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Abstract Background and Aims In the post-hoc analyses of the SUSTAIN and ASSURE trials (Kidney Blood Press Res. 2018;43:449-457), Apabetalone, an epigenetic modulator which lowers serum alkaline phosphatase (AlkPhos), stabilized the GFR in patients with cardiovascular disease and a GFR

Background/Objectives: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are significant public health issues, with cardiovascular morbidity and mortality being the leading causes of death in hemodialysis patients. Osteopontin (OPN), a multifunctional glycoprotein, has emerged as a potential biomarker for vascular disease in CKD due to its role in inflammation, tissue remodeling, and calcification. Methods: This cohort study included 1124 hemodialysis patients from the PROGREDIRE study, a registry involving 35 dialysis units in Southern Italy. Serum osteopontin levels were measured using enzyme-linked immunosorbent assay (ELISA). The primary endpoints were all-cause and cardiovascular mortality. Multivariate Cox regression analyses were performed to assess the association between osteopontin levels and mortality, adjusting for traditional risk factors, biomarkers of inflammation, nutritional status, and ESKD-related factors. Results: During a mean follow-up of 2.8 years, 478 patients died, 271 from cardiovascular causes. Independent correlates of osteopontin included alkaline phosphatase and parathyroid hormone. Elevated osteopontin levels were significantly associated with increased all-cause mortality (HR 1.19, 95% CI 1.09–1.31, p < 0.001) and cardiovascular mortality (HR 1.22, 95% CI 1.08–1.38, p = 0.001) after adjusting for confounders. Conclusions: Elevated osteopontin levels are associated with increased all-cause and cardiovascular mortality in hemodialysis patients. These findings implicate osteopontin in the high risk for death and cardiovascular disease in the hemodialysis population. Intervention studies are needed to definitively test this hypothesis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Acute kidney injury (AKI) remains a significant complication following major cardiac surgery. Marinobufagenin (MBG), a cardiotonic steroid involved in sodium balance and blood pressure regulation, has been linked to organ damage after ischemia–reperfusion events. This pilot, prospective study investigates the utility of circulating MBG to improve AKI risk assessment in cardiac surgery patients as a stand-alone biomarker and after inclusion in a validated risk model (STS-AKI score). Materials and Methods: We included 45 patients undergoing elective cardiac surgery. The MBG levels were measured preoperatively and at 4, 8, and 12 h post-surgery. The AKI was defined according to the KDIGO guidelines. Statistical analyses assessed the diagnostic and prognostic utility of MBG and its integration with the STS-AKI score. Results: An AKI occurred in 26.7% of the patients. The STS-AKI score performed well in this cohort (AUC: 0.736). The MBG levels displayed a decreasing trend in the whole population after surgery (p = 0.02). However, in the AKI patients, MBG increased at 4 and 8 h before decreasing at 12 h post-surgery. The MBG changes from the baseline to 8 h and from 8 to 12 h post-surgery showed a remarkable diagnostic accuracy for an AKI (AUCs: 0.917 and 0.843, respectively). Integrating these MBG changes with the STS-AKI score significantly improved the model performance, including discrimination, calibration, and risk reclassification. Conclusions: The MBG measurement, particularly any dynamic changes post-surgery, enhances AKI risk stratification in cardiac surgery patients. Integrating MBG with the STS-AKI score offers more accurate risk predictions, potentially leading to better patient management and outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease (CKD) is a complex health condition that interacts significantly with socioeconomic determinants, particularly income status and education. This study developed a simple indicator of socioeconomic status (SES), which is composed of income status and education in CKD patients, and evaluated its impact on health outcomes in this population. Methods: This study was conducted on 561 CKD patients, stages 2–5. The composite SES score was developed by combining the regression coefficients of income and education as predictors of the study endpoint in a multivariable Cox model, normalizing these coefficients to derive weights, and then using these weights to calculate an individual percentage score based on each person's income and education. The composed SES indicator was internally validated through bootstrap analysis. Over a median follow-up time of 36 months, we tracked all-cause death and non-fatal cardiovascular events. Results: Both lack of income (p = 0.020) and low educational level (p = 0.034) were independently related to the combined endpoint. Based on these covariates' regression coefficients, a composite socioeconomic score considering income and educational level was generated. In a Cox regression model, a 10% increase in this composite risk score entailed a 25% increase in the hazard ratio (HR) of the combined endpoint [HR (10% increase): 1.25], and the internally validated 95% CI ranged from 1.14 to 1.41 (p < 0.001). Conclusions: This study underscores the significant impact of a simple, bootstrap-validated composite SES indicator on CKD patients' health outcomes. These findings highlight the importance of considering education and socioeconomic factors in managing and treating CKD patients and inform future research and policy considerations for this population. [ABSTRACT FROM AUTHOR]

Background: Biomarkers development for prognostication or prediction of perioperative myocardial disease is critical for the evolution of treatment options in patients undergoing cardiac surgery. The aim of our prospective monocentric study was to investigate the role of selenoprotein 1 (SEEP 1) as a potential biomarker for assessing the risk of myocardial injury after cardiac surgery. 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); (3) Results: circulating SEPP-1 levels measured 4 h after surgery were strongly correlated with CK-MB levels measured at 48 h (R = 0.598, p < 0.0001) and at 72 h (R = 0.308, p = 0.05). Close correlations were also found between 4 h SEPP-1 and Hs-c troponin values measured at 24 h (R = 0.532, p < 0.0001), 48 h (R = 0.348, p = 0.01) and 72 h (R = 0.377, p = 0.02), as well as with cardiopulmonary bypass (CPB) (R = 0.389, p = 0.008) and cross-clamp time (R = 0.374, p = 0.001); (4) Conclusions: Early SEPP1 measurement after CPB may hold great potential for identifying cardiac surgery patients at risk of developing perioperative myocardial injury. [ABSTRACT FROM AUTHOR]

Background Biomarkers of chronic kidney disease–mineral and bone disorder (CKD-MBD) have been implicated in CKD progression in follow-up studies focusing on single measurements of individual biomarkers made at baseline only. The simultaneous relationship between the time trend of these biomarkers over the course of CKD and renal outcomes has never been tested. Methods We applied the joint model (JM) to investigate the longitudinal relationship between repeated measurements of CKD-MBD biomarkers and a combined renal endpoint (estimated glomerular filtration rate reduction >30%, dialysis or transplantation) in 729 stage 2–5 CKD patients over a 36-month follow-up. Results In the survival submodel of the JM, the longitudinal series of parathyroid hormone (PTH) values was directly and independently related to the risk of renal events [hazard ratio (HR) (1 ln increase in parathyroid hormone (PTH) 2.0 (range 1.5–2.8), P  < .001)] and this was also true for repeated measurements of serum phosphate [HR (1 mg/dl) 1.3924 (range 1.1459–1.6918), P  = .001], serum calcium [HR (1 mg/dl) 0.7487 (range 0.5843–0.9593), P  = .022], baseline fibroblast growth factor 23 [HR (1 pg/ml) 1.001 (range 1.00–1.002), P  = .045] and 1,25-dihydroxyvitamin D [HR (1 pg/ml) 0.9796 (range 0.9652–0.9942), P  = .006]. Conclusion Repeated measurements of serum PTH, calcium and phosphate as well as baseline FGF23 and 1,25-dihydroxyvitamin D are independently related with the progression to kidney failure in a cohort of stage 2–5 CKD patients. This longitudinal study generates the hypothesis that interventions at multiple levels on MBD biomarkers can mitigate renal function loss in this population. [ABSTRACT FROM AUTHOR]

Background Adherence to low salt diets and control of hypertension remain unmet clinical needs in chronic kidney disease (CKD) patients. Methods We performed a 6-month multicentre randomized trial in non-compliant patients with CKD followed in nephrology clinics testing the effect of self-measurement of urinary chloride (69 patients) as compared with standard care (69 patients) on two primary outcome measures, adherence to a low sodium (Na) diet (<100 mmol/day) as measured by 24-h urine Na (UNa) excretion and 24-h ambulatory blood pressure (ABPM) monitoring. Results In the whole sample (N  = 138), baseline UNa and 24-h ABPM were143 ± 64 mmol/24 h and 131 ± 18/72 ± 10 mmHg, respectively, and did not differ between the two study arms. Patients in the active arm of the trial used >80% of the chloride strips provided to them at the baseline visit and at follow-up visits. At the third month, UNa was 35 mmol/24 h (95% CI 10.8–58.8 mmol/24 h; P = 0.005) lower in the active arm than the control arm, whereas at 6 months the between-arms difference in UNa decreased and was no longer significant [23 mmol/24 h (95% CI −5.6–50.7); P = 0.11]. The 24-h ABPM changes as well as daytime and night-time BP changes at 3 and 6 months were similar in the two study arms (Month 3, P = 0.69–0.99; Month 6, P = 0.73–0.91). Office BP, the use of antihypertensive drugs, estimated Glomerular Filtration Rate (eGFR) and proteinuria remained unchanged across the trial. Conclusions The application of self-measurement of urinary chloride to guide adherence to a low salt diet had a modest effect on 24-h UNa and no significant effect on 24-h ABPM. [ABSTRACT FROM AUTHOR]

Background Thrombomodulin (TM) is a proteoglycan highly represented in the endothelial glycocalix that regulates the haemostasis and the endothelial response to inflammation. High soluble TM levels underlie a lower risk for coronary heart disease in population studies. Activation of vitamin D receptor (VDR) upregulates TM, but the effect of this intervention on soluble TM has never been tested in chronic kidney disease (CKD) patients. Methods We performed a post hoc analysis of a 12 weeks double blind, randomized, placebo-controlled trial testing the effect of VDR activation by paricalcitol (PCT) on endothelium-dependent flow - mediated vasodilatation (FMD) in the forearm (ClinicalTrials.gov identifier: NCT01680198). Circulating TM was measured in the whole CKD population [88 patients: PCT n  = 44; placebo n  = 44] that took part into this trial. Results Soluble TM at baseline was inversely related to the glomerular filtration rate (r  = −0.65, P < 0.001) and to FMD (Spearman's ρ = −0.29, P = 0.01). Alongside the expected effects on bone mineral biomarkers, PCT produced a consistent rise (P = 0.005) in TM levels, from a median value of 8446.0 pg/mL [interquartile range (IQR): 6227.8–10 910.8 pg/mL] to 9127.5 pg/mL (6393.0–11 287.3 pg/mL) while placebo had no effect (between-groups difference P = 0.008). TM levels re-approached baseline values 2 weeks after stopping PCT. TM changes across the trial paralleled simultaneous changes in FMD. Conclusions VDR activation by PCT raises TM levels and FMD and such effects are rapidly reversible after stopping the treatment. The TM rise induced by PCT is a possible mechanism whereby improvement in endothelial function by VDR activation may favourably impact upon vascular health in CKD patients. [ABSTRACT FROM AUTHOR]