Selenoprotein P is associated with selective glomerular hypofiltration syndrome and future hospitalization for kidney failure among patients with acute heart failure

Abstract Background Selenium (Se), a trace element, has emerged as a potential biomarker of poor prognosis in both in heart failure (HF) and kidney failure (KF). Se-deficiency has previously been associated with increased mortality and specifically, cardiovascular mortality. Serum-Se is constituted by several components but is mainly transported by Selenoprotein P (SP), commonly used as a surrogate marker for Se-status. "Selective glomerular hypofiltration syndrome" (SGHS) has been shown to function as an early indicator of kidney function impairment. Impaired kidney function, in this study defined as a) presence of SGHS upon baseline and/or b) future hospitalization due to KF, among patients with HF is a dreaded complication associated with increased mortality. Purpose To explore if SP is associated with SGHS at baseline and/or future hospitalization due to KF in patients with acute HF. Methods Creatinine (Crea) and Cystatin C (CysC) were analyzed in 570 patients hospitalized for acute HF, of which initial consecutive 311 subjects also had SP analyzed by an immunoassay analysis. SGHS was derived from the CAPA Lund-Malmö Equations for Glomerular Filtration Rate (GFR) and defined as a CysC-based estimated GFR (eGFR) 60% of the Crea based eGFR. KF hospitalizations were extracted using ICD10 codes N17-N19. Multivariate regression models were deployed to explore a) SP´s association with prevalence of SGHS at baseline and b) SP´s association with hospitalization for KF, adjusting for age, sex, systolic blood pressure, BMI and eGFR. Results The study population had a mean age of 74 (±12) years and 67% were male. In total, 83 patients (14.5%) had SGHS at baseline. During follow-up, 46 patients were hospitalized for KF. Basic characteristics are presented in Table 1. SP was associated with the prevalence of SGHS (odds ratio (OR) 0.50; 95%CI 0.33-0.74; p0.001) and also with a higher risk of hospitalization due to chronic or acute KF (N17-N19) (hazard ratio (HR) 0.55; 95%CI 0.36-0.83; p=0.005), and due to acute KF (N17-N17.9) (HR 0.36; 95%CI 0.20-0.65; p0.001). Using a cut-off aligned with Se-deficiency (SP3.4mg/L, corresponding to approximately S-Se70 μg/L), the association with hospitalization due to acute KF remained significant (HR 4.06; 95%CI 1.11-14.80; p=0.034), while the association with hospitalization due to acute or chronic or acute KF was attenuated (HR 1.96; 95%CI 0.85-4.49; p=0.114). Conclusions Here, we demonstrate an association between low levels of Selenoprotein P and the presence of selective glomerular hypofiltration syndrome. Furthermore, we show that lower levels of selenoprotein P are associated with an increased risk of future hospitalization due to kidney failure. These findings underscore the emerging body of evidence identifying selenium deficiency as a potential contributor the pathophysiology of both heart failure and kidney failure. Further research is needed to better understand the mechanisms underlying these associations.