SELENIUM-BINDING PROTEIN 1 (SEPP1) AS AN EARLY SENSITIVE BIOMARKER OF ACUTE KIDNEY INJURY IN PATIENTS UNDERGOING CARDIOPULMONARY BYPASS

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) often occurs in patients undergoing major cardiac surgery with cardiopulmonary bypass (CPB). Despite renal ischemia remains the key trigger, sustained oxidative stress is now acknowledged as a significant contributor. Selenium-binding protein 1 (SEPP1) is an intracellular protein whose blood levels increase in response to systemic cardiovascular and oxidative stress, as well as in the course of chronic kidney injury. METHOD In this pilot prospective study, we measured circulating SEPP1 levels in a cohort of 45 patients undergoing cardiac surgery with CPB in order to test its possible role in predicting the following occurrence of AKI. Serum samples of SEPP1 were collected before CPB (baseline) and at 4, 8 and 12 h after the end of the procedure and measured with a commercially available ELISA kit. RESULTS In the whole cohort, there was a significant statistical trend in SEPP1 levels from baseline to 12 h after CPB [39 (10–45) versus 3263 (1886–5042) ng/mL; P < 0.0001]. Within 48 h from CPB end, 12/45 patients (27%) developed AKI, as defined as an increase in serum creatinine >0.3 mg/dL or an absolute 1.5-fold increase from baseline and/or a reduced urine output (<0.5 mL/kg/h). Circulating SEPP1 displayed an earlier and more prominent increase in AKI patients as compared with others [4 h SEPP1: 52 (39–233) versus 546 (260–1000) ng/mL; P < 0.001]. 8 h SEPP1: 638 (437–1254) versus 1959 (1055–5303) ng/mL; P < 0.001; difference between overall trends: P < 0.001 (Fig. 1). At ROC analyses, either 4 or 8 h circulating SEPP1 had a remarkable diagnostic capacity in identifying AKI patients (AUCs 0.854 and 0.790, both P < 0.001). The crude OR of AKI in patients with 4 and 8 h SEPP1 above the best ROC-derived cut-off values (178 and 1840 ng/mL, respectively) was 22 (95%CI 2.5–192.9) and 14.5 (95% CI 2.9–71.2), respectively. At multivariate analysis, such a risk was independent from potential confounders, including CPB duration, clamping time and age. CONCLUSION Increased SEPP1 levels in patients undergoing CPB may reflect a sustained response to systemic oxidative stress. Such a response becomes more prominent when renal damage is also occurring. Studies on larger and more heterogeneous cohorts are needed to confirm whether SEPP1 may be a candidate as an early and specific biomarker of AKI in this high-risk setting.