Aiming to further the investigation of markers in pre-implantation biopsies (PIB) for the prediction of delayed graft function (DGF), we analyzed, in a different cohort of transplants, the expression of five genes selected from a previous large scale gene expression study in PIB performed at our laboratory: ACSL4 (acyl-CoA synthetase long-chain family member 4), CUBN (cubilin), DEFB1 (defensin, beta 1), FABP3 (fatty acid binding protein, and GK (glycerol kinase). Gene expression was measured with real-time TaqMan PCR assays, in 22 PIBs with DGF, and in 21 PIBs without. Three reference genes (POLR2K, HPRT1, GUSB) were used for gene expression normalization. Lower expression levels of DEFB1 (p=0.004), FABP3 (p=0.001), and GK (p=0.016) were observed in PIBs with DGF, whereas no statistically significant differences were observed concerning ACSL4 or CUBN. The association of low expression levels of DEFB1 with DGF could be reflecting the decrease in the number of tubular cells due to ischemia-induced cell death, since this gene encodes an antimicrobial peptide of urogenital tissues constitutively produced by renal tubular cells (Zhao C et al, 1996; Valore EV et al, 1998). The lower levels of FABP3 in the DGF group could be interpreted as a decrease in protection against ischemic damage, considering that fatty acid-binding proteins have been shown to minimize the tissue damage caused by ischemia by reducing the effects of oxidative stress through the binding of fatty acids and products of lipid peroxidation (Kamijo-Ikemori A et al, 2006; Yamamoto T et al, 2007). An explanation for the association of low GK expression with DGF could be that low levels of glycerol kinase compromise the phosphorylation of glycerol, resulting in increased glycerol levels which were shown to induce acute kidney injury in mice (Homsi E et al, 2006; Rahib L et al, 2007). In a multivariate analysis, including also clinical variables, only FABP3 expression remained independently associated with DGF. FABP3 expression lower than -1.32 log2 transformed units of relative expression conferred an odds ratio for DGF of 41.1. In summary, this study revealed FABP3 expression in PIB as a marker for DGF, and disclosed new genes possibly involved in the pathogenesis of DGF.

CITATION INFORMATION: Mourão T, Mine K, Campos E, Medina-Pestana J, Tedesco-Silva H, Gerbase-De Lima M. Predicting Delayed Kidney Graft Function with Gene Expression in Preimplantation Biopsies. Am J Transplant. 2016;16 (suppl 3).

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