Part of the book: Special Problems in Hemodialysis Patients
Part of the book: Chronic Kidney Disease
Part of the book: Psoriasis
Part of the book: From Preconception to Postpartum
Anemia is a common complication of chronic kidney disease (CKD) associated with disease progression and increased mortality. This anemia is mainly due to inadequate production of erythropoietin (EPO) by the failing kidneys, resulting from the reduction in renal EPO‐producing cells (REPC) or from dysregulation of the hypoxia‐inducible factor (HIF) system that regulates several genes related to hypoxia, angiogenesis, fibrosis and glucose metabolism, among others. In this chapter, we present a review on the HIF system in CKD‐anemia, the HIF response to erythropoiesis‐stimulating agents (ESA) therapy and its potential involvement in the development of ESA resistance by enhancing kidney fibrosis and inflammation. Due to concerns related to ESA use, new drugs to correct anemia are under study, being the prolyl hydroxylase inhibitors the most promising candidates.
Part of the book: Hypoxia and Human Diseases
Paediatric obesity has significant physic, social and psychological implications. Childhood obesity is usually associated in adulthood with increased risk of type 2 diabetes, metabolic syndrome and cardiovascular diseases. Aggregation of cardiometabolic risk factors is already observed at young ages, with a nonlinear association with enhancement of adiposity. Adiponectin is an adipokine that inhibits inflammation, oxidative stress and metabolic syndrome components, namely dyslipidaemia, high blood pressure and insulin resistance. Obesity has been associated with hypoadiponectinaemia in both adult and paediatric patients, which may contribute to co‐morbidities observed in these patients. Interventional studies that aim to tackle obesity reported controversial results. Although the general positive effect on weight loss, inflammatory and cardiometabolic markers has been studied, the impact of these interventional studies on adiponectin remains unclear. Some studies reported that the improvement in adiponectin might only occur in paediatric obese patients with great weight loss or intensive physical exercise; the magnitude of the changes in body composition appears to be of particular importance. A revision about the knowledge on the relation between adiponectin, inflammation and cardiometabolic risk factors in paediatric patients is performed; the impact of interventional studies on adiponectin levels and markers of cardiometabolic risk is also addressed.
Part of the book: Adiposity
End-stage renal disease (ESRD) patients present high incidence of cardiovascular (CV) events, which are the most common causes of death in these patients. The occurrence of CV events appears as a consequence of the high prevalence of traditional and non-traditional CV risk factors. Online-hemodiafiltration (OL-HDF) was introduced as a better alternative to conventional dialysis, as it was proposed to be more biocompatible, to increase dialysis efficacy, to reduce the inflammatory response to treatment and to improve patient’s quality of life, contributing to reduce CV and all-cause mortality risk in ESRD. However, data in literature, comparing the effect of OL-HDF with conventional dialysis for clinical CV outcome and all-cause mortality, yielded controversy about those benefits of OL-HFD over standard hemodialysis. A review of the traditional CV risk factors (e.g., arterial hypertension, diabetes mellitus, dyslipidemia, obesity, smoking and advanced age), non-traditional risk factors (e.g., anemia, oxidative stress, hyperphosphatemia, endothelial dysfunction, left ventricular hypertrophy, insulin resistance, high levels of lipoprotein(a) and inflammation) and potential renocardiovascular biomarkers, in the setting of ESRD, is presented. The impact of conventional hemodialysis and OL-HDF on CV risk factors and on the outcome of ESRD patients is also addressed.
Part of the book: Aspects in Dialysis
Inflammation is a common feature in end stage renal disease (ESRD) that might contribute to increase DNA damage. ESRD patients present increased circulating cell-free DNA (cfDNA) and different types of DNA injury. The underlying inflammatory process in ESRD may be associated with increased genomic damage and cfDNA contributing to further enhance inflammation. We analyzed the degree of genomic damage in ESRD patients under hemodialysis therapy, using the comet assay and cfDNA quantification. ESRD patients presented significantly higher C-reactive protein (CRP) and cell damaged DNA. The cfDNA correlated with age and inflammatory stage. Nine out of 39 patients died during the one year follow-up period and presented significantly higher cfDNA, than those who persisted alive. At lower CRP values, the increased DNA damage is still within the cell, and at higher CRP the damaged DNA is released in to plasma. The higher degree of genomic damage in ESRD might be a consequence of inflammation and aging, and may contribute to increase cancer and cardiovascular mortality risk. Our data suggest that the comet assay is more sensitive for low-grade inflammatory conditions, while cfDNA appears as a good biomarker for more severe inflammatory conditions, and as a biomarker for the outcome of ESRD patients.
Part of the book: Genotoxicity
Red blood cells (RBCs) are continuously exposed to oxidative stress (OS), mainly due to their primary function as oxygen carriers. Since RBC is a unique cell, without nucleus or other organelles, it presents a very special metabolism and a highly efficient antioxidant system to face OS conditions. Hemoglobin and RBC membrane are the major targets of oxidative modifications when RBC antioxidant capacity is overwhelmed. Fortunately, non-enzymatic agents, such as glutathione, and enzymatic agents, namely, several peroxidases, such as catalase, glutathione peroxidase and peroxiredoxin 2, are able to prevent OS damage. Although these peroxidases are mainly cytosolic enzymes, evidence exists about their association to the RBC membrane. So far, it appears that the relative importance of the three enzymes is related to hydrogen peroxide levels within the RBC. In this chapter, we will focus on the importance of these peroxidases in the RBC’s defense against OS mainly in the RBC cytosol and also the interplay between them and the RBC membrane. The potential role of their binding to the membrane will also be addressed.
Part of the book: Erythrocyte