scholarly journals The mRNA landscape profiling reveals potential biomarkers associated with acute kidney injury AKI after kidney transplantation

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10441
Author(s):  
Hui Bi ◽  
Min Zhang ◽  
Jialin Wang ◽  
Gang Long
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Graft Function ◽  
Kidney Injury ◽  
Diagnostic Value ◽  
Hub Genes ◽  
Key Genes ◽  
Potential Biomarkers

Background This study aims to identify potential biomarkers associated with acute kidney injury (AKI) post kidney transplantation. Material and Methods Two mRNA expression profiles from Gene Expression Omnibus repertory were downloaded, including 20 delayed graft function (DGF) and 68 immediate graft function (IGF) samples. Differentially expressed genes (DEGs) were identified between DGF and IGF group. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of DEGs were performed. Then, a protein-protein interaction analysis was performed to extract hub genes. The key genes were searched by literature retrieval and cross-validated based on the training dataset. An external dataset was used to validate the expression levels of key genes. Receiver operating characteristic curve analyses were performed to evaluate diagnostic performance of key genes for AKI. Results A total of 330 DEGs were identified between DGF and IGF samples, including 179 up-regulated and 151 down-regulated genes. Of these, OLIG3, EBF3 and ETV1 were transcription factor genes. Moreover, LEP, EIF4A3, WDR3, MC4R, PPP2CB, DDX21 and GPT served as hub genes in PPI network. EBF3 was significantly up-regulated in validation GSE139061 dataset, which was consistently with our initial gene differential expression analysis. Finally, we found that LEP had a great diagnostic value for AKI (AUC = 0.740). Conclusion EBF3 may be associated with the development of AKI following kidney transplantation. Furthermore, LEP had a good diagnostic value for AKI. These findings provide deeper insights into the diagnosis and management of AKI post renal transplantation.

scholarly journals Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jolanta Malyszko ◽  
Ewelina Lukaszyk ◽  
Irena Glowinska ◽  
Magdalena Durlik
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Graft Function ◽  
Kidney Injury ◽  
Delayed Graft Function

scholarly journals Impact of deceased donor with acute kidney injury on subsequent kidney transplant outcomes–an ANZDATA registry analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249000
Author(s):  
Juan Pei ◽  
Yeoungjee Cho ◽  
Yong Pey See ◽  
Elaine M. Pascoe ◽  
Andrea K. Viecelli ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Failure ◽  
Cox Regression ◽  
Graft Function ◽  
Kidney Injury ◽  
Deceased Donor ◽  
Hazard Ratio

Background The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature. Material and methods This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection. Results The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99–1.26), death-censored graft failure (HR 1.09, 95% CI 0.92–1.28), death (HR 1.15, 95% CI 0.98–1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91–1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92–2.68). Conclusion Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

scholarly journals Identification of fibroblast activation-related genes in two acute kidney injury models

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10926
Author(s):  
Weiming Deng ◽  
Xiangling Wei ◽  
Zhanwen Dong ◽  
Jinhua Zhang ◽  
Zhengyu Huang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Hub Genes ◽  
Fibroblast Activation ◽  
Qrt Pcr ◽  
Early Activation

BackgroundIschemia-reperfusion injury and drug-induced nephrotoxicity are the two most common reasons for acute kidney injury (AKI). However, little attention has been paid to early activation of fibroblasts in the progression of AKI to chronic kidney disease (CKD). The present study aimed to identify related genes and pathways on fibroblast activation in two mouse models of AKI: ischemia-reperfusion injury (IRI) model and folic acid (FA)-induced injury model.MethodsThe microarray expression profiles ofGSE62732andGSE121190were downloaded from the GEO database, and the differentially expressed genes (DEGs) was analyzed using the Limma package of R software. Principal component analysis (PCA) was also performed using R. The functional information of gene products was annotated by Gene Ontology (GO) and DAVID online database, and the pathway analysis was carried out by using the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Protein-protein interactions (PPI) network was constructed by STRING and Cytoscape. Furthermore, in the Hypoxia/Reoxygenation (H/R) model, the morphological changes of cells were observed under microscope and the expression of the hub genes in NRK-49F cells were validated by qRT-PCR assays.ResultsA total of 457 DEGs were identified. Among these, 215 DEGs were upregulated and 242 DEGs were downregulated in the acute injured samples compared with uninjured samples. The GO enrichment analysis indicated that these DEGs were mainly involved in transport, the oxidation-reduction process, the metabolic process, metal ion binding, hydrolase activity, and oxidoreductase activity. The KEGG analysis revealed that these DEGs were significantly enriched in the PI3K-Akt signaling pathway, protein digestion and absorption pathway, and focal adhesion pathway. The hub genes including Hnf4α, Pck1 and Timp1 were validated by the qRT-PCR assay in NRK-49F cells in the H/R model.ConclusionsHnf4α, Pck1 and Timp-1 may play a pivotal role in the early activation of fibroblasts, providing novel therapeutic strategies for early prediction and treatment of renal fibrosis.

scholarly journals Histopathology and Long-Term Outcome of Kidneys Transplanted From Donors With Severe Acute Kidney Injury

2018 ◽  
Vol 29 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Luca Cima ◽  
Francesco Nacchia ◽  
Claudio Ghimenton ◽  
Giovanni Valotto ◽  
Luigino Boschiero ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Acute Tubular Necrosis ◽  
Statistical Significance ◽  
Graft Function ◽  
Kidney Injury ◽  
Long Term Outcome ◽  
Tubular Necrosis ◽  
Level 3

Background: Acute kidney injury is a treatable entity although difficult to recognize without diagnostic biopsy. We investigated the potential association between clinically defined deceased donors and acute kidney injury with preimplantation histological findings and recipient outcomes. Methods: Kidney biopsies from donors were classified using the Acute Kidney Injury Network criteria and assessed for percentage glomerulosclerosis, tubular atrophy, interstitial fibrosis, and vascular narrowing with the Remuzzi score and for acute tubular necrosis. Differences in incidence rates of delayed graft function (DGF) and cumulative rejection episodes were compared between recipients transplanted with normal and 3 levels of acute kidney injury using the analysis of variance with Bonferroni correction ( P = .0012). Results: Sixteen out of 335 donors showed a severe acute kidney injury level 3 with a median serum creatinine of 458 µmol/L. Fourteen (88%) had 0-3 Remuzzi score and were used for single kidney transplantation and 2 (12%) were used for dual kidney transplantation (score: 4-6). Recipients who received a kidney from a donor with level 3 acute kidney injury had a higher percentage of DGF (47%) without statistical significance ( P = .008). The rate of cumulative rejection (45%) at 2 years was not significantly increased ( P = .09). Conclusions: Recipients receiving level 3 acute kidney injury kidneys, selected with Remuzzi histopathological score and acute tubular necrosis assessment, had a greater incidence of DGF but a similar long-term cumulative rejection compared to no injury and level 1 and level 2 acute kidney injury donors. The application of the histopathological examination allowed expansion of the kidney donor pool.

scholarly journals Impact of acute kidney injury on graft outcomes of deceased donor kidney transplantation: A nationwide registry-based matched cohort study in Korea

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260076
Author(s):  
Jane Ha ◽  
Cheol Woong Jung ◽  
Sunkyu Choi ◽  
Myung-Gyu Kim ◽  
Jun Gyo Gwon ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Confidence Interval ◽  
Graft Failure ◽  
Patient Survival ◽  
Graft Function ◽  
Kidney Injury ◽  
Asian Population ◽  
Rejection Rate ◽  
Cox Proportional Hazards

Background Favorable long-term and short-term graft survival and patient survival after kidney transplantation (KT) from deceased donors with acute kidney injury (AKI) have been reported. However, few studies have evaluated effects of donor AKI status on graft outcomes after KT in Asian population. Thus, the purpose of this study was to evaluate graft function after KTs from donors with AKI compared to matched KTs from donors without AKI using a multicenter cohort in Korea. Methods We analyzed a total of 1,466 KTs collected in Korean Organ Transplant Registry between April 2014 and December 2017. KTs from AKI donors (defined as donors with serum creatinine level ≥ 2 mg/dL) and non-AKI donors (275 cases for each group) were enrolled using a 1:1 propensity score matching. Graft outcomes including graft and patient survival, delayed graft function (DGF), rejection rate, and serially measured estimated glomerular filtration rate (eGFR) were evaluated. Results After propensity matching, KTs from AKI donors showed higher rate of DGF (44.7% vs. 24.0%, p < 0.001). However, the rejection rate was not significantly different between the two groups (KTs from AKI donors vs. KTs from non-AKI donors). eGFRs measured after 6 months, 1 year, 2 years and 3 years were not significantly different by donor AKI status. With median follow-up duration of 3.52 years, cox proportional hazards models revealed hazard ratio of 0.973 (95% confidence interval [CI], 0.584 to 1.621), 1.004 (95% CI, 0.491 to 2.054) and 0.808 (95% confidence interval [CI], 0.426 to 1.532) for overall graft failure, death-censored graft failure and patient mortality, respectively, in KTs from AKI donors compared to KTs from non-AKI donors as a reference. Conclusions KTs from AKI donors showed comparable outcomes to KTs from non-AKI donors, despite a higher incidence of DGF. Results of this study supports the validity of using kidneys from deceased AKI donors in Asian population.

Predicting Hub Genes of Glioblastomas Based on Support Vector Machine Combined with CFS algorithms

2020 ◽  
Vol 15 ◽  
Author(s):  
Chun Qiu ◽  
Sai Li ◽  
Shenghui Yang ◽  
Lin Wang ◽  
Aihui Zeng ◽  
...  
Keyword(s):  
Support Vector Machine ◽  
Expression Profiles ◽  
Independent Set ◽  
Classification Model ◽  
Support Vector ◽  
Feature Subset ◽  
Hub Genes ◽  
Effective Prevention ◽  
Key Genes ◽  
Control Samples

Aim: To search the genes related to the mechanisms of the occurrence of glioma and to try to build a prediction model for glioblastomas. Background: The morbidity and mortality of glioblastomas are very high, which seriously endangers human health. At present, the goals of many investigations on gliomas are mainly to understand the cause and mechanism of these tumors at the molecular level and to explore clinical diagnosis and treatment methods. However, there is no effective early diagnosis method for this disease, and there are no effective prevention, diagnosis or treatment measures. Methods: First, the gene expression profiles derived from GEO were downloaded. Then, differentially expressed genes (DEGs) in the disease samples and the control samples were identified. After that, GO and KEGG enrichment analyses of DEGs were performed by DAVID. Furthermore, the correlation-based feature subset (CFS) method was applied to the selection of key DEGs. In addition, the classification model between the glioblastoma samples and the controls was built by an Support Vector Machine (SVM) based on selected key genes. Results and Discussion: Thirty-six DEGs, including 17 upregulated and 19 downregulated genes, were selected as the feature genes to build the classification model between the glioma samples and the control samples by the CFS method. The accuracy of the classification model by using a 10-fold cross-validation test and independent set test was 76.25% and 70.3%, respectively. In addition, PPP2R2B and CYBB can also be found in the top 5 hub genes screened by the protein– protein interaction (PPI) network. Conclusions: This study indicated that the CFS method is a useful tool to identify key genes in glioblastomas. In addition, we also predicted that genes such as PPP2R2B and CYBB might be potential biomarkers for the diagnosis of glioblastomas.

scholarly journals Safety and effectiveness of kidney transplantation using a donation after brain death donor with acute kidney injury: a retrospective cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyeong Deok Kim ◽  
Kyo Won Lee ◽  
Sang Jin Kim ◽  
Okjoo Lee ◽  
Manuel Lim ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Brain Death ◽  
Graft Survival ◽  
Low Dose ◽  
Kidney Injury ◽  
Induction Agent ◽  
Donor Pool ◽  
Donation After Brain Death

AbstractThe use of kidneys from donation after brain death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.

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