NDT Advance Access originally published online on December 18, 2008
Nephrology Dialysis Transplantation 2009 24(3):1015-1023; doi:10.1093/ndt/gfn683
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Molecular predictors for anaemia after kidney transplantation
1 Department of Nephrology, KH Elisabethinen, Linz 2 Department of Nephrology, Medical University of Vienna, Vienna 3 Emergentec Biodevelopment GmbH, Vienna 4 Austrian Dialysis and Transplant Registry, Wels, Austria
Correspondence and offprint requests to: Rainer Oberbauer, Department of Nephrology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Tel: +43-732-7676-4305; Fax: +43-732-7676-4306; E-mail: rainer.oberbauer{at}meduniwien.ac.at
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Abstract |
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Background. Anaemia of chronic kidney disease is a well-studied comorbidity, but the molecular predictors of post-transplant anaemia remain elusive.
Methods. In this case-control study, 25 subjects with post-transplant anaemia, defined as erythropoiesis-stimulating agent (ESA) requirement within the first post-transplant year, were matched to 25 control recipients with comparable demographics but no anaemia using the Austrian Dialysis and Transplant Registry. Genome-wide gene expression analyses of deceased donor kidney biopsies obtained immediately before engraftment were performed using custom cDNA microarrays. Significant molecular features were included together with clinical variables in a multivariable logistic regression analysis and further analysed with respect to their molecular functions, biological processes and cellular locations using gene ontology terms and protein–protein interactions.
Results. Immunity response molecules were over-represented in the up-regulated gene list suggesting the involvement of the inflammation cascade as a predictor of ESA requirement after engraftment. From the initial list of the 34 differentially expressed genes, we identified the best three genes predicting ESA requirement in the first year by a stepwise gene selection algorithm. SPRR2C (OR = 0.24, 95% CI 0.07–0.85, P = 0.027) and GSTT1 (OR = 2.40, 95% CI 1.21–4.77, P = 0.013) remained significant after adjusting for donor age, eGFR, BCAR and CRP.
Conclusion. In summary, we identified three biomarkers (SPRR2C, B3GALTL and GSTT1) of post-transplant anaemia in donor kidney biopsies that correctly predicted ESA requirement within the first year after transplantation in 93% of the cases.
Keywords: biomarker; erythropoetin; gene expression; inflammation; renal transplantation
Received for publication: 22. 7.08
Accepted in revised form: 17.11.08