Molecular predictors for anaemia after kidney transplantation

Anaemia of chronic kidney disease is a well-studied comorbidity, but the molecular predictors of post-transplant anaemia remain elusive.

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.

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.

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.