Molecular predictors for anaemia after kidney transplantation.
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.


CONCLUSIONS
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.
Wilflingseder
Julia
J
Department of Nephrology, KH Elisabethinen, Linz, Austria.
Kainz
Alexander
A
Perco
Paul
P
Korbély
Reka
R
Mayer
Bernd
B
Oberbauer
Rainer
R
D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D001317:Austria; D016022:Case-Control Studies; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D005964:Glucosyltransferases; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006397:Hematinics / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism
D055233:Cornified Envelope Proline-Rich Proteins; D006397:Hematinics; D012333:RNA, Messenger; C524773:SPRR2C protein, human; C514116:B3GLCT protein, human; D005700:Galactosyltransferases; D005964:Glucosyltransferases; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase