Project description:Transcriptional profiling of mouse kidney tissue comparing control untreated mice with mice treated with cisplatin. The latter makes kidney failure. Goal was to identify the alterations of N6-methyladenosine (m6A) RNA profiles in cisplatin-induced acute kidney injury (AKI) in mice.
Project description:The goal of this observational study is to compare anesthetic modalities (intravenous propofol anesthesia with sevoflurane gas anesthesia) in patients who underwent colorectal cancer resection surgery regarding the outcome of acute kidney injury.
The main questions it aims to answer are:
* is there a difference in acute kidney injury incidence in the two anesthetic modalities?
* is there a difference in plasma creatinine between the two anesthetic modalities?
* are there any patient characteristics or intraoperative factors that effect the incidence of acute kidney injury in either anesthetic modality?
The study will analyze data from the CAN clinical trial database. (Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia, NCT01975064)
Project description:Kidney tissues from a cisplatin-induced acute kidney injury mouse model of global Apobec1 knockout mice compared with wild type mice. 6 months old male mice examined. We used microarrays to identify genes that are differentially expressed during acute kidney injury in the absence of apobec1 compared with wild type mice.
Project description:After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this “failed-repair proximal tubule cell” or FR-PTC, state can be detected in other models of kidney injury, increasing in the aging rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair.
Project description:18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChipM-BM-. miRNA 3.0 Array. Comparison between control group (protocol biopsies) and indication biopsies with histological lesions of acute tubular necrosis without rejection (ATN).
Project description:18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChip® Human Gene 2.0 ST Array. comparison between control group (protocol biopsies) and indication biopsies with histological lesions of acute tubular necrosis without rejection (ATN)
Project description:Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers.
Project description:A quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI), an abrupt loss of kidney function that doubles the risk of death at one-year. There is a critical need to identify early markers for AKI in ADHF, however, no protein candidates have been validated as diagnostic or prognostic biomarkers in this setting. We aimed to identify novel candidate protein biomarkers by quantifying changes in protein expression in the kidney that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using Sequential Window Acquisition of All Theoretical Mass Spectrometry (SWATH-MS) in kidney cortex from healthy control sheep (n=5), sheep with established rapid pacing-induced ADHF (n=8) and sheep after ~4 weeks recovery from ADHF (n=7). Of 790 proteins quantified, we identified 17 candidate kidney injury markers, one potential marker of kidney recovery and two markers of long-term renal impairment that were differentially expressed between groups (1.2-2.6 fold-change, p<0.05). Differentially expressed proteins were enriched in pro-inflammatory signaling pathways: Glycoprotein VI (activated during ADHF development, adjusted p<0.01) and acute phase response (repressed during recovery from ADHF, p<0.01). This research identified 20 candidate protein markers of kidney injury, including 6 promising candidates supported by existing evidence and 14 novel candidates never implicated in AKI. Early awareness of AKI in ADHF through the use of biomarkers has the potential to reduce mortality and improve outcomes for these at-risk patients.