cardiovascular-agents and Cardio-Renal-Syndrome

Patients in the intensive care unit often suffer from cardiorenal syndrome, which can have an important influence on the patient's outcome. The heart and kidney influence each other via organ crosstalk. We screened and evaluated current publications on cardiorenal syndromes and their therapy. A key role in the management of cardiorenal syndromes is renal decongestion via loop diuretics.

Topics: Cardio-Renal Syndrome; Cardiovascular Agents; Combined Modality Therapy; Diuretics; Humans; Renal Agents

The treatment of cardiorenal syndrome is as complex as the various mechanisms underlying its pathophysiology. Randomized controlled data typically focus on the treatment of heart failure with cardiac specific endpoints and a lack of worsening renal function used as a surrogate for efficacy. When heart failure is considered the inciting event, the acute state is managed with vasodilators, inotropic support, and decongestion; whereas neurohormonal axis inhibition is more commonly applied to chronic state. A recent shift in thought process regarding the interplay of cardiac and renal dysfunction suggests that renal congestion may be the primary driver of worsening renal function.

Topics: Cardio-Renal Syndrome; Cardiovascular Agents; Hemodynamics; Humans; Peritoneal Dialysis; Vasodilator Agents

The development and progression of cardiovascular disease (CVD) and renal disorders are very closely related. In patients with chronic kidney disease (CKD), therapies proven to protect the cardiovascular and renal systems simultaneously are generally used only at low doses or not at all. In particular, patients with CKD who receive angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or mineralocorticoid-receptor antagonists (MRAs) often do not experience complete blockade of the renin-angiotensin-aldosterone system, primarily owing to the risk of hyperkalaemia. In this Review, we provide an overview of the available treatments required for adequate cardiorenal protection in patients with CKD. Drugs such as β-blockers that interfere with renin secretion will be discussed, in addition to agents that can prevent hyperkalaemia, such as potassium binders and nonsteroidal MRAs. Furthermore, the current literature on the role of statins, in addition to new compounds and dosing recommendations for the treatment of patients with CKD will also be reviewed. Further studies with these new compounds and doses are needed to ascertain whether these approaches can improve the long-term cardiovascular and renal prognosis in patients with CKD.

Topics: Cardio-Renal Syndrome; Cardiovascular Agents; Cardiovascular Diseases; Humans; Renal Agents; Renal Insufficiency, Chronic; Renin-Angiotensin System; Risk Factors; Treatment Outcome

Renal dysfunction is a frequent finding in patients with acute heart failure (AHF) and an important prognostic factor for adverse outcomes. Worsening of renal function occurs in 30-50% of patients hospitalised for AHF, and is associated with increased mortality, prolonged hospital stay and increased risk of readmission. Likely mechanisms involved in the decrease in renal function include impaired haemodynamics and activation of neurohormonal factors, such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine-vasopressin system. Additionally, many drugs currently used to treat AHF have a detrimental effect on renal function. Therefore, pharmacotherapy for AHF should carefully take into account any potential complications related to renal function. Serelaxin, currently in clinical development for the treatment of AHF is a recombinant form of human relaxin-2, identical in structure to the naturally occurring human relaxin-2 peptide hormone that mediates cardiac and renal adaptations during pregnancy. Data from both pre-clinical and clinical studies indicate a potentially beneficial effect of serelaxin on kidney function. In this review, we discuss the mechanisms and impact of impairment of renal function in AHF, and the potential benefits of new therapies, such as serelaxin, in this context.

Topics: Acute Disease; Animals; Cardio-Renal Syndrome; Cardiovascular Agents; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Humans; Kidney; Kidney Diseases; Recombinant Proteins; Relaxin; Treatment Outcome

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

Cardiorenal syndrome (CRS) is a condition in which there is a complex interrelationship between cardiovascular disease (CVD) and chronic kidney disease (CKD). Impairment of one organ could accelerate pathological processes in the other, which in turn accelerates the progression of failure of both. Although clinical studies hint at a specific bidirectional interaction between cardiovascular system and kidney, insight into the pathogenesis of CRS remains unknown. One possible factor that could explain this link is endothelial dysfunction (ED). ED is not only involved in initiation and progression of atherosclerosis, but also contributes to progression of renal injury. Asymmetric dimethylarginine (ADMA) is an endogenous NO synthase inhibitor found in the plasma and cells. Plasma ADMA levels are increased in CKD patients and known to be an independent biomarker and predictor for future cardiovascular events as well as the progression of CKD. These findings indicate that accumulated ADMA-mediated ED may play important roles in CRS in CKD patients. In this review, we discuss the roles of ADMA in the development of ED, especially focusing on its roles in CRS.

Topics: Animals; Arginine; Cardio-Renal Syndrome; Cardiovascular Agents; Drug Delivery Systems; Humans; Nitric Oxide Synthase

Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF.

Topics: Acute Disease; Anemia, Iron-Deficiency; Cardio-Renal Syndrome; Cardiovascular Agents; Comorbidity; Diabetes Complications; Diuretics; Heart Failure; Humans; Hyperglycemia; Hypoglycemic Agents; Iron; Noninvasive Ventilation; Oxygen Inhalation Therapy; Prognosis; Pulmonary Disease, Chronic Obstructive

Interactions between the heart and the kidneys are increasingly acknowledged among both cardiologists and nephrologists. The term cardiorenal syndrome now applies to the bidirectional nature of how disease in one organ system affects the function of the other organ system. Cardiovascular disease is a major threat to patients with chronic kidney disease, while renal dysfunction is prevalent in patients with cardiac disease and is a significant predictor of prognosis in cardiac patients. Still, renal patients with cardiac disease have largely been excluded from the clinical trials that have been the basis of modern cardiologic treatment. In this review, the current understanding of the pathophysiological mechanisms involved in the cardiorenal syndrome and potential therapeutic implications will be summarized from a nephrologist's point of view. Probably, fragile cardiorenal patients will benefit from an enhanced collaboration between cardiologists and nephrologists to secure the best treatment given under safe conditions.

Topics: Acute Disease; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arteriosclerosis; Biomarkers; Cardio-Renal Syndrome; Cardiovascular Agents; Chronic Disease; Diuretics; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Risk Factors

Chronic kidney disease (CKD) significantly increases cardiovascular morbidity and mortality. CKD remains an under-represented population in cardiovascular clinical trials, and cardiovascular disease is an under-treated entity in CKD. Traditional cardiovascular risk factors in conjunction with uremia-related complications often progress to myocardial dysfunction. Such uremic cardiomyopathy leads to over-activation of neurohormonal pathways with detrimental effects. Management of the reno-cardiac syndrome (RCS) requires the targeting of these multiple facets. In this article we discuss the relevant pathophysiology of RCS, and present the clinical data related to its management.

Topics: Cardio-Renal Syndrome; Cardiovascular Agents; Chronic Disease; Humans; Renal Replacement Therapy; Renin-Angiotensin System; Risk Factors

One third of heart failure admissions may be complicated by acute kidney injury, resulting in a three-fold increase in length of stay and a greater likelihood of rehospitalization. Cardio-Renal syndrome type 1 refers to acute decompensation of cardiac function leading to acute renal failure. It often complicates acute coronary syndrome and acute decompensated heart failure. Both components of the syndrome contribute to morbidity and mortality. The pathophysiology of renal dysfunction is complex. Reduced cardiac output, passive congestion of the kidneys, and increased intra-abdominal pressure may contribute to the disorder. The heart, kidneys, renin-angiotensin system, sympathetic nervous system, immune system, and vasculature interact through intricate feedback loops. An imbalance in this complex system often will cause deterioration in both cardiac and renal function. Appreciation of these interactions is crucial to understanding the overall burden of disease, as well as its natural history, risk factors, associated morbidity and mortality, and therapeutic implications.

Topics: Acute Disease; Acute Kidney Injury; Cardio-Renal Syndrome; Cardiovascular Agents; Diuretics; Heart Failure; Humans; Renin-Angiotensin System

Cardiac and kidney disease are becoming increasingly more prevalent in the population, and may exist concurrently. One of the most important comorbidities in heart failure is renal dysfunction. The pathophysiology of cardio-renal syndromes is complicated, and has been divided into five categories. Cardio-Renal syndrome type 2 is described by chronic cardiac abnormalities resulting in impaired renal function. It is important to recognize this entity and to understand the pathophysiology underlying the cardiac and renal disorders to distinguish best treatment practices. The success in improved outcomes lies in optimization of heart failure therapies.

Topics: Cardio-Renal Syndrome; Cardiovascular Agents; Diuretics; Heart Failure; Humans; Renal Dialysis; Renal Insufficiency, Chronic

Cardio-renal syndrome (CRS) is a renal dysfunction occurring in a large percentage of patients hospitalized with congestive heart failure (HF). Cardiac and renal dysfunctions often occur simultaneously because they share causes and pathogenetic mechanisms. Current therapies for HF are focused on improving myocardial function and hemodynamic balance, but may have potential consequences for worsening renal function. The lack of specific trials in this field highlights the need for further studies aimed to assess efficacy and safety, titration and appropriate dosages of drugs, according to the etiology and severity of both myocardial and renal dysfunction. Moreover, the most recent clinical trials evaluating new drugs on clinical and renal outcome in acute heart failure syndromes (AHFS) failed to demonstrate an improvement in renal function and perfusion. In this context, several questions regarding the priority of drugs, their recommended dosage and potential adverse effects on cardiac and renal outcome need to be addressed. Although clinical guidelines for managing both HF and chronic kidney disease (CKD) have been drawn, until now agreed guidelines about patients with cardio-renal and reno-cardiac syndromes are lacking. Future treatment directions should take into consideration both kidney and heart function. Only this comprehensive approach might lead to an improvement in the management and outcomes of patients affected by CRS.

Topics: Acute Disease; Cardio-Renal Syndrome; Cardiovascular Agents; Cardiovascular System; Chronic Disease; Clinical Trials as Topic; Disease Management; Disease Progression; Drug Dosage Calculations; Drug Monitoring; Early Diagnosis; Hemodynamics; Humans; Kidney; Practice Guidelines as Topic

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Topics: Biomarkers; Cardio-Renal Syndrome; Cardiovascular Agents; Contrast Media; Diuretics; Gene-Environment Interaction; Heart; Humans; Kidney; Renal Blood Flow, Effective; Renin-Angiotensin System; Risk Factors; Shock; Terminology as Topic

Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcome in terms of cardiovascular morbidity and mortality while chronic heart failure may cause CKD. All these disorders contribute to the composite definition of cardio-renal syndromes. Renal impairment in HF patients has been increasingly recognized as an independent risk factor for morbidity and mortality; however, the most important clinical trials in HF tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in HF are not known, and several pathways could contribute to the "vicious heart/kidney circle." Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin-aldosterone pathways and arginine-vasopressin release. All these mechanisms cause fluid and sodium retention, peripheral vasoconstriction and an increased congestion as well as cardiac workload. Therapy addressed to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardio-renal syndrome.

Topics: Biomarkers; Cardiac Output; Cardio-Renal Syndrome; Cardiovascular Agents; Disease Progression; Diuretics; Heart; Humans; Interdisciplinary Communication; Kidney; Kidney Function Tests; Medication Therapy Management; Patient Selection; Renal Blood Flow, Effective; Renin-Angiotensin System; Risk Factors; Shock; Water-Electrolyte Imbalance

Cardiorenal syndrome (CRS) is a group of disorders in which heart or kidney dysfunction worsens each other. This study aimed to explore the improvement effect of nicorandil on cardiorenal injury in patients with type I CRS. Patients with coronary heart disease complicated with type I CRS were enrolled. Based on the conventional treatment, the patients were prospectively randomized into a conventional treatment group and a nicorandil group, which was treated with 24 mg/d nicorandil intravenously for 1 week. Fasting peripheral venous blood serum and urine were collected before and at the end of treatment. An automatic biochemical analyzer and enzyme linked immunosorbent assay were used to detect B-type brain natriuretic peptide (BNP), serum creatinine (Scr) and cystatin C (Cys-C), renal injury index-kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) levels. The left ventricular ejection fraction was measured by echocardiography. All measurements were not significantly different between the nicorandil and conventional treatment groups before treatment (all P > 0.05), and BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were decreased in the 2 groups at the end of treatment (all P < 0.05). Compared with the conventional treatment group, BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were more significantly decreased in the nicorandil group (all P < 0.05) and left ventricular ejection fraction was more significantly increased (P < 0.05). Therefore, nicorandil could significantly improve the cardiac and renal function of patients with type I CRS. This may prove to be a new therapeutic tool for improving the prognosis and rehabilitation of type I CRS.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardio-Renal Syndrome; Cardiovascular Agents; China; Coronary Disease; Creatinine; Cystatin C; Female; Functional Status; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-18; Kidney; Lipocalin-2; Male; Middle Aged; Natriuretic Peptide, Brain; Nicorandil; Prospective Studies; Recovery of Function; Time Factors; Treatment Outcome; Ventricular Function, Left

Cardiorenal syndrome (CRS) remains the leading cause of death in hospitalized patients for all disease entities. Sacubitril/Valsartan (Sac/Val) therapy has been proved to improve prognostic outcome in patients with heart failure or chronic kidney disease. This study tested the hypothesis that combined levosimendan and Sac/Val was superior to just one therapy on protecting the heart and kidney against simultaneous heart and kidney ischemia (I) (for 50-min)-reperfusion (R) (for 7-days) (i.e., double IR) injury (defined as CRS).. Adult-male Spraque-Dawley rats (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (double IR), group 3 [double IR+levosimendan (10 mg/kg by intra-peritoneum administration at 30 min/followed by days 1-5 once daily after IR procedure)], group 4 [double IR+Sac/Val (10 mg/kg, orally at 30 min/followed by days 1-5 twice daily after IR procedure)], and group 5 (double IR+Sac/Val+levosimendan). By day 7 after double-IR, the left-ventricular-ejection fraction (LVEF)/left-ventricular-fraction-shortening (LVFS) were highest in group 1, lowest in group 2 and significantly higher in group 5 than in groups 3/4, but they showed no difference between groups 3/4, whereas the circulatory heart-failure (brain-natriuretic peptide)/proinflammatory (suppression of tumorigenicity-2) biomarkers, blood-urea-nitrogen/creatinine and ratio of urine protein to creatinine (all p < 0.0001) exhibited an opposite pattern of LVEF among the groups. The protein expressions of inflammatory (tumor necrosis factor-α/interleukin-1ß/matrix metalloproteinase-9)/oxidative-stress (NOX-1/NOX-2/NOX-4)/apoptotic (mitochondrial-Bax/caspase-3/poly-(ADP-ribose)-polymerase)/fibrotic (Smad3/transforming growth factor-ß)/mitochondrial-damaged (cytosolic-cytochrome-C)/myocardial-hypertrophic (ß-MHC) biomarkers in LV myocardium exhibited an opposite pattern of LVEF among the groups (all p < 0.0001). The cellular expressions of inflammatory (CD68)/DNA-damaged (γ-H2AX) biomarkers and infarct/fibrotic areas in LV myocardium and kidney displayed an opposite pattern of LVEF among the groups (all p < 0.0001).. Combined levosimendan and Sac/Val was superior to merely one therapy on protecting the heart and kidney as well as preserving their functions against double IR injury.

Topics: Aminobutyrates; Animals; Apoptosis; Biphenyl Compounds; Cardio-Renal Syndrome; Cardiovascular Agents; Drug Combinations; Fibrosis; Humans; Inflammation; Kidney; Male; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Simendan; Stroke Volume; Valsartan; Ventricular Function, Left

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

Patients with chronic kidney diseases (CKDs) and cardiovascular diseases (CVDs) present with various degree of anemia. Anemia has been associated with poor outcome in patients with CKD and CVD. CVD is the commonest cause of morbidity and mortality in patients with CKD. CKD causes anemia and CVD, and this rapidly deteriorates when anemia is not corrected. This triad of CVD, CKD, and anemia has been termed cardio-renal-anemia syndrome. The objective of this study is to highlight the importance of cardio-renal-anemia syndrome, their relationship, and management. Three patients with various stages of CKD who presented with anemia and cardiovascular abnormalities are reported. The patients responded well to various interventional measures, with improvement in their clinical and laboratory parameters. Cardio-renal-anemia syndrome is an entity that should be identified. Early and appropriate intervention leads to better outcome.

Topics: Adult; Aged; Anemia; Cardio-Renal Syndrome; Cardiovascular Agents; Combined Modality Therapy; Comorbidity; Diuretics; Erythrocyte Transfusion; Female; Hematinics; Humans; Male; Middle Aged; Predictive Value of Tests; Renal Dialysis; Treatment Outcome