Relation between renal dysfunction requiring renal replacement therapy and promoter polymorphism of the erythropoietin gene in cardiac surgery

Several genetic polymorphisms have been identified to play a role in the occurrence and progression of renal dysfunction after cardiac surgery with cardiopulmonary bypass (CPB). Recently, it was demonstrated that the T allele of SNP rs1617640 in the promoter of the erythropoetin (EPO) gene is significantly associated with proliferative diabetic retinopathy (PDR) and end-stage renal disease (ESRD) due to increased EPO expression. This disease risk-associated gene and its potential pathway mediating severe microvascular complications in T-allele carriers could also play a role on renal dysfunction in patients who underwent cardiac surgery with CPB. We hypothesized that the patients' ability to produce increased EPO concentrations will affect morbidity and mortality after CPB. We conducted a prospective single center study between April 2006 and May 2007. In 481 patients who underwent cardiac surgery with CPB we prospectively examined the SNP rs1617640 in the promoter of the EPO gene by DNA sequencing. The patients were grouped according to their genotype (GG, GT, and TT). The genotype distribution of SNP rs1617640 in the promoter of the EPO gene was 36% (TT), 49% (TG), and 15% (GG). There was no difference in age, body mass index, gender, CPB time, or length of stay in intensive care unit. The hospitalization was irrespective of the patients' genotypes. The baseline creatinine in the TT group was 0.2 points higher than in the other groups; however this was without statistical significance in the multivariate analysis. No significant difference was shown in Euroscore, the Simplified Acute Physiology Score II, the Acute Physiology and Chronic Health Evaluation Score II, Acute Renal Failure Score, or the Risk, Injury, Failure, Loss of Kidney Function Score. The mortality was equal across the genotypes. However, an association between the TT genotype and acute renal replacement therapy (P=0.03), intra-aortic balloon pump usage (P=0.02), and serum creatine phosphokinase-MB increase (P=0.03) were observed after cardiac surgery. Our analysis suggests that the risk allele (T) of rs1617640 plays a role in the development of renal dysfunction after cardiac surgery with CPB. Patients with the TT risk allele required more frequent acute renal replacement therapy. Since our result is close to the border of significance, this hypothesis should be investigated in larger prospective studies with long-term follow-up to emphasize this polymorphism as a potential risk factor.