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      Oxidative Stress in ESRD Patients on Dialysis and the Risk of Cardiovascular Diseases

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          Abstract

          Chronic kidney disease is highly prevalent worldwide. The decline of renal function is associated with inadequate removal of a variety of uremic toxins that exert detrimental effects on cells functioning, thus affecting the cardiovascular system. The occurrence of cardiovascular aberrations in CKD is related to the impact of traditional risk factors and non-traditional CKD-associated risk factors, including anemia; inflammation; oxidative stress; the presence of some uremic toxins; and factors related to the type, frequency of dialysis and the composition of dialysis fluid. Cardiovascular diseases are the most frequent cause for the deaths of patients with all stages of renal failure. The kidney is one of the vital sources of antioxidant enzymes, therefore, the impairment of this organ is associated with decreased levels of these enzymes as well as increased levels of pro-oxidants. Uremic toxins have been shown to play a vital role in the onset of oxidative stress. Hemodialysis itself also enhances oxidative stress. Elevated oxidative stress has been demonstrated to be strictly related to kidney and cardiac damage as it aggravates kidney dysfunction and induces cardiac hypertrophy. Antioxidant therapies may prove to be beneficial since they can decrease oxidative stress, reduce uremic cardiovascular toxicity and improve survival.

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          Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.

          End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern. An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency. Copyright 2004 Massachusetts Medical Society
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            Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis

            Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD is usually asymptomatic until later stages and accurate prevalence data are lacking. Thus we sought to determine the prevalence of CKD globally, by stage, geographical location, gender and age. A systematic review and meta-analysis of observational studies estimating CKD prevalence in general populations was conducted through literature searches in 8 databases. We assessed pooled data using a random effects model. Of 5,842 potential articles, 100 studies of diverse quality were included, comprising 6,908,440 patients. Global mean(95%CI) CKD prevalence of 5 stages 13·4%(11·7–15·1%), and stages 3–5 was 10·6%(9·2–12·2%). Weighting by study quality did not affect prevalence estimates. CKD prevalence by stage was Stage-1 (eGFR>90+ACR>30): 3·5% (2·8–4·2%); Stage-2 (eGFR 60–89+ACR>30): 3·9% (2·7–5·3%); Stage-3 (eGFR 30–59): 7·6% (6·4–8·9%); Stage-4 = (eGFR 29–15): 0·4% (0·3–0·5%); and Stage-5 (eGFR<15): 0·1% (0·1–0·1%). CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 to 13% with the majority stage 3. Future research should evaluate intervention strategies deliverable at scale to delay the progression of CKD and improve CVD outcomes.
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              Gout-associated uric acid crystals activate the NALP3 inflammasome.

              Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a 'danger signal' released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1beta and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1beta receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                03 November 2020
                November 2020
                : 9
                : 11
                : 1079
                Affiliations
                [1 ]Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-419 Łódź, Poland; jacek.rysz@ 123456umed.lodz.pl (J.R.); bfranczyk-skora@ 123456wp.pl (B.F.)
                [2 ]Department of Urology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland; janlaw@ 123456wp.pl
                Author notes
                [* ]Correspondence: aniagluba@ 123456yahoo.pl ; Tel.: +48-42-639-3750
                Author information
                https://orcid.org/0000-0003-3322-5655
                Article
                antioxidants-09-01079
                10.3390/antiox9111079
                7693989
                33153174
                0e5e6c9f-bf8f-4214-9e22-512bcc9be1d9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 September 2020
                : 27 October 2020
                Categories
                Review

                end-stage renal disease,oxidative stress,cardiovascular disease,antioxidant therapy

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