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Diagnosing Rejection in Renal Transplants: A Comparison of Molecular- and Histopathology-Based Approaches
Article first published online: 10 JUN 2009
DOI: 10.1111/j.1600-6143.2009.02694.x
© 2009 The Authors Journal compilation © 2009 The American Society of Transplantation and the American Society of Transplant Surgeons
Additional Information
How to Cite
Reeve, J., Einecke, G., Mengel, M., Sis, B., Kayser, N., Kaplan, B. and Halloran, P. F. (2009), Diagnosing Rejection in Renal Transplants: A Comparison of Molecular- and Histopathology-Based Approaches. American Journal of Transplantation, 9: 1802–1810. doi: 10.1111/j.1600-6143.2009.02694.x
Publication History
- Issue published online: 16 JUL 2009
- Article first published online: 10 JUN 2009
- Received 23 December 2008, revised 09 March 2009 and accepted for publication 02 April 2009
Keywords:
- Allograft rejection;
- Banff schema;
- microarrays;
- prediction
Predicting rejection using microarray data from kidney transplant biopsies shows high concordance with histopathology diagnoses, but comparison of the two methods offers insights that may further improve diagnostic accuracy.
The transcriptome has considerable potential for improving biopsy diagnoses. However, to realize this potential the relationship between the molecular phenotype of disease and histopathology must be established. We assessed 186 consecutive clinically indicated kidney transplant biopsies using microarrays, and built a classifier to distinguish rejection from nonrejection using predictive analysis of microarrays (PAM). Most genes selected by PAM were interferon-γ—inducible or cytotoxic T-cell associated, for example, CXCL9, CXCL11, GBP1 and INDO. We then compared the PAM diagnoses to those from histopathology, which are based on the Banff diagnostic criteria. Disagreement occurred in approximately 20% of diagnoses, principally because of idiosyncratic limitations in the histopathology scoring system. The problematic diagnosis of ‘borderline rejection’ was resolved by PAM into two distinct classes, rejection and nonrejection. The diagnostic discrepancies between Banff and PAM in these cases were largely due to the Banff system's requirement for a tubulitis threshold in defining rejection. By examining the discrepancies between gene expression and histopathology, we provide external validation of the main features of the histopathology diagnostic criteria (the Banff consensus system), recommend improvements and outline a pathway for introducing molecular measurements.