Low-density array PCR analysis of reperfusion biopsies: An adjunct to histological analysis

Paolo Cravedi, Umberto Maggiore, Roslyn B. Mannon

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background. Histologic evaluation of baseline kidney biopsies is an inconsistent tool to predict graft outcomes, which might be assisted by gene expression analysis.Methods. We evaluated 49 consecutive kidney graft biopsies obtained post-reperfusion in 18 deceased donors (DD) and 31 living donors (LD) at our center. Biopsies were evaluated and scored using Banff criteria. Low-density real-time polymerase chain reaction arrays were used to measure intragraft expression of 95 genes associated with programmed cell death, fibrosis, innate and adaptive immunity and oxidative stress signaling. A pool of 25 normal kidney biopsies was used as control. We applied a stepwise forward selection procedure to build a multiple regression model predicting estimated glomerular filtration rate (eGFR) at 1 year after transplant using baseline clinical characteristics and gene expression levels.Results. DD grafts displayed a pattern of gene expression remarkably different from LD, including an increased expression of complement protein C3, and chemokines, CXCL1 and CXCL2, consistent with the proinflammatory setting of ischaemia-reperfusion injury. There was no association between any of the reperfusion biopsy histological features and either renal function at 1 year post-transplant or risk of acute rejection. Conversely, older donor age (R2 = 0.17, P < 0.001) and higher integrin β2 gene expression levels (incremental R2 versus Donor Age-only model = 0.23, P < 0.001) jointly predicted lower eGFR at 1 year after transplant (multiple regression R2 = 0.40). Patients with higher ITGβ2 expression levels in baseline biopsies showed lower eGFR, higher levels of proteinuria and more transplant glomerulopathy on the 1-year per-protocol biopsies.Conclusion. ITGβ2 gene expression in reperfusion biopsies may represent a prognostic marker for kidney transplant recipients, potentially helpful in shaping patients' treatment. Further studies are needed to confirm our findings.

Original languageEnglish (US)
Pages (from-to)4077-4086
Number of pages10
JournalNephrology Dialysis Transplantation
Volume25
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • gene expression
  • integrin β2
  • kidney transplant
  • predictor
  • reperfusion biopsy

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Fingerprint Dive into the research topics of 'Low-density array PCR analysis of reperfusion biopsies: An adjunct to histological analysis'. Together they form a unique fingerprint.

  • Cite this