Transcriptomics,Multiomics

Dataset Information

5

Molecular Phenotypes of Acute Kidney Injury in Kidney Transplants


ABSTRACT: 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. AKI biopsies sample names and CEL files are from GSE21374. All consenting renal transplant patients undergoing biopsies for cause as standard of care between 09/2004 and 10/2007 at the university of Alberta or between 11/2006 and 02/2007 at the University of Illinois were included in the analysis. In addition to the cores required for standard histopathology, we collected one core for gene expression studies. the relationship between gene expression in the biopsy and subsequent graft loss was analyzed.

OTHER RELATED OMICS DATASETS IN: PRJNA144381

SUBMITTER: Declan G de Freitas   Konrad S Famulski  Philip F Halloran 

PROVIDER: E-GEOD-30718 | ArrayExpress | 2012-02-21

SECONDARY ACCESSION(S): GSE30718PRJNA144381

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-30718.README.txt Txt
E-GEOD-30718.idf.txt Idf
E-GEOD-30718.processed.1.zip Processed
E-GEOD-30718.raw.1.zip Raw
E-GEOD-30718.raw.2.zip Raw
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Publications

Molecular phenotypes of acute kidney injury in kidney transplants.

Famulski Konrad S KS   de Freitas Declan G DG   Kreepala Chatchai C   Chang Jessica J   Sellares Joana J   Sis Banu B   Einecke Gunilla G   Mengel Michael M   Reeve Jeff J   Halloran Philip F PF  

Journal of the American Society of Nephrology : JASN 20120216 5


Little is known regarding the molecular phenotype of kidneys with AKI because biopsies are performed infrequently. However, all kidney transplants experience acute injury, making early kidney transplants an excellent model of acute injury, provided the absence of rejection, because donor kidneys should not have CKD, post-transplant biopsies occur relatively frequently, and follow-up is excellent typically. Here, we used histopathology and microarrays to compare indication biopsies from 26 transp  ...[more]

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