Amplification of oxidative stress is present since the early stages of chronic kidney disease (CKD), holding a key position in the pathogenesis of renal failure. Induction of renal pro-oxidant ...enzymes with excess generation of reactive oxygen species (ROS) and accumulation of dityrosine-containing protein products produced during oxidative stress (advanced oxidation protein products-AOPPs) have been directly linked to podocyte damage, proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) as well as tubulointerstitial fibrosis. Vascular oxidative stress is considered to play a critical role in CKD progression, and ROS are potential mediators of the impaired myogenic responses of afferent renal arterioles in CKD and impaired renal autoregulation. Both oxidative stress and inflammation are CKD hallmarks. Oxidative stress promotes inflammation via formation of proinflammatory oxidized lipids or AOPPs, whereas activation of nuclear factor κB transcription factor in the pro-oxidant milieu promotes the expression of proinflammatory cytokines and recruitment of proinflammatory cells. Accumulating evidence implicates oxidative stress in various clinical models of CKD, including diabetic nephropathy, IgA nephropathy, polycystic kidney disease as well as the cardiorenal syndrome. The scope of this review is to tackle the issue of oxidative stress in CKD in a holistic manner so as to provide a future framework for potential interventions.
Increased serum levels of uric acid have been associated with the onset and development of chronic kidney disease (CKD), cardiovascular disease, and mortality, through several molecular pathogenetic ...mechanisms, such as inflammation and oxidative stress. Oxidative stress is present even in the early stages of CKD, progresses parallelly with the deterioration of kidney function, and is even more exacerbated in end-stage renal disease patients undergoing maintenance hemodialysis. Although acting in the plasma as an antioxidant, once uric acid enters the intracellular environment; it behaves as a powerful pro-oxidant. Exogenous intake of antioxidants has been repeatedly shown to prevent inflammation, atherosclerosis and oxidative stress in CKD patients. Moreover, certain antioxidants have been proposed to exert uric acid-lowering properties. This review aims to present the available data regarding the effects of antioxidant supplements on both oxidative stress and uric acid serum levels, in a population particularly susceptible to oxidative damage such as CKD patients.
Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo ...vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed.
The vascular endothelium is a dynamic, functionally complex organ, modulating multiple biological processes, including vascular tone and permeability, inflammatory responses, thrombosis, and ...angiogenesis. Endothelial dysfunction is a threat to the integrity of the vascular system, and it is pivotal in the pathogenesis of atherosclerosis and cardiovascular disease. Reduced nitric oxide (NO) bioavailability is a hallmark of chronic kidney disease (CKD), with this disturbance being almost universal in patients who reach the most advanced phase of CKD, end-stage kidney disease (ESKD). Low NO bioavailability in CKD depends on several mechanisms affecting the expression and the activity of endothelial NO synthase (eNOS). Accumulation of endogenous inhibitors of eNOS, inflammation and oxidative stress, advanced glycosylation products (AGEs), bone mineral balance disorders encompassing hyperphosphatemia, high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23), and low levels of the active form of vitamin D (1,25 vitamin D) and the anti-ageing vasculoprotective factor Klotho all impinge upon NO bioavailability and are critical to endothelial dysfunction in CKD. Wide-ranging multivariate interventions are needed to counter endothelial dysfunction in CKD, an alteration triggering arterial disease and cardiovascular complications in this high-risk population.
Oxidative stress (OS) is the result of prooxidant molecules overwhelming the antioxidant defense mechanisms. Hemodialysis (HD) constitutes a state of elevated inflammation and OS, due to loss of ...antioxidants during dialysis and activation of white blood cells triggering production of reactive oxygen species. Dialysis vintage, dialysis methods, and type and condition of vascular access, biocompatibility of dialyzer membrane and dialysate, iron administration, and anemia all can play a role in aggravating OS, which in turn has been associated with increased morbidity and mortality. Oral or intravenous administration of antioxidants may detoxify the oxidative molecules and at least in part repair OS‐mediated tissue damage. Lifestyle interventions and optimization of a highly biocompatible HD procedure might ameliorate OS development in dialysis.
COVID-19 and the kidney: time to take a closer look Liakopoulos, Vassilios; Roumeliotis, Stefanos; Papachristou, Stella ...
International urology and nephrology,
05/2022, Letnik:
54, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Although coronavirus disease (COVID-19) is primarily a respiratory disease, the kidney may be among the target organs of infection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ...Independently of baseline kidney function, acute kidney injury (AKI) is a common complication of COVID-19, associated with increased mortality and morbidity. Most frequently, COVID-19 causes acute tubular necrosis; however, in some cases, collapsing focal segmental glomerulosclerosis and direct viral tropism of the kidneys have also been documented. AKI secondary to COVID-19 has a multi-factorial origin. Even mild impairment of renal function is an independent risk factor for COVID-19 infection, hospitalisation and mortality. Dialysis patients also carry an increased risk of other severe COVID-related complications, including arrhythmias, shock, acute respiratory distress syndrome and acute heart failure. In such patients, COVID-19 may even present with atypical clinical symptoms, including gastrointestinal disorders and deterioration of mental status. More research is needed on the exact effects of SARS-CoV-2 on the kidneys. Finally, it remains to be proven whether the outcome of patients with kidney disease may be improved with anticipated vaccination programmes.
Author Affiliation: (1) Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 1, St. ...Kyriakidi Street, 54636, Thessaloniki, Greece (2) Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110, Larissa, Greece (a) steroum.roum@gmail.com Article History: Registration Date: 12/12/2020 Accepted Date: 12/08/2020 Online Date: 02/03/2021 Byline:
We aimed to investigate the possible association of the inactive, dephosphorylated, uncarboxylated matrix Gla protein (dp-ucMGP) with oxidized low-density lipoprotein (ox-LDL) and ...all-cause/cardiovascular (CV) mortality and renal function in diabetic chronic kidney disease (CKD). Ox-LDL and dp-ucMGP were determined in 66 diabetic CKD patients. All patients were prospectively followed for seven years, or until the occurrence of death, or a composite renal outcome of 30% estimated glomerular filtration rate (eGFR) reduction or progression to end-stage renal disease (ESRD) requiring dialysis occurred. Secondary outcomes were the occurrence of CV events. Kaplan-Meier curves showed that patients with plasma dp-ucMGP levels above the median (≥656 pM) had a significantly higher risk for all study endpoints. After adjustment for several well-known cofounders, multivariate Cox analysis showed that high plasma dp-ucMGP levels were associated with all-cause mortality (Hazard ratio-HR = 2.63, 95% Confidence Interval-CI = 1.17-5.94,
= 0.02), CV mortality (HR = 2.82, 95% CI = 1.07-7.49,
= 0.037) and progression of CKD (HR = 4.02, 95% CI = 1.20-13.46,
= 0.024). Circulating dp-ucMGP is associated with mortality and decreased renal function in diabetic CKD.
Diabetic Kidney Disease (DKD) remains the leading cause of Chronic and End Stage Kidney Disease (ESKD) worldwide, with an increasing epidemiological burden. However, still, the disease awareness ...remains low, early diagnosis is difficult, and therapeutic management is ineffective. These might be attributed to the fact that DKD is a highly heterogeneous disease, with disparities and variability in clinical presentation and progression patterns. Besides environmental risk factors, genetic studies have emerged as a novel and promising tool in the field of DKD. Three decades ago, family studies first reported that inherited genetic factors might confer significant risk to DKD development and progression. During the past decade, genome-wide association studies (GWASs) screening the whole genome in large and multi-ethnic population-based cohorts identified genetic risk variants associated with traits defining DKD in both type 1 and 2 diabetes. Herein, we aim to summarize the existing data regarding the progress in the field of genomics in DKD, present how the revolution of GWAS expanded our understanding of pathophysiologic disease mechanisms and finally, suggest potential future directions.
In Chronic Kidney Disease, vascular calcification (VC) is highly prevalent even at early stages and is gradually enhanced, along with disease progression to End-Stage Renal Disease (ESRD). The ...calcification pattern in uremia includes all types of mineralization and contributes to the heavy cardiovascular (CV) burden that is common in these patients. Ectopic mineralization is the result of the imbalance between inhibitors and promoters of vascular calcification, with the latter overwhelming the former. The most powerful, natural inhibitor of calcification is Matrix Gla Protein (MGP), a small vitamin K dependent protein, secreted by chondrocytes and vascular smooth muscle cells. In uremia, MGP was reported as the only molecule able to reverse VC by "sweeping" calcium and hydroxyapatite crystals away from the arterial wall. To become biologically active, this protein needs to undergo carboxylation and phosphorylation, reactions highly dependent on vitamin K status. The inactive form of MGP reflects the deficiency of vitamin K and has been associated with CV events and mortality in ESRD patients. During the past decade, vitamin K status has emerged as a novel risk factor for vascular calcification and CV disease in various populations, including dialysis patients. This review presents evidence regarding the association between vitamin K and CV disease in ESRD patients, which are prone to atherosclerosis and atheromatosis.
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