NDT Advance Access originally published online on April 27, 2009
Nephrology Dialysis Transplantation 2009 24(8):2567-2575; doi:10.1093/ndt/gfp183
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Transcriptome changes in renal allograft protocol biopsies at 3 months precede the onset of interstitial fibrosis/tubular atrophy (IF/TA) at 6 months
1 Novartis Pharma AG, Basel, Switzerland 2 Spheromics, Kontiolahti, Finland 3 Department of Nephrology, Medizinische Hochschule Hannover, Hannover, Germany 4 Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, Canada
Correspondence and offprint requests to: Andreas Scherer; E-mail: Andreas.Scherer{at}Spheromics.com
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Abstract |
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Background. Interstitial fibrosis and tubular atrophy (IF/TA) in renal transplants are the major morphological correlates of progressive graft deterioration. Early diagnosis of IF/TA is a pre-requisite for a timely therapeutic intervention in patients at risk. To evaluate events occurring before the overt onset of IF/TA, gene expression profiling of 3-month protocol biopsies from patients with IF/TA was performed in a patient group (n = 8) who developed mild IF/TA [chronic allograft nephropathy (CAN) grade I, by the Banff scoring system] in the subsequent 6-month protocol biopsy (‘progressors’), and in 12 patients without IF/TA at 6 months (‘non-progressors’).
Methods. RNA was extracted, labelled and hybridized to human specific genome wide DNA microarrays. Normalized data were subjected to gene-centric and pathway-centric statistical methods.
Results. Compared to the non-progressors, the 3-month biopsies of the progressor group showed overexpression of several genes that are important in the T- and B-cell activation and immune response. Genes involved in pro-fibrotic processes were identified in the biopsies of the progressors that preceded the observed IF/TA at 6 months. Furthermore, several genes with transporter and metabolic functions were underrepresented in the progressors in the 3-month biopsies.
Conclusion. Gene expression profiling of early protocol biopsies identified changes in the transcriptome of grafts, which may be important for the development of IF/TA. Such early detection of transcriptome changes can facilitate the identification of patients at risk shifting the intervention time point well before the histological diagnosis of irreversible IF/TA.
Keywords: gene expression profiling; IF/TA; protocol biopsy
Received for publication: 25. 6.08
Accepted in revised form: 30. 3.09