Role of iron deficiency and anemia in cardio-renal syndromes.
ABSTRACT Chronic heart failure is a common disorder associated with unacceptably high mortality rates. Chronic renal disease and anemia are two important comorbidities that significantly influence morbidity and mortality in patients with chronic heart failure (CHF). Progress in CHF again may cause worsening of kidney function and anemia. To describe this vicious cycle, the term cardio-renal anemia syndrome has been suggested. Iron deficiency is part of the pathophysiology of anemia in both CHF and chronic kidney disease, which makes it an interesting target for treatment of anemia in cardio-renal anemia syndrome. Recently, studies have highlighted the potential clinical benefits of treating iron deficiency in patients with CHF, even if these patients are nonanemic. This article summarizes studies investigating the influence of iron deficiency with or without anemia in chronic kidney disease and CHF and gives an overview of preparations of intravenous iron currently available.
Article: Frailty and heart disease.[Show abstract] [Hide abstract]
ABSTRACT: Frailty is emerging as a syndrome of pre-disability that can identify persons at risk for negative outcomes. Its presence places the individual at risk for rapid deterioration when a major event such as myocardial infarction or hospitalization occurs. In patients with cardiovascular disease, frailty is about three times more prevalent than among elderly persons without. Screening for frailty in heart disease is important not only because of its prognostic value, but also because a variety of therapeutic interventions are available.International journal of cardiology 08/2013; · 6.18 Impact Factor
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ABSTRACT: Anemia in end-stage renal disease (ESRD) results mainly from erythropoietin and iron deficiency. Anemia could be confounded, however, by accelerated clearance of circulating erythrocytes because of premature suicidal erythrocyte death or eryptosis characterized by phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increased cytosolic Ca(2+) concentration ([Ca(2+)]i), oxidative stress, and ceramide. The present study explored whether and how ESRD influences eryptosis. Blood was drawn from healthy volunteers (n = 20) as well as ESRD patients (n = 20) prior to and after hemodialysis. Phosphatidylserine exposure was estimated from annexin V binding, [Ca(2+)]i from Fluo3-fluorescence, reactive oxygen species (ROS) from 2',7'dichlorodihydrofluorescein fluorescence, and ceramide from fluorescein-isothiocyanate-conjugated antibody binding in flow cytometry. Measurements were made in erythrocytes from freshly drawn blood and in erythrocytes from healthy volunteers exposed in vitro for 24 h to plasma from healthy volunteers or ESRD patients prior to and following dialysis. The patients suffered from anemia (hemoglobin 10.1 ± 0.5 g/100 ml) despite 1.96 ± 0.34 % reticulocytes. The percentage of phosphatidylserine-exposing erythrocytes was significantly higher in ESRD patients (0.84 ± 0.09 %) than in healthy volunteers (0.43 ± 0.04 %) and was significantly increased immediately after dialysis (1.35 ± 0.13 %). The increase in phosphatidylserine exposure was paralleled by increase in [Ca(2+)]i, oxidative stress, and ceramide abundance. As compared to addition of plasma from healthy individuals, addition of predialytic but not of postdialytic plasma from ESRD patients increased phosphatidylserine exposure, [Ca(2+)]i, ROS, and ceramide abundance. In conclusion, both, dialyzable components of uremic plasma and dialysis procedure, trigger eryptosis at least in part by increasing erythrocyte [Ca(2+)]i, ROS, and ceramide formation. Anemia in uremia results in part from eryptosis, the suicidal erythrocyte death. Eryptosis in uremia is triggered in part by a dialyzable plasma component. Eryptosis in uremia is further triggered by dialysis procedure. Eryptosis in uremia is in part due to increased cytosolic Ca(2+) concentration. Eryptosis in uremia is further due to oxidative stress and ceramide formation.Journal of Molecular Medicine 04/2014; · 4.77 Impact Factor
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ABSTRACT: Significance: Eryptosis, the suicidal erythrocyte death, is characterized by cell shrinkage, membrane blebbing and phosphatidylserine translocation to the outer membrane leaflet. Phosphatidylserine at the erythrocyte surface binds endothelial CXCL16/SR-PSOX (CXC-Motiv-Chemokin-16/Scavenger-receptor-for-phosphatidylserine-and-oxidized-low-density-lipoprotein) and fosters engulfment of affected erythrocytes by phagocytosing cells. Eryptosis serves to eliminate infected or defective erythrocytes, but excessive eryptosis may lead to anemia and may interfere with microcirculation. Clinical conditions with excessive eryptosis include diabetes, chronic renal insufficiency, hemolytic uremic syndrome, sepsis, malaria, iron deficiency, sickle cell anemia, thalassemia, glucose 6-phosphate dehydrogenase deficiency, glutamate cysteine ligase modulator deficiency, and Wilson´s disease. Recent advances: Eryptosis is triggered by a wide variety of xenobiotics and other injuries such as oxidative stress. Signaling of eryptosis includes prostaglandin E2 formation with subsequent activation of Ca2+-permeable cation channels, Ca2+ entry, activation of Ca2+-sensitive K+ channels and cell membrane scrambling, as well as phospholipase A2 stimulation with release of platelet-activating factor, sphingomyelinase activation and ceramide formation. Eryptosis may involve stimulation of caspases and calpain with subsequent degradation of the cytoskeleton. It is regulated by AMP-activated kinase, cGMP-dependent protein kinase, Janus-activated kinase 3, casein kinase 1α, p38 kinase and p21-activated kinase 2. It is inhibited by erythropoietin, antioxidants and further small molecules. Critical issues: It remains uncertain for most disorders whether eryptosis is rather beneficial because it precedes and thus prevents hemolysis or whether it is harmful because of induction of anemia and impairment of microcirculation. Future directions will address the significance of eryptosis, mechanisms underlying eryptosis, and pharmacological tools fostering or inhibiting eryptosis.Antioxidants & Redox Signaling 12/2013; · 8.20 Impact Factor