Molecular correlates of renal function in kidney transplant biopsies

Sakarn Bunnag, Gunilla Einecke, Jeff Reeve, Gian S. Jhangri, Thomas F. Mueller, Banu Sis, Luis G. Hidalgo, Michael Mengel, Daniel Kayser, Bruce Kaplan, Philip F. Halloran

    Research output: Contribution to journalArticlepeer-review

    60 Scopus citations

    Abstract

    The molecular changes in the parenchyma that reflect disturbances in the function of kidney transplants are unknown. We studied the relationships among histopathology, gene expression, and renal function in 146 human kidney transplant biopsies performed for clinical indications. Impaired function (estimated GFR) correlated with tubular atrophy and fibrosis but not with inflammation or rejection. Functional deterioration before biopsy correlated with inflammation and tubulitis and was greater in cases of rejection. Microarray analysis revealed a correlation between impaired renal function and altered expression of sets of transcripts consistent with tissue injury but not with those consistent with cytotoxic T cell infiltration or IFN-γ effects. Multivariate analysis of clinical variables, histologic lesions, and transcript sets confirmed that expression of injury-related transcript sets independently correlated with renal function. Analysis of individual genes confirmed that the transcripts with the greatest positive or negative correlations with renal function were those suggestive of response to injury and parenchymal dedifferentiation not inflammation. We defined new sets of genes based on individual transcripts that correlated with renal function, and these highly correlated with the previously developed injury sets and with atrophy and fibrosis. Thus, in biopsies performed for clinical reasons, functional disturbances are reflected in transcriptome changes representing tissue injury and dedifferentiation but not the inflammatory burden.

    Original languageEnglish (US)
    Pages (from-to)1149-1160
    Number of pages12
    JournalJournal of the American Society of Nephrology
    Volume20
    Issue number5
    DOIs
    StatePublished - May 2009

    ASJC Scopus subject areas

    • Nephrology

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