Background: Left ventricular hypertrophy (LVH), which is a pervasive complication of end-stage kidney disease (ESKD), persists in some uremic individuals even after kidney transplantation (Ktx), contributing to worsening CV outcomes. Marinobufagenin (MBG), an endogenous steroid cardiotonic hormone endowed with natriuretic and vasoconstrictive properties, is an acknowledged trigger of uremic cardiomyopathy. However, its clinical significance in the setting of Ktx remains undefined. Methods: In a cohort of chronic Ktx recipients (n = 40), we assessed circulating MBG together with a thorough clinical and echocardiographic examination. Forty matched haemodialysis (HD) patients and thirty healthy subjects served as controls for MBG measurements. Patients were then prospectively followed up to 12 months and the occurrence of an established cardio-renal endpoint (death, CV events, renal events, graft rejection) was recorded. Results: Median MBG plasma levels were lower in Ktx as compared with HD patients (p = 0.02), but higher as compared with healthy controls (p = 0.0005). Urinary sodium (β = 0.423; p = 0.01) and eGFR (β = −0.324; p = 0.02) were the sole independent predictors of MBG in this cohort, while a strong correlation with left ventricular mass index (LVMi), found in univariate analyses (R = 0.543; p = 0.0007), gained significance only in multivariate models not including eGFR. Logistic regression analyses indicated MBG as a significant predictor of the combined endpoint (OR 2.38 [1.10–5.12] per each 1 nmoL/L increase; p = 0.01), as well as eGFR, LVMi, serum phosphate and proteinuria. Conclusions: Ktx recipients display altered MBG levels which are influenced by sodium balance, renal impairment and the severity of LVH. Thus, MBG might represent an important missing link between reduced graft function and pathological cardiac remodelling and may hold important prognostic value for improving cardio-renal risk assessment.

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.

Uremic Cardiomyopathy (UCM) is an irreversible cardiovascular complication that is highly pervasive among chronic kidney disease (CKD) patients, particularly in End-Stage Kidney Disease (ESKD) individuals undergoing chronic dialysis. Features of UCM are an abnormal myocardial fibrosis, an asymmetric ventricular hypertrophy with subsequent diastolic dysfunction and a complex and multifactorial pathogenesis where underlying biological mechanisms remain partly undefined. In this paper, we reviewed the key evidence available on the biological and clinical significance of micro-RNAs (miRNAs) in UCM. miRNAs are short, noncoding RNA molecules with regulatory functions that play a pivotal role in myriad basic cellular processes, such as cell growth and differentiation. Deranged miRNAs expression has already been observed in various diseases, and their capacity to modulate cardiac remodeling and fibrosis under either physiological or pathological conditions is well acknowledged. In the context of UCM, robust experimental evidence confirms a close involvement of some miRNAs in the key pathways that are known to trigger or worsen ventricular hypertrophy or fibrosis. Moreover, very preliminary findings may set the stage for therapeutic interventions targeting specific miRNAs for ameliorating heart damage. Finally, scant but promising clinical evidence may suggest a potential future application of circulating miRNAs as diagnostic or prognostic biomarkers for improving risk stratification in UCM as well.

BACKGROUND AND AIMS Chronic haemodialysis (HD) patients are notoriously at high risk for cardiovascular mortality and morbidity. Omentin-1 (OME-1) is an adipocytokine produced by adipose tissue, whose levels are altered in various dysmetabolic conditions, such as obesity and type 2 diabetes mellitus. Beyond this, nowadays there is evidence indicating that this cytokine plays a crucial role in the genesis and progression of systemic atherosclerosis since it may inhibit plaque formation. With this background in mind, we run a pilot investigation to evaluate the possible correlation between circulating OME-1 levels and mean intimal thickness (IMT) in a small, homogeneous cohort of patients treated by HD (‘HD patients’). METHOD From a source cohort of 45 HD patients, we selected 27 individuals suitable to be enrolled. These patients had a dialysis vintage &gt; 6 mo.,  were on a regular 4 h/3 times week HD regimen and had stable clinical conditions. OME-1 levels were measured in their blood by the ELISA together with common laboratory and clinical parameters before starting a mid-week HD session. All the patients then underwent carotid Doppler ultrasound for IMT measurement. A total of 18 healthy subjects were the controls. RESULTS In the whole cohort, mean IMT values were 0.75 ± 0.12 mm. However, 8/27 patients (29.6%) presented a pathological IMT (&gt;1 mm). Circulating OME-1 levels in the whole HD cohort were increased as compared with controls [763 (367–1423) versus 371 (228–868) ng/mL; P = 0.03]. However, HD patients with pathological IMT presented, on average, lower OME-1 levels as compared with others [483.25 (168.7–1743) versus 1155 (286–2324); P = 0.05]. In ROC analyses, OME-1 values ≤ 840 ng/mL held an 83.3 sensitivity and 66.7 specificity (AUC 0.716, 95% confidence interval 0.506–0.946) in identifying HD patients with pathological carotid thickening. CONCLUSION OME-1 may play a direct role in the atherosclerosis process also in HD patients. Further studies on larger and more heterogeneous HD cohorts are needed to confirm the usefulness of OME-1 plasma levels as potential biomarkers for diagnosing subclinical atherosclerosis and for stratifying the risk of atherosclerosis progression in high-CV risk in HD patients.

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 &lt; 0.0001]. Within 48 h from CPB end, 12/45 patients (27%) developed AKI, as defined as an increase in serum creatinine &gt;0.3 mg/dL or an absolute 1.5-fold increase from baseline and/or a reduced urine output (&lt;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 &lt; 0.001]. 8 h SEPP1: 638 (437–1254) versus 1959 (1055–5303) ng/mL; P &lt; 0.001; difference between overall trends: P &lt; 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 &lt; 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.