Gene Expression Profiles of Transplanted Kidneys from Deceased Donors with Severe Acute Kidney Injury
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE61739 | GEO | 2015/05/22
SECONDARY ACCESSION(S): PRJNA262003
REPOSITORIES: GEO
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Project description:One and four month formalin-fixed paraffin embedded biopsies from 48 kidney transplant recipients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). At one month, there were 898 differentially expressed genes in the AKI group (p-value <0.005; FDR <10%), but by 4-months there were no longer any differences. One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 kidney transplant recipients (24 AKI donors, 24 controls; 96 total samples) were profiled using Affymetrix U133PM Plus PM plate arrays on a GeneTitan MC instrument. All samples were selected from the SCD cohort only. AKI donor and controls samples were matched by date of transplantation. Total RNA was extracted from four 20-micron sections using Ambion RecoverAll Total Nucleic Acid Kit and processed for chip hybridization using the new Affymetrix SensationPlus™ FFPE Amplification and 3’ IVT Labeling kit according to the manufacturer’s protocol. Quantile data normalization by RMA and analysis was performed using Partek Genomics Suite for PDR-corrected differential gene expression by ANOVA. Pathway mapping was performed using Ingenuity Pathway Analysis (IPA). This dataset is part of the TransQST collection.
2015-05-22 | E-GEOD-61739 | biostudies-arrayexpress
Project description:BackgroundSingle-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable.MethodsWe conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function.ResultsWe screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months.ConclusionsOur multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.
| S-EPMC7608971 | biostudies-literature
Project description:NRK cells were exposed to serum-free, 10% FBS (control), 10% serum sampled from rats 24 hours after sham surgery (no kidney injury control), or 10% serum sampled from rats 24 hours after I/R AKI surgery (kidney injury serum). After 48 hours of exposure to serum, the NRK cells were harvested and processed for Agilent microarray We previously conducted a Phase I Clinical Trial in which Mesenchymal Stem/Stromal Cells (MSCs) were administered to patients at risk for developing acute kidney injury (AKI), and which suggested that MSC therapy is safe and effective in preventing both postoperative AKI and progression to CKD. It is well understood that AKI creates an internal environment that adversely affects not only the kidneys but also the function of distant organs and tissues. To study the consequences of the AKI environment on MSCs and renal cells, we developed an in vitro assay of exposing MSCs or cultured tubular cells (NRK Cells) to serum from animals that had AKI, or SHAM surgeries. Compared to SHAM sera, exposure of cells to AKI serum caused increased intra-cellular resazurin reduction, and activation of anti-oxidant genes,
2017-03-16 | GSE94678 | GEO
Project description: Not available
| S-EPMC8405039 | biostudies-literature
Project description:Waitlists are often used to ration scarce resources, but the trade-offs in designing these mechanisms depend on agents' preferences. We study equilibrium allocations under alternative designs for the deceased donor kidney waitlist. We model the decision to accept an organ or wait for a preferable one as an optimal stopping problem and estimate preferences using administrative data from the New York City area. Our estimates show that while some kidney types are desirable for all patients, there is substantial match-specific heterogeneity in values. We then develop methods to evaluate alternative mechanisms, comparing their effects on patient welfare to an equivalent change in donor supply. Past reforms to the kidney waitlist primarily resulted in redistribution, with similar welfare and organ discard rates to the benchmark first come first served mechanism. These mechanisms and other commonly studied theoretical benchmarks remain far from optimal. We design a mechanism that increases patient welfare by the equivalent of an 18.2 percent increase in donor supply.
| S-EPMC8294653 | biostudies-literature
Project description:When encountered, the ideal management of lithiasis in deceased donor kidneys is not well-defined. With advances in endourological techniques, minimally invasive treatments are becoming an increasingly viable option. We set out to describe our experience performing ex-vivo ureteroscopy on cadaveric donor kidneys, including one in which the procedure was completed on-pump.A retrospective chart review was undertaken to identify patients who had undergone ex-vivo ureteroscopy prior to cadaveric renal transplant. Four patients were identified, including one in which the procedure was done with the kidney remaining on-pump. The surgical technique and subsequent data were reviewed.Ex-vivo ureteroscopy was successfully completed in all four instances without intraoperative complication. All kidneys were endoscopically stone-free. Creatinine nadirs ranged from 0.8-1.4. All four patients remained stone-free at a mean followup of 13 months.Our series provides further evidence as to the safety and efficacy of ex-vivo ureteroscopy prior to transplantation in cadaveric renal transplants and describes a novel technique in the form of on-pump ex-vivo ureteroscopy.
| S-EPMC5542832 | biostudies-other
Project description:Background and objectivesIL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.Design, setting, participants, & measurementsWe studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies.ResultsMedian (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99).ConclusionsIn DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.
| S-EPMC5012491 | biostudies-literature
Project description:Sepsis is a severe clinical syndrome related to an exaggerated host immune response to infection as well as systematic inflammation and serious tissue damage. Sepsis-associated acute kidney injury (SA-AKI) is one of the most frequent and serious complications of sepsis. This study aimed to identify new mechanisms in SA-AKI through transcriptome profiling (RNA-seq).
2022-08-17 | GSE186822 | GEO
Project description:Background and objectivesBiopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial.Design, setting, participants, & measurementsWe compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (n=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (n=116 kidneys).ResultsFor kidneys on which more than one procurement biopsy was performed (n=116), category agreement was found in only 64% of cases (κ=0.14). For all kidneys (n=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (κ=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (κ=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (κ=0.13) and 80% (κ=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure.ConclusionsWe found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes.
| S-EPMC6302333 | biostudies-literature
Project description:There is a gap between the number of patients waiting for a transplant and the number of kidneys available. Some deceased donor kidneys are currently nonutilized, as medical teams fear that they will experience suboptimal graft survival. However, these organs could provide an acceptable therapeutic option if they were allocated for preemptive kidney transplantation in elderly candidates. This project aims to gather patients' perspectives on the allocation of kidneys with lower longevity for preemptive kidney transplantation in elderly patients. Individual interviews. The Center hospitalier de l'Université de Montréal (CHUM) chronic kidney disease (CKD) clinic. Patients aged between 64 and 75 years with CKD G4-5 ND, followed at the CHUM and who have not initiated dialysis yet. Between March and July 2023, we conducted 14 individual interviews with patients aged between 64 and 75 years who had CKD G4-5 ND and were followed at the CHUM. The interviews were digitally recorded and transcribed. Thematic analysis was conducted. Most participants were in favor of using kidneys with lower longevity to increase their access to transplantation, improve their quality of life, enable accelerated transplantation, and avoid dialysis. Patients also wanted to be engaged in the decision-making process, underlining the importance of informed consent. Although the use of kidneys with lower longevity offers the hope of returning to "normal" life, some patients were concerned about the risk of reduced graft survival and the need for a subsequent kidney transplant. In these cases, patients were interested in using mitigation strategies, such as prioritization for kidney transplantation from standard donors in case of early graft loss associated with receiving kidneys with lower longevity. They also recommended the development of a separate waiting list for patients consenting to preemptive transplantation with kidneys with lower longevity. This study was conducted in only 1 nephrology clinic in the province of Quebec with French-speaking patients. Consequently, the results may not be generalizable to other populations, including ethnic minorities. The use of kidneys with lower longevity for preemptive kidney transplantation appears to be an interesting option for elderly kidney transplant candidates. However, patient information and participation in the decision-making process are essential. Moreover, organ donation organizations and transplant programs should develop a separate waitlist for transplant candidates who have preconsented to receive organ offers of deceased donor kidneys with lower longevity. Not registered.
| S-EPMC11292676 | biostudies-literature