in drug delivery.

| S-EPMC4062180 | biostudies-literature

Transcriptomic analysis of Kidney Machine normothermic perfusion and comparision to cold storage

Project description:Transcriptomic analysis of Kidney Machine normothermic perfusion and comparision to cold storage

| PRJNA497370 | ENA

Proteomic Analysis of Perfusate from Machine Cold Perfusion of Transplant Kidneys: Insights Into Protection from Injury.

Project description:BACKGROUND Machine cold perfusion is beneficial to the preservation of kidneys for transplantation. At the end of preservation, the perfusion solution contains many proteins. Using a proteomics approach, we searched for useful biomarkers and potential therapeutic targets in the perfusate. Our program is unique in that all transplant kidneys (even living donor kidneys, LKD) are placed on machine cold perfusion prior to transplantation. MATERIAL AND METHODS Perfusates from donation after neurological and circulatory determination of death (DNDD and DCDD respectively) and LKD were collected (n=41) and analyzed for LDH, neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-2 (MMP-2) as markers of injury. Perfusate from each kidney was subjected to 2-dimensional gel electrophoresis, then analyzed using software to identify those spots which are significantly different between the 3 groups. Mass spectrometry was used to identify the proteins and their identity was confirmed with Western blot. RESULTS The highest levels of MMP-2, LDH, and NGAL were seen for the DCDD kidneys, followed by the DNDD kidneys and then LDK. Peroxiredoxin-2, NGAL, and alpha-1-antitrypsin were identified as significantly different between the different types of donor kidneys, and their role and possible therapeutic strategies are discussed. Collagen fragments, albumin, and immunoglobulin were also identified as possible byproducts of the injury and may be useful is assessing the degree of injury. CONCLUSIONS Comparison of the perfusates from the different types of kidneys has allowed us to identify proteins that will be useful in future research into reducing injury in transplant kidneys.

| S-EPMC6248313 | biostudies-literature

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