Donor-Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes in Kidney Transplantation.

Introduction: Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear.

Methods: We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months.

Advancements in risk stratification and management strategies in primary cardiovascular prevention.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for advancements in risk assessment and management strategies. Although significant progress has been made recently, identifying and managing apparently healthy individuals at a higher risk of developing atherosclerosis and those with subclinical atherosclerosis still poses significant challenges. Traditional risk assessment tools have limitations in accurately predicting future events and fail to encompass the complexity of the atherosclerosis trajectory.

Albumin Redox Modifications Promote Cell Calcification Reflecting the Impact of Oxidative Status on Aortic Valve Disease and Atherosclerosis.

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels.

Targeting the TWEAK-Fn14 pathway prevents dysfunction in cardiac calcium handling after acute kidney injury.

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality.

Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin.

Calcific aortic stenosis (CAS) and type 2 diabetes mellitus (T2DM) are related and often concomitant pathologies, accompanied by common comorbidities such as hypertension or dyslipidemia. Oxidative stress is one of the mechanisms that trigger CAS, and it can drive the vascular complications in T2DM. Metformin can inhibit oxidative stress, yet its effects have not been studied in the context of CAS.

Hypertension mediated kidney and cardiovascular damage and risk stratification: Redefining concepts.

Hypertension mediated organ damage (HMOD) refers to structural or functional changes in arteries or target organs that can be present in long-standing hypertension, but it can be also found in naïve never treated patients. Traditionally, cardiovascular risk is stratified with charts or calculators that tend to underestimate the real cardiovascular risk. The diagnosis of HMOD automatically reclassifies patients to the highest level of cardiovascular risk.

Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling.

Background: Acute renal failure (ARF) following renal ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown.

Methods: We examined intracellular Ca dynamics in adult ventricular cardiomyocytes isolated from C57BL/6 mice 7 or 15 days following unilateral renal I/R.

Results: After 7 days of I/R, the cell contraction was significantly lower in cardiomyocytes compared to sham-treated mice.

Interplay between mineral bone disorder and cardiac damage in acute kidney injury: from Ca mishandling and preventive role of Klotho in mice to its potential mortality prediction in human.

Biomarkers of mineral bone disorders (MBD) including phosphorus, fibroblast growth factor (FGF)-23 and Klotho are strongly altered in patients with acute kidney injury (AKI) who have high cardiac outcomes and mortality rates. However, the crosslink between MBD and cardiac damage after an AKI episode still remains unclear. We tested MBD and cardiac biomarkers in an experimental AKI model after 24 or 72 hours of folic acid injection and we analyzed structural cardiac remodeling, intracellular calcium (Ca) dynamics in cardiomyocytes and cardiac rhythm.

The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23.

Background: Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease.

Cardiovascular Risk Stratification Based on Oxidative Stress for Early Detection of Pathology.

Current cardiovascular (CV) risk prediction algorithms are able to quantify the individual risk of CV disease. However, CV risk in young adults is underestimated due to the high dependency of age in biomarker-based algorithms. Because oxidative stress is associated with CV disease, we sought to examine CV risk stratification in young adults based on oxidative stress to approach the discovery of new markers for early detection of pathology.

An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk.

Fibroblast growth factor-23 (FGF)-23 is a phosphaturic hormone involved in mineral bone metabolism that helps control phosphate homeostasis and reduces 1,25-dihydroxyvitamin D synthesis. Recent data have highlighted the relevant direct FGF-23 effects on the myocardium, and high plasma levels of FGF-23 have been associated with adverse cardiovascular outcomes in humans, such as heart failure and arrhythmias. Therefore, FGF-23 has emerged as a novel biomarker of cardiovascular risk in the last decade.

Analysis of Global Oxidative Status Using Multimarker Scores Reveals a Specific Association Between Renal Dysfunction and Diuretic Therapy in Older Adults.

Aging and chronic kidney disease (CKD) are important interrelated cardiovascular risk (CVR) factors linked to oxidative stress, but this relationship has not been well studied in older adults. We assessed the global oxidative status in an older population with normal to severely impaired renal function. We determined the oxidative status of 93 older adults (mean age 85 years) using multimarker scores.

Oxidized Low-Density Lipoprotein Associates with Ventricular Stress in Young Adults and Triggers Intracellular Ca Alterations in Adult Ventricular Cardiomyocytes.

Oxidized low-density lipoprotein (oxLDL) is associated with cardiac damage and causes injury to multiple cell types. We aimed to investigate the role of oxLDL in ventricular stress. We first examined the association between circulating oxLDL and N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of myocardial stress, in young subjects (30-50 years) with or without stable coronary artery disease (SCAD).

Enhanced Klotho availability protects against cardiac dysfunction induced by uraemic cardiomyopathy by regulating Ca handling.

Background And Purpose: Klotho is a membrane-bound or soluble protein, originally identified as an age-suppressing factor and regulator of mineral metabolism. Klotho deficiency is associated with the development of renal disease, but its role in cardiac function in the context of uraemic cardiomyopathy is unknown.

Experimental Approach: We explored the effects of Klotho on cardiac Ca cycling.

Prediction of the early response to spironolactone in resistant hypertension by the combination of matrix metalloproteinase-9 activity and arterial stiffness parameters.

Aims: The aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH).

Methods And Results: Ambulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH).

Novel molecular plasma signatures on cardiovascular disease can stratify patients throughout life.

Several models are available to calculate the risk of developing cardiovascular complications in mid-life. The estimation of lifetime risk in the long-term remains an unmet clinical need. We previously identified new molecular plasma signatures for cardiovascular risk stratification in a young population (30-50-years old).

Variations in Circulating Active MMP-9 Levels During Renal Replacement Therapy.

Renal replacement therapy (RRT) is complicated by a chronic state of inflammation and a high mortality risk. However, different RRT modalities can have a selective impact on markers of inflammation and oxidative stress. We evaluated the levels of active matrix metalloproteinase (MMP)-9 in patients undergoing two types of dialysis (high-flux dialysis (HFD) and on-line hemodiafiltration (OL-HDF)) and in kidney transplantation (KT) recipients.

Early Posttransplant Mobilization of Monocytic Myeloid-derived Suppressor Cell Correlates With Increase in Soluble Immunosuppressive Factors and Predicts Cancer in Kidney Recipients.

Background: Myeloid-derived suppressor cells (MDSCs) increase in patients with cancer and are associated with poor prognosis; however, their role in transplantation is not yet understood. Here we aimed to study the MDSC effects on the evolution of kidney transplant recipients (KTRs).

Methods: A cohort of 229 KTRs was prospectively analyzed.

Oxidative Status before and after Renal Replacement Therapy: Differences between Conventional High Flux Hemodialysis and on-Line Hemodiafiltration.

Hemodialysis patients experience high oxidative stress because of systemic inflammation and depletion of antioxidants. Little is known about the global oxidative status during dialysis or whether it is linked to the type of dialysis. We investigated the oxidative status before (pre-) and after (post-) one dialysis session in patients subjected to high-flux dialysis (HFD) or on-line hemodiafiltration (OL-HDF).

Resistant hypertension: new insights and therapeutic perspectives.

Resistant hypertension (RH) is a concept that currently goes beyond the classical definition of blood pressure ≥140/90 mmHg in subjects receiving three or more drugs of different classes at maximally tolerated doses. Here, we review the clinical relevance of RH and the different types of RH-associated phenotypes, namely refractory hypertension, controlled resistant hypertension, and masked uncontrolled hypertension. We also discuss current drug strategies and future treatments for these high-risk phenotypes.

Lifetime cardiovascular risk is associated with a multimarker score of systemic oxidative status in young adults independently of traditional risk factors.

Cardiovascular risk (CVR) tends to be estimated in the short-term, which underestimates lifetime (LT)-CVR of young subjects. We determined whether LT-CVR is associated with a multimarker score of oxidative status in young adults and whether this association is independent of traditional CVR factors. Seventy-two young adults were stratified into: (1) low or (2) high LT-CVR, and (3) stable coronary artery disease (SCAD).