losartan-potassium and Cardio-Renal-Syndrome

The association between chronic kidney disease (CKD) and cardiovascular disease (CVD) is well established, and there is mounting evidence of interorgan cross talk that may accelerate pathologic processes and the progression of organ dysfunction in both systems. This process, termed cardiorenal syndrome (CRS) by the Acute Dialysis Quality Initiative, is considered a major health problem: patients with CKD and CVD are at much higher risk of mortality than patients with either condition alone. To date, the majority of CRS research has focused on neurohormonal mechanisms and hemodynamic alterations. However, mounting evidence suggests that abnormalities in the normal pathophysiology of the bone-mineral axis, iron, and erythropoietin play a role in accelerating CKD and CVD. The goal of this article is to review the role and interrelated effects of the bone-mineral axis and anemia in the pathogenesis of chronic CRS.

Topics: Anemia; Bone and Bones; Calcifediol; Calcitriol; Calcium; Cardio-Renal Syndrome; Cardiovascular Diseases; Erythropoietin; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Iron; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic

A highly complex interplay exists between the heart and kidney in the setting of both normal and abnormal physiology. In the context of heart failure, a pathophysiological condition termed the cardiorenal syndrome (CRS) exists whereby dysfunction in the heart or kidney can accelerate pathology in the other organ. The mechanisms that underpin CRS are complex, and include neuro-hormonal activation, oxidative stress and endothelial dysfunction. The endothelium plays a central role in the regulation of both cardiac and renal function, and as such impairments in endothelial function can lead to dysfunction of both these organs. In particular, reduced bioavailability of nitric oxide (NO) is a key pathophysiologic component of endothelial dysfunction. The synthesis of NO by the endothelium is critically dependent on the plasmalemmal transport of its substrate, L-arginine, via the cationic amino acid transporter-1 (CAT1). Impaired L-arginine-NO pathway activity has been demonstrated individually in heart and renal failure. Recent findings suggest abnormalities of the L-arginine-NO pathway also play a role in the pathogenesis of CRS and thus this pathway may represent a potential new target for the treatment of heart and renal failure.

Topics: Anti-Inflammatory Agents; Arginine; Biological Transport; Cardio-Renal Syndrome; Cardiovascular Agents; Cationic Amino Acid Transporter 1; Diuretics; Endothelium, Vascular; Erythropoietin; Heart; Hemodynamics; Humans; Inflammation Mediators; Kidney; Nitric Oxide; Oxidative Stress; Sympathetic Nervous System

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.

Topics: Anemia, Iron-Deficiency; Cardio-Renal Syndrome; Chronic Disease; Erythropoietin; Ferric Compounds; Hematinics; Humans; Iron

Cardio-renal-anemia syndrome is a combination of heart failure, kidney failure, and anemia. Many advanced chronic kidney disease patients have both anemia and chronic heart failure. They have often hyperhomocysteinemia, high dimethylarginine values and low erythropoietin levels. Nephrologists treat advanced chronic kidney disease patients with erythropoiesis stimulating agents to improve anemia, renal and heart disease. Erythropoiesis stimulating agents, though considered essential to improve anemia in chronic kidney disease patients, have shown no significant protective effect on cardiovascular disease when used in large clinical trials targeting normal hemoglobin levels. It is possible that the high amounts of these drugs, given to reach normal hemoglobin values, may have counterbalanced the positive effect on endothelium obtained with low doses. Many studies have shown that erythropoietin improves endothelial function in animals with high dimethylarginine levels, lowering asymmetric dimethylarginine and increasing nitric oxide synthesis. Advanced chronic kidney disease patients have also high homocysteine levels which further reduce endothelial function by increasing asymmetric dimethylarginine. Homocysteine-lowering vitamin B treatment has been associated to a significant reduction of cardiovascular disease in advanced chronic kidney disease patients. Low doses of epoetin and B vitamins may improve cardiovascular morbidity by reducing asymmetric dimethylarginine and by increasing nitric oxide synthase activity. This review analyses the interaction between erythropoietin, dimethylarginine and homocysteine, and their role in cardio-renal-anemia syndrome.

Topics: Anemia; Animals; Arginine; Cardio-Renal Syndrome; Erythropoietin; Homocysteine; Humans; Nitric Oxide Synthase; Vitamin B Complex

Cardiorenal anemia syndrome (CRAS) refers to the simultaneous presence of anemia, heart failure (HF), and chronic kidney disease (CKD) that forms a pathologic triad with an observe impact on morbidity and mortality. Certain researches were made regarding the usage of erythropoietin (EPO) in patients with the above mentioned disorders. This leads to the improvement of left ventricular function, quality of life and physical tolerance with decreased risk of hospitalization. Despite successful anemia treatment with EPO in dialysis patients with CKD, HF and cardiorenal syndrome type 2, it should be important to reveal the target Hb level and role of EPO in this category of patients. According to European guidelines in 85% of hemodialysis patients targeted Hb level should be no more than 11g/dl, moreover, the treatment of anemia can be organized before dialysis and it will certainly increase the quality of life in this type of patients.

Topics: Anemia; Cardio-Renal Syndrome; Erythropoietin; Heart Failure; Hospitalization; Humans; Kidney Failure, Chronic; Quality of Life; Renal Dialysis; Treatment Outcome; Ventricular Function, Left

We observed 93 patients with CRS 2,4,5 types having anemia, systolic dysfunction of left ventricle (LV) - EF ≤45% and heart failure functional class (FC) II-IV (NYHA). All patients are under HD and were treated with EPO 3 times per week in a period of 6 months. We revealed improvement of LV EF 4,3 % and HF FC after EPO treatment and concluded that EPO therapy causes regression of LV hypertrophy, improves LV function and quality of life.

Topics: Anemia; Cardio-Renal Syndrome; Drug Administration Schedule; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Quality of Life; Renal Dialysis; Treatment Outcome; Ventricular Function, Left

Combined heart and renal failure is associated with high cardiovascular morbidity and mortality. Anti-oxidant and anti-inflammatory, non-hematopoietic effects of erythropoietin (EPO) treatment have been proposed. Monocytes may act as biosensors of the systemic environment. We hypothesized that monocyte transcriptomes of patients with cardiorenal syndrome (CRS) reflect the pathophysiology of the CRS and respond to short-term EPO treatment at a recommended dose for treatment of renal anemia.. Patients with CRS and anemia (n = 18) included in the EPOCARES trial were matched to healthy controls (n = 12). Patients were randomized to receive 50 IU/kg/week EPO or not. RNA from CD14(+)-monocytes was subjected to genome wide expression analysis (Illumina) at baseline and 18 days (3 EPO injections) after enrolment. Transcriptomes from patients were compared to healthy controls and effect of EPO treatment was evaluated within patients.. In CRS patients, expression of 471 genes, including inflammation and oxidative stress related genes was different from healthy controls. Cluster analysis did not separate patients from healthy controls. The 6 patients with the highest hsCRP levels had more differentially expressed genes than the 6 patients with the lowest hsCRP levels. Analysis of the variation in log(2) ratios of all individual 18 patients indicated that 4 of the 18 patients were different from the controls, whereas the other 14 were quite similar. After short-term EPO treatment, every patient clustered to his or her own baseline transcriptome. Two week EPO administration only marginally affected expression profiles on average, however, individual gene responses were variable.. In stable, treated CRS patients with mild anemia, monocyte transcriptomes were modestly altered, and indicated imprints of inflammation and oxidative stress. EPO treatment with a fixed dose has hematopoietic effects, had no appreciable beneficial actions on monocyte transcription profiles, however, could also not be associated with undesirable transcriptional responses.

Topics: Aged; Anemia; Anti-Inflammatory Agents; Antioxidants; Biosensing Techniques; Cardio-Renal Syndrome; Cluster Analysis; DNA, Complementary; Erythropoietin; Female; Gene Expression Profiling; Heart Failure; Humans; Lipopolysaccharide Receptors; Male; Middle Aged; Monocytes; Oxidative Stress; Renal Insufficiency; Transcriptome

Atherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis.. The EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA).. MR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without.. ARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Atherosclerosis; Cardio-Renal Syndrome; Chi-Square Distribution; Contrast Media; Erythropoietin; Female; Fibrosis; Glomerular Filtration Rate; Heart Failure; Hematinics; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Meglumine; Middle Aged; Myocardium; Netherlands; Organometallic Compounds; Predictive Value of Tests; Prevalence; Prognosis; Renal Artery; Renal Artery Obstruction; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

Chronic kidney disease (CKD) and anemia are common in patients with heart failure (HF) - these 3 conditions have been coined the Cardiorenal Anemia Sydrome (CRAS). The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) guidelines do not specifically address patients with CRAS, creating uncertainty in erythropoietin (EPO) prescribing. We sought to determine predictors of EPO use in patients with CRAS.. We conducted a retrospective cohort study at the Veteran's Affairs Greater Los Angeles Healthcare System (VAGLAHS), a 300+ bed facility that provides primary and tertiary inpatient, and ambulatory care services, between January 1, 2003 to December 31, 2006. A multiple logistic regression model was constructed to identify predictors of EPO use among CRAS patients.. Of 2058 patients with CRAS, 213 (10.3%) were prescribed EPO. There were significant differences in baseline characteristics between the EPO and non-EPO groups. The following predictors were found to be associated with EPO prescription: iron supplementation (odds ratio [OR] 52.70, 95% confidence interval [CI] 11.70-237.46), renal clinic appointment (OR 2.60, 95% CI 1.79-3.76), malignancy (OR 1.52, 95% CI 1.07-2.16) and use of hydralazine/nitrates (OR 1.41, 95% CI 1.03-1.92). There was an inverse association found between EPO prescription and baseline hemoglobin (OR 0.61, 95% CI 0.53-0.70) and eGFR (OR 0.96, 95% CI 0.94-0.97).. A small proportion of patients eligible for EPO therapy according to guidelines at the time of the study were prescribed the indicated therapy. Markers of declining renal function or those suggesting need for anemia therapy were identified as EPO predictors.

Topics: Aged; Anemia; Cardio-Renal Syndrome; Cohort Studies; Erythropoietin; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Retrospective Studies

Patients with chronic kidney disease (CKD) frequently suffer from heart disease as well. The combination of the two processes can exacerbate inflammation, resulting in increases in both resistance to erythropoietin (EPO) and mortality.. The aim of this study was to determine the prevalence of heart disease in a representative group of non-dialysis patients with stage 4-5 CKD, and the influence of that entity on EPO requirements and on mortality during a period of 36 months.. 134 patients (68% on EPO at the beginning, increasing to 72.3% during follow-up) were monitored for 36 months. To evaluate the dose-response effect of EPO therapy, we used the erythropoietin resistance index (ERI) calculated as the weekly weight-adjusted dose of EPO divided by the haemoglobin level. The ERI was determined both initially and during the last six months before the end of the study.. 39 patients (29.1%) had history of heart disease; 22 (16.4%) had suffered from heart failure (HF). The ERI was higher in patients with a history of heart disease or HF and those treated with drugs acting on the renin-angiotensin system (ACE inhibitors or ARBs). Using ERI as the dependent variable in the multivariate analysis, the variables that composed the final model were ferritin, haemoglobin, glomerular filtration rate and history of HF. The 36 month mortality rate (n=39 patients) was higher in the group having ERI above the median (2.6IU/week/kg/gram of haemoglobin in 100ml) (P=.002), and in the groups with heart disease (P=.001) or HF (P=.001) according to the Kaplan-Meier survival analysis.. Patients with history of heart disease or HF have a higher ERI, and all of these characteristics are associated with lower survival. ERI can be considered a marker for risk of death in the short to-medium term.

Topics: Aged; Aged, 80 and over; Anemia; Autoimmune Diseases; Cardio-Renal Syndrome; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Resistance; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Heart Diseases; Heart Failure; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Severity of Illness Index