Selenoprotein P-1 (SEPP1) as an Early Biomarker of Acute Kidney Injury in Patients Undergoing Cardiopulmonary Bypass

Abstract

Background: Acute Kidney Injury (AKI) is a frequent, dangerous complication in patients undergoing cardiopulmonary bypass (CPB) with oxidative stress playing a crucial role. In this pilot study we evaluated the possible role of the selenoprotein-p1 (SEPP1), a circulating, anti-oxidant selenium transporter, as a predictive biomarker of AKI in this population setting. Methods: Circulating SEPP1 was measured in the blood of 45 patients before surgery and at 4 h, 8 h and 12 h after CPB by Enzyme-Linked Immunosorbent Assay (ELISA). Results: SEPP1 increased from 69 to 3263 [IQR 1886.2-5042.7] ng/mL (p for trend <0.0001). AKI occurred in 26.7% of patients. In these individuals, an earlier and more prominent increase in SEPP1 was observed at 4 h and 8 h, as compared with those not experiencing AKI (difference between trends p < 0.0001). Logistic regression analyses evidenced 4 h and 8 h SEPP1 as significantly associated with AKI (OR 1.035; 95% CI 1.002-1.068; p = 0.03 and 1.011; 95% CI 1.002-1.021; p = 0.02, respectively). ROC analyses displayed a remarkable discriminatory capacity of early SEPP1 measurements in identifying AKI (AUCs ranging from 0.682 to 0.854; p from 0.04 to <0.0001). In addition, 12 h-SEPP1 showed diagnostic capacity to identify patients reaching a secondary composite endpoint including major adverse kidney events (MAKEs). Conclusions: Findings from this pilot, exploratory study suggest that early SEPP1 measurement after CPB may hold great potential for improving renal risk stratification in cardiac surgery patients. Further studies in wider and more heterogeneous cohorts are needed to generalize these findings and to evaluate a possible applicability in daily practice.

Selenoprotein-P1 (SEPP1) Expression in Human Proximal Tubule Cells after Ischemia-Reperfusion Injury: An In Vitro Model

“…In a recent paper, we established SEPP1 as an early and promising biomarker for acute kidney injury in patients undergoing major cardio-surgery operation. SEPP1 increased particularly between the 4th and 8th hours after CPB and with a strict relation with ischemia duration [ 9 ]. In the same paper, we were unable to demonstrate if this plasmatic protein, mainly of hepatic origin, accumulates due to decreased filtration by damaged glomeruli or if renal tubules augment the expression of SEPP1 as a defeat mechanism [ 9 ].…”

“…SEPP1 increased particularly between the 4th and 8th hours after CPB and with a strict relation with ischemia duration [ 9 ]. In the same paper, we were unable to demonstrate if this plasmatic protein, mainly of hepatic origin, accumulates due to decreased filtration by damaged glomeruli or if renal tubules augment the expression of SEPP1 as a defeat mechanism [ 9 ]. However, in our present experiments, we demonstrated that tubular cells injured by hypoxia indeed upregulate SEPP1 expression.…”

“…While serum creatinine remains the cornerstone for assessing renal function, its limitations in detecting the early stages of AKI and its delayed responsiveness underscore the necessity to find alternative biomarkers. Recently, in our pilot study on patients undergoing elective major cardiac surgery with cardiopulmonary bypass (CPB), selenoprotein-p1 (SEPP1) has emerged as a promising candidate plasmatic biomarker for an early AKI risk stratification [ 9 ]. SEPP1 acts as a selenium transporter, supplying tissues and organs with this trace mineral.…”

Selenoprotein P-1 (SEPP1) as an Early Biomarker of Myocardial Injury in Patients Undergoing Cardiopulmonary Bypass

“…According to a pilot research study we recently published, early assessment of selenium P-1 (SEPP1) following cardiopulmonary bypass grafting (CPB) may be very beneficial for enhancing renal risk stratification in patients undergoing heart surgery [4]. Although SEPP 1's existence was initially documented over thirty years ago, the last 10 years have seen many advancements in our understanding of its functions.…”

Holistic Vision of Cardiovascular Complications in Chronic Kidney Disease

“…For these reasons, investigation of early biomarkers of acute kidney damage are of increasing interest. In a recent pilot study, Bolignano et al [11] showed that selenoprotein-p1 (SEPP1), a circulating, anti-oxidant selenium transporter, could be a useful predictive biomarker of AKI in patients undergoing CPB. Specifically, circulating SEPP1 release occurs early (at 4 and 8 hours) in patients with AKI; conversely, no difference was noted 12 hours after surgery compared with the control group.…”