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- Title
Transcriptome changes in renal allograft protocol biopsies at 3 months precede the onset of interstitial fibrosis/tubular atrophy (IF/TA) at 6 months.
- Authors
Scherer, Andreas; Gwinner, Wilfried; Mengel, Michael; Kirsch, Torsten; Raulf, Friedrich; Szustakowski, Joseph D.; Hartmann, Nicole; Staedtler, Frank; Engel, Guenter; Klupp, Jochen; Korn, Alexander; Kehren, Jeanne; Haller, Hermann
- Abstract
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.
- Subjects
MESSENGER RNA; KIDNEY transplantation; HOMOGRAFTS; RENAL biopsy; MEDICAL protocols; CYSTIC fibrosis; KIDNEY diseases; STATISTICAL correlation; PATIENTS
- Publication
Nephrology Dialysis Transplantation, 2009, Vol 24, Issue 8, p2567
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfp183