natriuretic-peptide--brain and Cardio-Renal-Syndrome

Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.

Topics: Acute Disease; Body Fluids; Cardio-Renal Syndrome; Cardiotoxins; Comorbidity; Heart Failure; Hospitalization; Humans; Inflammation Mediators; Myocardial Contraction; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Renin-Angiotensin System; Symptom Assessment; Vascular Resistance; Vasoconstriction; Vasodilator Agents

Acute decompensated heart failure is a common cause of hospitalization with worsening kidney function or acute kidney injury often complicating the admission, which can result in further dysfunction of both systems in the form of a cardiorenal syndrome. Therapy in this arena has been largely empiric as rigorous clinical trial data to inform therapeutic choices are lacking. Here we review and discuss the available clinical evidence for common approaches to the management of this condition. A multidisciplinary approach to the care of patients with cardiorenal syndrome that relies on the experience of nephrologists and cardiologists to individualize treatment is critical given the paucity of rigorous clinical trial data.

Topics: Cardio-Renal Syndrome; Diuretics; Hemofiltration; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Vasodilator Agents

Biomarkers are increaingly being used in the management of heart failure not only for the purpose of screening, diagnosis, and risk stratification, but also as a guide to evaluate the response to treatment in the individual patient and as an entry criterion and/or a surrogate marker of efficacy in clinical trials testing novel drugs. In this chapter, we review the role of established biomarkers for heart failure management, according to the main classification of HF phenotypes, based on the measurement of left ventricular ejection fraction, including heart failure with reduced (<40%), preserved (≥50%), and, as recently proposed, mid-range (40-49%) ejection fraction.

Topics: Adrenomedullin; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; beta-N-Acetyl-Galactosaminidase; Biomarkers; C-Reactive Protein; Cardio-Renal Syndrome; Catecholamines; Chromogranin A; Creatinine; Galectin 3; Glycopeptides; Growth Differentiation Factor 15; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-1; Interleukin-1 Receptor-Like 1 Protein; Interleukin-18; Interleukin-6; Lipocalin-2; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Renin; Renin-Angiotensin System; Stroke Volume; Troponin; Troponin T; Tumor Necrosis Factor-alpha

The interdependent damage to the heart and kidney organ systems is defined as cardiorenal syndrome, a complex\ pathophysiological disorder of the heart and kidney in which acute or chronic dysfunction of one organ can lead to acute\ or chronic damage to the other. Identification and early diagnosis of some subtypes of cardiorenal syndrome very often\ begin at family physician office, however, the use of simple and reliable diagnostic procedures such as MICE score using\ ECG and biomarkers has not been implemented yet. The clinical picture, diagnosis and treatment vary according to the 5\ cardiorenal syndrome subtypes, as described herein. Rational diagnosis of heart failure at family medicine office should\ include biomarkers (BNP and NT-pro BNP) before performing ultrasound of the heart, while for kidneys creatinine and\ estimated glomerular filtration rate are still in use, but not cysteine C and NGAL. Diagnostic procedure for suspected heart\ failure at family medicine office should include kidney function estimate and vice versa. Access to treatment of cardiorenal\ syndrome differs depending on the specialty to which the patient is referred first, i.e. consultant examination, cardiologist\ or nephrologist. A multidisciplinary approach to treatment of cardiorenal syndrome is still lacking.

Topics: Acute Disease; Cardio-Renal Syndrome; Disease Progression; Early Diagnosis; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Acute kidney injury is a frequent complication of acute heart failure syndromes, portending an adverse prognosis. Acute cardiorenal syndrome represents a unique form of acute kidney injury specific to acute heart failure syndromes. The pathophysiology of acute cardiorenal syndrome involves renal venous congestion, ineffective forward flow, and impaired renal autoregulation caused by neurohormonal activation. Biomarkers reflecting different aspects of acute cardiorenal syndrome pathophysiology may allow patient phenotyping to inform prognosis and treatment. Adjunctive vasoactive, neurohormonal, and diuretic therapies may relieve congestive symptoms and/or improve renal function, but no single therapy has been proved to reduce mortality in acute cardiorenal syndrome.

Topics: Acute Disease; Biomarkers; Cardio-Renal Syndrome; Cardiotonic Agents; Diuretics; Fluid Therapy; Glomerular Filtration Rate; Hemofiltration; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Vasodilator Agents

Unlike the prolonged benefit produced by the treatment of chronic heart failure, newer drugs tested for the treatment of acute heart failure in the last decade have failed to provide evidence of clinical benefit beyond some improvement in symptom relief. In particular, no drug has shown the ability to reduce the higher medium- and long-term risk of morbidity and mortality in these patients after an episode of decompensation. Current understanding of the pathophysiology of acute heart failure and its consequences has led to the hypothesis that, beyond symptom control, effective therapies for this syndrome should target not only the hemodynamic changes of the initial phase of the syndrome but should also "protect" the organism from the activation of neurohumoral and inflammatory pathways triggered by the decompensation episode, which persist in time and confer a risk of deleterious effects in several organs and tissues. Serelaxin, a new drug related to the peptidic endogenous hormones of the relaxin family, has recently been shown to provide multiple beneficial effects in terms of "organ protection" - not only in the cardiovascular and renal systems - from these acute heart failure-related deleterious changes. This drug has already been tested in acute heart failure patients with encouraging results in terms of medium-term clinical benefit, rendering serelaxin as a serious candidate for first-line, prognosis-modifying therapy in this syndrome.

Topics: Acute Disease; Amides; Benzazepines; Cardio-Renal Syndrome; Dobutamine; Fumarates; Heart Failure; Humans; Hydrazones; Inflammation; Kaplan-Meier Estimate; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Prognosis; Pyridazines; Randomized Controlled Trials as Topic; Recombinant Proteins; Relaxin; Simendan; Therapies, Investigational; Tolvaptan

Biomarkers have an increasingly important clinical role in managing patients with heart failure as well as those with kidney disease, both common conditions with generally poor prognostic outcomes and huge impacts on healthcare economics. For patients with chronic heart failure, biomarkers have become centre place in streamlining diagnostic pathways as well as identifying those with worse prognosis. There is much interest in the role for biomarkers in identifying patients at risk of acute kidney injury, although a number of these currently remain as research tools or are in the early stages of evaluation in clinical practice. Patients with cardiorenal syndrome represent a particular challenge to the clinician, and recent studies have suggested a valuable clinical role for certain biomarkers in this setting, either on their own or in combination. This paper will focus on biomarkers with a current clinical role in patients with cardiorenal disease (natriuretic peptides and neutrophil gelatinase-associated lipocalin), although brief reference will be made to other biomarkers with potential future application.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Biomarkers; Cardio-Renal Syndrome; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Failure, Chronic; Lipocalin-2; Lipocalins; Natriuretic Peptide, Brain; Natriuretic Peptides; Nursing Diagnosis; Peptide Fragments; Prognosis; Proto-Oncogene Proteins

Worsening renal function (WRF) during the treatment of acute decompensated heart failure (ADHF) occurs in up to a third of patients and is associated with worse survival. Venous congestion is increasingly being recognized as a key player associated with WRF in ADHF. Understanding the hemodynamic effects of venous congestion and the interplay between venous congestion and other pathophysiological factors such as raised abdominal pressure, endothelial cell activation, anemia/ iron deficiency, sympathetic overactivity, and stimulation of the renin-angiotensin-aldosterone system will help in devising effective management strategies. Early recognition of venous congestion through novel techniques such as bioimpedance measurements and remote monitoring of volume status combined with customized diuretic regimens may prevent venous congestion and perhaps avoid significant WRF.

Topics: Acute Disease; Animals; Biomarkers; Cardio-Renal Syndrome; Cytokines; Diuretics; Electric Impedance; Endothelium, Vascular; Hemodynamics; Humans; Hyperemia; Iron Deficiencies; Natriuretic Peptide, Brain; Renal Circulation; Renin-Angiotensin System

The cardio-renal syndromes (CRS) are the result of complex bidirectional organ cross-talk between the heart and kidney, with tremendous overlap of diseases such as coronary heart disease, heart failure (HF), and renal dysfunction in the same patient. Volume overload plays an important role in the pathophysiology of CRS. The appropriate treatment of overhydration, particularly in HF and in chronic kidney disease, has been associated with improved outcomes and blood pressure control. Clinical examination alone is often insufficient for accurate assessment of volume status because significant volume overload can exist even in the absence of peripheral or pulmonary edema on physical examination or radiography. Bioelectrical impedance techniques increasingly are being used in the management of patients with HF and those on chronic dialysis. These methods provide more objective estimates of volume status in such patients. Used in conjunction with standard clinical assessment and biomarkers such as the natriuretic peptides, bioimpedance analysis may be useful in guiding pharmacologic and ultrafiltration therapies and subsequently restoring such patients to a euvolemic or optivolemic state. In this article, we review the use of these techniques in CRS.

Topics: Acute Disease; Biomarkers; Blood Volume; Body Composition; Cardio-Renal Syndrome; Dielectric Spectroscopy; Electric Impedance; Heart Failure; Hemofiltration; Humans; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Water-Electrolyte Imbalance

Since the initial studies showing the usefulness of B-type natriuretic peptide for aiding in heart failure diagnosis, a vast number of other clinical applications for this neurohormone have emerged. In addition to refining our capabilities to diagnose and prognosticate in acute heart failure, natriuretic peptides are now being used in outpatient heart failure clinics, in screening programs, and in risk prediction algorithms in various settings. In just 10 years, B-type natriuretic peptide has gone from being an unknown biomarker to being one of the most useful in cardiology and beyond. In this perspective piece, the investigators review what we have learned about using natriuretic peptides over the past 10 years and the anticipated advances in their use over the next decade.

Topics: Acute Disease; Aftercare; Biomarkers; Cardio-Renal Syndrome; Dyspnea; Emergency Service, Hospital; Heart Failure; Humans; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment

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

Aim of the present study is to investigate the clinical efficacy of recombinant human brain natriuretic peptide (rhBNP) and dopamine combination treatment in patients with cardiorenal syndrome type 4 (CRS4) combined with hypotension. A total of 160 CRS4 patients admitted to our hospital from July 2010 to December 2014 were recruited, and were randomly divided into two groups, the observational group (n=80) and the control group (n=80). CRS4 patients treated with dopamine were recruited into the control group. Patients in the observational group were given rhBNP and dopamine combination treatment once every 8 h. Both groups received conventional treatments and the course of treatment was 7 days. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), serum creatinine (SCr), N-terminal brain natriuretic peptide precursor (Nt-proBNP), creatinine clearance (CCr), left ventricular end-diastolic diameter (LVEDd), left ventricular ejection fraction (LVEF), Stroke volume (SV), urine volume and adverse reactions before and after treatment were compared. The observational group showed significant changes in the levels of SBP, DBP and HR compared with the control group (P<0.05). The levels of SCr and Nt-proBNP decreased significantly in the observational group than those in the control group (P<0.05). The levels of CCr, LVEF, SV and urine volume increased significantly in the observational group than those in the control group (P<0.05). Patients in the observational group had mild and tolerable adverse reactions. rhBNP combined with dopamine infusion has good clinical efficacy and mild adverse effects in treatment of CRS4.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Cardio-Renal Syndrome; Dopamine; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Heart Rate; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Natriuretic Peptide, Brain; Recombinant Proteins; Recovery of Function; Time Factors; Treatment Outcome; Ventricular Function, Left

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD).. This randomized, controlled, phase II trial consisted of two parts. In part A, the safety and tolerability of oral BAY 94-8862 [2.5, 5, or 10 mg once daily (q.d.)] was assessed in 65 patients with HFrEF and mild CKD. In part B, BAY 94-8862 (2.5, 5, or 10 mg q.d., or 5 mg twice daily) was compared with placebo and open-label spironolactone (25 or 50 mg/day) in 392 patients with HFrEF and moderate CKD. BAY 94-8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone (0.04-0.30 and 0.45 mmol/L, respectively, P < 0.0001-0.0107) and lower incidences of hyperkalaemia (5.3 and 12.7%, respectively, P = 0.048) and WRF. BAY 94-8862 decreased the levels of B-type natriuretic peptide (BNP), amino-terminal proBNP, and albuminuria at least as much as spironolactone. Adverse events related to BAY 94-8862 were infrequent and mostly mild.. In patients with HFrEF and moderate CKD, BAY 94-8862 5-10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress, but it was associated with lower incidences of hyperkalaemia and WRF.

Topics: Administration, Oral; Aged; Albuminuria; Aldosterone; Blood Pressure; Cardio-Renal Syndrome; Creatinine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Male; Mineralocorticoid Receptor Antagonists; Naphthyridines; Natriuretic Peptide, Brain; Peptide Fragments; Potassium

Both heart and renal failure are characterised by increased systemic oxidative stress and endothelial dysfunction and occur in the cardiorenal syndrome (CRS). The aim of the present study was to assess the impact of N-acetylcysteine (NAC), a potent antioxidant, on endothelial function, B-type natriuretic peptide (BNP) and renal function in patients with CRS.. In a double blind, placebo controlled manner, we randomised nine stable outpatients with both heart failure (LVEF<40% and NYHA class II or III) and renal failure (Cockroft Gault clearance of 20-60ml/min) to placebo or NAC (500mg orally twice daily) for 28 days followed by a wash out period (>7 days) and crossover to the other treatment.. Eight patients completed the study and all data (N=9) was used in the analysis. Mean forearm blood flow improved significantly with NAC with mean ratio of improvement of 1.99 (SEM: ±0.49) for NAC and 0.73 (SEM: ±0.23) for placebo with a p-value of 0.047. There was no significant difference in BNP (p=0.25), renal function (p=0.71) or NYHA class (p=0.5). No deaths occurred during the trial.. In this pilot trial of patients with CRS, NAC therapy was associated with improved forearm blood flow. This may represent a general improvement in endothelial function and warrants further investigation of antioxidant therapy in these patients.

Topics: Acetylcysteine; Adolescent; Adult; Aged; Cardio-Renal Syndrome; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Female; Free Radical Scavengers; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects

Recombinant human brain natriuretic peptide (rhBNP) effects on type 4 cardiorenal syndrome (CRS) and adverse events such as heart failure rehospitalization and all-cause mortality have not been assessed in large-scale research. This study evaluated the impact of rhBNP on emergency dialysis and prognosis in end-stage renal disease (ESRD) patients with type 4 CRS, and the risk factors of emergency dialysis. This retrospective cohort study included patients with type 4 CRS and ESRD admitted for decompensated heart failure between January 2016 and December 2021. Patients were divided into the rhBNP and non-rhBNP cohorts, according to whether they were prescribed rhBNP. The primary outcomes were emergency dialysis at first admission and cardiovascular events within a month after discharge. A total of 77 patients were included in the rhBNP cohort (49 males and 28 females, median age 67) and 79 in the non-rhBNP cohort (47 males and 32 females, median age 68). After adjusting for age, residual renal function, and primary diseases, Cox regression analysis showed that rhBNP was associated with emergency dialysis (HR = 0.633, 95% CI 0.420-0.953) and cardiovascular events (HR = 0.410, 95% CI 0.159-0.958). In addition, multivariate logistic regression analysis showed that estimated glomerular filtration rate (eGFR) (OR = 0.782, 95% CI 0.667-0.917, P = 0.002) and procalcitonin (PCT) levels (OR = 1.788, 95% CI 1.193-2.680, P = 0.005) at the first visit were independent risk factors for emergency dialysis while using rhBNP was a protective factor for emergency dialysis (OR = 0.195, 95% CI 0.084-0.451, P < 0.001). This study suggests that RhBNP can improve cardiac function and reduce the occurrence of emergency dialysis and cardiovascular events in ESRD patients with type 4 CRS.

Topics: Aged; Cardio-Renal Syndrome; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Prognosis; Renal Dialysis; Retrospective Studies

This study aims to explore the effect of N-terminal pro-brain natriuretic peptide (NT-proBNP) variability (mean absolute difference of the log2 NT-proBNP level measured in hospital) on the prognosis of patients with cardiorenal syndrome (CRS) type 2. Patients with CRS type 2 were retrospectively included. The varied NT-proBNP indications were analyzed. They were NT-proBNP I(pre-treatment), NT-proBNP II(post-treatment), NT-proBNP II/I, ΔNT-proBNP, log2 (NT-proBNP) variability and mean log2 (NT-proBNP). A logistic regression model and survival curves (Kaplan-Meier analysis) were built to identify independent predictors associated with poor prognosis. The primary outcomes were major adverse renal and cardiac events. The secondary outcome was all-cause mortality. From 2012 to 2016, 136 patients were included in this study with 69 (50.7%) had high log2 (NT-proBNP) variability level. The optimal cutoff level for each NT-proBNP indication that predicts poor prognosis was calculated, and the area under curves ranged from 0.668 to 0.891 with different indications. Kaplan-Meier analysis revealed that there was significantly correlated with prevalence of primary outcomes and NT-proBNP variability. The hazard ratios (HRs) ranged from 1.67 to 6.61 with different indications. The multivariate regression analyses also identified the risk of the primary outcomes were associated with elevated NT-proBNP values, except NT-proBNP I. The odds ratio (ORs) ranged from 1.83 to 6.61 with different indications. When analyzing the relationship between NT-proBNP variability and all-cause mortality, the results were the same. NT-proBNP variability might serve as an independent predictor for poor prognosis and all-cause mortality in patients with CRS type 2.

Topics: Aged; Biomarkers; Cardio-Renal Syndrome; Female; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; ROC Curve

Chronic kidney disease (CKD) is a major contributor to the development of heart failure with preserved ejection fraction (HFpEF), whereas the underlying mechanism of cardiorenal HFpEF is still elusive. The aim of this study was to investigate the role of cardiac fibrosis in a rat model of cardiorenal HFpEF and explore whether treatment with Telmisartan, an inhibitor of renin-angiotensin-aldosterone system (RAAS), can ameliorate cardiac fibrosis and preserve diastolic function in cardiorenal HFpEF. Male rats were subjected to 5/6 subtotal nephrectomy (SNX) or sham operation (Sham), and rats were allowed four weeks to recover and form a stable condition of CKD. Telmisartan or vehicle was then administered p.o. (8 mg/kg/d) for 12 weeks. Blood pressure, brain natriuretic peptide (BNP), echocardiography, and cardiac magnetic resonance imaging were acquired to evaluate cardiac structural and functional alterations. Histopathological staining, real-time polymerase chain reaction (PCR) and western blot were performed to evaluate cardiac remodeling. SNX rats showed an HFpEF phenotype with increased BNP, decreased early to late diastolic transmitral flow velocity (E/A) ratio, increased left ventricular (LV) hypertrophy and preserved ejection fraction (EF). Pathology revealed increased cardiac fibrosis in cardiorenal HFpEF rats compared with the Sham group, while chronic treatment with Telmisartan significantly decreased cardiac fibrosis, accompanied by reduced markers of fibrosis (collagen I and collagen III) and profibrotic cytokines (α-smooth muscle actin, transforming growth factor-β1, and connective tissue growth factor). In addition, myocardial inflammation was decreased after Telmisartan treatment, which was in a linear correlation with cardiac fibrosis. Telmisartan also reversed LV hypertrophy and E/A ratio, indicating that Telmisartan can improve LV remodeling and diastolic function in cardiorenal HFpEF. In conclusion, cardiac fibrosis is central to the pathology of cardiorenal HFpEF, and RAAS modulation with Telmisartan is capable of alleviating cardiac fibrosis and preserving diastolic dysfunction in this rat model.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Blood Flow Velocity; Blood Pressure; Cardio-Renal Syndrome; Diastole; Disease Models, Animal; Echocardiography; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Stroke Volume; Telmisartan; Ventricular Function, Left; Ventricular Remodeling

The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients.. Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model.. AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1-20.6) for AKI.. Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Biomarkers; Cardio-Renal Syndrome; Female; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Nitric Oxide; Oxidative Stress; Percutaneous Coronary Intervention; Predictive Value of Tests; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Troponin

Chronic heart failure may lead to chronic kidney disease. Previous studies suggest tubular markers N-acetyl-b-D-glucosaminidase (NAG) and Kidney-injury-molecule-1 (KIM-1) as potential markers for the cardiorenal syndrome (CRS). The prognostic value of NAG and KIM-1 regarding implantable cardioverter defibrillator (ICD) shock therapies is unknown.. We included 314 patients with an ICD and collected plasma and urine samples. Urine-values of NAG and KIM-1 got related to urinary creatinine. Outcomes of interest were sustained adequate shock therapies and a combined endpoint of all-cause mortality, rehospitalisation due to congestive heart failure and adequate shock therapies. Follow up time was 32 months (IQR 6-35 months).. KIM-1 and NAG were positively correlated with NT-proBNP (KIM-1: r = .34, P < .001; NAG: r = .47, P < .001). NAG was significantly elevated in patients with primary prevention compared with secondary prevention ICD indication (P = .003). According to Kaplan Meier analysis, NAG as well as NT-proBNP were significant predictors for adequate ICD shock therapies and for the combined endpoint (each P < .001). Elevated KIM-1 showed no significant differences (each P = n.s.). In multivariate cox regression analysis, NAG as well as NT-proBNP were both independent predictors for adequate ICD shock therapies as well as the combined endpoint, beside ejection fraction <35% (each P < .05). Diabetes, primary prevention ICD indication, coronary artery disease, eGFR and age were no significant predictors for both endpoints (each P = n.s.).. Similar to NT-proBNP, NAG showed promising value for overall prognostication in ICD patients. Especially, NAG seems to incorporate an additional prognostic value regarding occurrence of ICD shock therapies.

Topics: Acetylglucosaminidase; Adult; Aged; Arrhythmias, Cardiac; Biomarkers; Cardio-Renal Syndrome; Creatinine; Defibrillators, Implantable; Electric Countershock; Female; Hepatitis A Virus Cellular Receptor 1; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Survival Rate; Treatment Outcome

Acute declines in kidney function occur in approximately 20%-30% of patients with acute decompensated heart failure, but its significance is unclear, and the importance of its context is not known. This study aimed to determine the prognostic value of a decline in kidney function in the context of decongestion among patients admitted with acute decompensated heart failure.. Using data from patients enrolled in the Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome Study (CARRESS) and Diuretic Optimization Strategies Evaluation (DOSE) trials, we used multivariable Cox regression models to evaluate the association between decline in estimated glomerular filtration rate (eGFR) and change in N-terminal pro-b-type natriuretic peptide (NT-proBNP) with a composite outcome of death and rehospitalization, as well as testing for an interaction between the two.. Among 435 patients, in-hospital decline in eGFR was not significantly associated with death and rehospitalization (hazard ratio [HR] = 0.89 per 30% decline, 95% confidence interval [CI] 0.74, 1.07), whereas decline in NT-proBNP was associated with lower risk (HR = 0.69 per halving, 95% CI 0.58, 0.83). There was a significant interaction (P = 0.002 unadjusted; P = 0.03 adjusted) between decline in eGFR and change in NT-proBNP where a decline in eGFR was associated with better outcomes when NT-proBNP declined (HR = 0.78 per 30% decline in eGFR, 95% CI 0.61, 0.99), but not when NT-proBNP increased (HR = 0.99, 95% CI 0.76, 1.30).. Decline in kidney function during therapy for acute decompensated heart failure is associated with improved outcomes as long as NT-proBNP levels are decreasing as well, suggesting that incorporation of congestion biomarkers may aid clinical interpretation of eGFR declines.

Topics: Acute Disease; Aged; Aged, 80 and over; Cardio-Renal Syndrome; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency

Background Early detection for worsening renal function (WRF) is indispensable in patients with acute decompensated heart failure (HF). We tested the hypothesis that the difference in the circulating levels of each B-type or brain natriuretic peptide (BNP) molecular form is associated with the occurrence of WRF. Methods and Results Circulating levels of proBNP, the NT-proBNP (N-terminal proBNP), and total BNP (proBNP+mature BNP) were prospectively measured in patients with acute decompensated HF using specific and sensitive enzyme immunochemiluminescent assays. An estimated mature BNP (emBNP) concentration was calculated by subtracting proBNP levels from total BNP levels. WRF was defined as a >20% decrease in the estimated glomerular filtration rate during the hospitalization. One-way repeated-measures ANOVA was used to compare the changes of variables between the patients with and without WRF. In patients with acute decompensated HF (New York Heart Association class III-IV; 96%) hospitalized for HF, NT-proBNP levels did not differ during the hospitalization between patients with and without WRF (n=42 and 140, respectively). By contrast, emBNP levels were lower in patients with WRF than in those without WRF on day 3 after admission. NT-proBNP/emBNP molar ratios were elevated on day 3 after admission in the patients with WRF, before estimated glomerular filtration rate declined, but were unchanged in patients without WRF. On day 3 after hospital admission, NT-proBNP/emBNP ratios were strongly associated with percentage decreases in estimated glomerular filtration rate. Conclusions These findings suggest that elevation of NT-proBNP/emBNP ratio precedes WRF in patients with acute HF and can be a potentially useful biomarker for risk stratification of cardiorenal syndrome.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardio-Renal Syndrome; Cross-Sectional Studies; Disease Progression; Early Diagnosis; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Young Adult

Cardiorenal syndrome (CRS) has posed tremendous challenges in patient management, and the detection of serum biomarkers may provide opportunities for early diagnosis and effective treatment. Herein, we introduce a novel surface-enhanced Raman scattering (SERS)-based sandwich immunoassay platform to simultaneously detect cardiac troponin I (cTnI), N-terminal prohormone of brain natriuretic peptide (NT-ProBNP), and neutrophil gelatinase-associated lipocalin (NGAL) for the early diagnosis of CRS by using Raman reporter-molecule-labeled Ag-Au nanostars (Ag-Au NSs) as nanotags and a three-dimensional ordered macroporous (3DOM) Au-Ag-Au plasmonic array as substrate. The Ag-Au NSs prepared by galvanic replacement feature bimetallic composition and a multibranched structure so that high SERS stability and enhancement are exhibited. Meanwhile, a 3DOM Au-Ag-Au plasmonic array was fabricated through Au-assisted electrodeposition and was further covered by a protective Au layer; it is characterized by a large specific surface area and high homogeneity, serving as a "hot field". When the nanotags and substrate were combined, "hot spots" were generated from the plasmon near-field coupling, which greatly increased the SERS enhancement. The limits of detection (LODs) were 0.76, 0.53, and 0.41 fg mL

Topics: Antibodies, Immobilized; Biomarkers; Cardio-Renal Syndrome; Gold; Humans; Immunoassay; Limit of Detection; Lipocalin-2; Metal Nanoparticles; Natriuretic Peptide, Brain; Peptide Fragments; Silver; Spectrum Analysis, Raman; Troponin I

Cardiorenal syndrome comprises a heterogeneous group of disorders characterized by acute or chronic cardiac and renal dysfunction.. The purpose of this study was to determine the effect of cardiorenal status using a dual-marker strategy with amino-terminal pro-brain natriuretic peptide (NT-proBNP) and cystatin C on cardiac resynchronization therapy (CRT) outcomes.. In 92 patients (age 66 ± 13 years; 80% male; left ventricular ejection fraction 26% ± 7%), NT-proBNP and cystatin C levels were measured at CRT implantation and at 1 month. NT-proBNP >1000 pg/mL and cystatin C >1 mg/L were considered high. Baseline cardiorenal patients were defined as having high NT-proBNP and cystatin C. At 1 month, CRT patients were categorized as (1) irreversible cardiorenal if cystatin C was persistently high; (2) progressive cardiorenal with transition from low to high cystatin C; (3) reversible cardiorenal with transition from high to low cystatin C; and (4) "normal" with stable low cystatin C. Outcomes were 6-month clinical and echocardiographic CRT response and 2 -year major adverse cardiovascular event (MACE).. Compared to patients with low NT-proBNP and cystatin C, cardiorenal patients had >9-fold increase risk of CRT nonresponse (odds ratio uncompensated 9.0; compensated 36.4; both P ≤.004) and >6-fold risk of MACE (hazard ratio uncompensated 8.5; P = .005). Compared to "normal" and reversible patients (referent), irreversible patients had a 9-fold increase for CRT nonresponse (odds ratio 9.1; P <.001) and had >4-fold risk of MACE (adjusted hazard ratio 5.1; P <.001). Irreversible patients were most likely echocardiographic CRT nonresponders.. Cardiorenal status by NT-proBNP and cystatin C can identify high-risk CRT patients, and those with both elevated concentrations have worse prognosis.

Topics: Aged; Biomarkers; Cardiac Resynchronization Therapy; Cardio-Renal Syndrome; Cystatin C; Echocardiography; Female; Heart Failure; Humans; Kidney Function Tests; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Stroke Volume; Treatment Outcome; Ventricular Function, Left

To explore the diagnostic value of copeptin (CPP) in cardiorenal syndrome (CRS) in rats and the association between CPP and impairment of heart and kidney, 60 male SD rats were randomly divided into blank control group (CK group), kidney failure group (SNX group), heart failure group (MI group), and CRS group. Heart and kidney function and their histology changes in rats from each group were detected. The correlation between serum CPP and heart and kidney function indexes was performed with Pearson correlation analysis. The HE staining of heart and kidney showed that the tissue lesion was more severe in CRS group than in SNX group and MI group. There was a significant positive correlation between serum CPP and brain natriuretic peptide (BNP) (. 探讨和肽素对心肾综合征（CRS）大鼠的诊断价值及与心肾损害的关系。雄性SD大鼠按随机数字表法分为空白对照组（CK组）、肾衰竭组（SNX组）、心力衰竭组（MI组）、CRS组，每组15只。观察各组心肾功能及组织病理形态的改变，并对和肽素与心肾功能指标进行相关性分析。心肾组织HE染色结果显示病变严重程度为CRS组>SNX组>MI组。血清和肽素与B型利钠肽（BNP）呈显著正相关（

Topics: Animals; Cardio-Renal Syndrome; Creatinine; Glycopeptides; Heart Failure; Humans; Kidney; Male; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley

Cardiorenal syndrome (CRS) is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. CRS remains a major global health problem. Qiliqiangxin (QLQX) is a traditional Chinese herbs medication, which can improve cardiac function, urine volume, and subjective symptoms in patients with chronic heart failure. In the present study, we aim to investigate the role of QLQX in the treatment of CRS type I and the possible mechanism through establishment of a rat model of myocardial infarction. Rats in CRS-Q group were orally treated with QLQX daily for 2 weeks or 4 weeks, while in sham group and CRS-C group were treated with saline at the same time. Enzyme-linked immunosorbent assay (ELISA) analysis showed that QLQX significantly reduced the levels of angiotensin II (AngII), brain natriuretic peptides (BNP), creatinine (CRE), cystatin C (CysC), tumor necrosis factor (TNF)-α, interleukin (IL)-6, microalbuminuria (MAU), and neutrophil gelatinase-associated lipocalin (NGAL) in plasma induced by myocardial infarction. Western blot analysis showed that QLQX significantly reduced the expressions of AngII, non-phagocytic cell oxidase (NOX)2, and B-cell lymphoma (Bcl)2 associated X protein (Bax), and increased the expressions of Bcl2 and Angiotensin II Type 1 receptor (ATR) in the kidney as compared with the CRS-C group. Fluorescence microscopy showed that the content of reactive oxygen species (ROS) was significantly reduced in the kidney as compared with the CRS-C group. We also examined the apoptosis level in kidney by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, and the result showed that QLQX significantly reduced the apoptosis level in kidney induced by myocardial infarction. Taken together, we suggest that QLQX may be a potentially effective drug for the treatment of CRS by regulating inflammatory/oxidative stress signaling.

Topics: Albuminuria; Angiotensin II; Animals; Anti-Inflammatory Agents; Antioxidants; Cardio-Renal Syndrome; Creatinine; Cystatin C; Drugs, Chinese Herbal; Interleukin-6; Kidney; Male; Myocardial Infarction; NADPH Oxidase 2; Natriuretic Peptide, Brain; Oxidative Stress; Phytotherapy; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Signal Transduction; Tumor Necrosis Factor-alpha

Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Inflammation and oxidative stress seem to play a pivotal role in its pathophysiology. In this in vivo study, we examined the putative role of inflammation and humoral markers in the pathogenesis of the CRS type 1.. We enrolled 53 patients with acute heart failure (AHF); 17 of them developed AKI (CRS type 1). The cause of AKI was presumed to be related to cardiac dysfunction after having excluded other causes. We assessed the plasma levels of proinflammatory cytokines (TNF-α, IL-6, IL-18, sICAM, RANTES, GMCSF), oxidative stress marker (myeloperoxidase, MPO), brain natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in AHF and CRS type 1 patients.. We observed a significant increase in IL-6, IL-18, and MPO levels in CRS type 1 group compared to AHF (p < 0.001). We found higher NGAL at admission in the CRS type 1 group compared to the AHF group (p = 0.008) and a positive correlation between NGAL and IL-6 (Spearman's rho = 0.45, p = 0.003) and between IL-6 and BNP (Spearman's rho = 0.43, p = 0.004). We observed lower hemoglobin levels in CRS type 1 patients compared to AHF patients (p < 0.05) and inverse correlation between hemoglobin and cytokines (IL-6: Spearman's rho = -0.38, p = 0.005; IL-18: Spearman's rho = -0.32, p = 0.02).. Patients affected by CRS type 1 present increased levels of proinflammatory cytokines and oxidative stress markers, increased levels of tissue damage markers, and lower hemoglobin levels. All these factors may be implicated in the pathophysiology of CRS type 1 syndrome.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Cardio-Renal Syndrome; Cytokines; Heart Failure; Hemoglobins; Humans; Intercellular Signaling Peptides and Proteins; Lipocalin-2; Natriuretic Peptide, Brain; Oxidative Stress; Peroxidase; Receptors, Interleukin-6

Background Cardiorenal syndrome type 1 ( CRS 1) as a complication of acute myocardial infarction can lead to adverse outcomes, and a method for early detection is needed. This study investigated the individual and integrated effectiveness of amino-terminal pro-brain natriuretic peptide (Pro-BNP), estimated glomerular filtration rate (eGFR), and high-sensitivity C-reactive protein (CRP) as predictive factors for CRS 1 in patients with acute myocardial infarction. Methods and Results In a retrospective analysis of 2094 patients with acute myocardial infarction, risk factors for CRS 1 were analyzed by logistic regression. Receiver operating characteristic curves were constructed to determine the predictive ability of the biomarkers individually and in combination. Overall, 177 patients (8.45%) developed CRS 1 during hospitalization. On multivariable analysis, all 3 biomarkers were independent predictors of CRS 1 with odds radios and 95% confidence intervals for a 1-SD change of 1.792 (1.311-2.450) for log(amino-terminal pro-brain natriuretic peptide, 0.424 (0.310-0.576) for estimated glomerular filtration rate, and 1.429 (1.180-1.747) for high-sensitivity C-reactive peptide. After propensity score matching, the biomarkers individually and together significantly predicted CRS 1 with areas under the curve of 0.719 for amino-terminal pro-brain natriuretic peptide, 0.843 for estimated glomerular filtration rate, 0.656 for high-sensitivity C-reactive peptide, and 0.863 for the 3-marker panel (all P<0.001). Also, the integrated 3-marker panel performed better than the individual markers ( P<0.05). CRS 1 risk correlated with the number of biomarkers showing abnormal levels. Abnormal measurements for at least 2 biomarkers indicated a greater risk of CRS 1 (odds ratio 36.19, 95% confidence interval 8.534-153.455, P<0.001). Conclusions The combination of amino-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate, and high-sensitivity C-reactive peptide at presentation may assist in the prediction of CRS 1 and corresponding risk stratification in patients with acute myocardial infarction.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardio-Renal Syndrome; China; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; Survival Rate

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Topics: Adult; Aged; Biomarkers; Cardio-Renal Syndrome; Diastole; Echocardiography; Female; Humans; Hydronephrosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stents; Transforming Growth Factor beta1; Ventricular Dysfunction; Ventricular Dysfunction, Left

Topics: Cardio-Renal Syndrome; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Cardio-Renal Syndrome; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

To study the protective effects of valsartan (Val) and benazepril, (Ben) combined with atorvastatin (Ato), on cardiorenal syndrome (CRS) in rats.. After establishing cardiorenal syndrome model, the rats were randomly divided into control, Ato, Ben+Ato and Val+Ato groups, which were treated with corresponding drugs. Before and 4 weeks after treatment, the serum creatinine (Scr), blood urea nitrogen (BUN), type-B natriuretic peptide (BNP), aldosterone (ALD), angiotensin (Ang) II, C-reactive protein (CRP), blood lipid and urine protein were determined. The left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) as well as maximum rising and falling rates of left ventricular pressure (±dp/dtmax) were detected. The heart weight index was also determined.. 6, 3, 1 and 2 rats control, Ato, Ben+Ato and Val+Ato groups died, respectively. Compared with control group, the serum Cr, BUN, BNP, ALD, CRP and urinary protein levels in treatment groups significantly decreased, and the blood lipid level, LVDP, LVEDP and heart weight index significantly decreased, with increased LVSP. No statistically significant difference was observed among treatment groups.. Valsartan and benazepril, combined with atorvastatin, can have significant protective effects on cardiorenal functions of rats with CRS, with no significant difference between these two drugs.

Topics: Angiotensin II; Animals; Atorvastatin; Benzazepines; C-Reactive Protein; Cardio-Renal Syndrome; Case-Control Studies; Drug Synergism; Heptanoic Acids; Lipids; Male; Natriuretic Peptide, Brain; Proteinuria; Pyrroles; Random Allocation; Rats; Rats, Sprague-Dawley; Tetrazoles; Valine; Valsartan

The aims to investigate the different protective effects of valsartan and benazepril when combined with atorvastatin in the cardio-renal functions of cardio-renal syndrome (CRS) patients.. A total of 200 early CRS patients were enrolled in the present study, including 104 males and 96 females, with an average age of 62.2 ± 7.7 years. The same group of patients were set as the control group prior to treatment, and then randomly divided into two groups; the A group was treated with valsartan (80 mg/d) and atorvastatin (20 mg/d); the B group was treated with benazepril (10 mg/d) and atorvastatin (20 mg/d). The treatment period was 24 months.. The clinical efficacy and clinical events were observed and the following parameters of each patient were measured before and after treatment: 24h urine protein; creatinine clearance; serum brain natriuretic peptide (BNP); high sensitivity C-reactive protein (hsCRP); blood lipid level; liver function and ejection fraction (EF) value. Compared with the control group, the clinical symptoms of the treatment groups were improved with decreased blood lipid levels, significantly decreased serum BNP and hsCRP levels and significantly increased EF values and creatinine clearance rates (p < 0.01). The differences between the two treatment groups were not statistically significant. The number of patients that stopped treatment due to the development of a cough was significantly higher in the B group than the A group (p < 0.01).. When combined with atorvastatin, both valsartan and benazepril effectively improved the cardio-renal functions of early CRS patients. There was no significant difference between the two treatments however, valsartan appeared to be better tolerated by patients.

Topics: Aged; Antihypertensive Agents; Atorvastatin; Benzazepines; C-Reactive Protein; Cardio-Renal Syndrome; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Protective Agents; Valsartan

The aim of this study was to analyze the dynamic changes in renal function in combination with dynamic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF).. Treatment of ADHF improves cardiac parameters, as reflected by lower levels of NT-proBNP. However this often comes at the cost of worsening renal parameters (e.g., serum creatinine, estimated glomerular filtration rate [eGFR], or serum urea). Both the cardiac and renal markers are validated indicators of prognosis, but it is not yet clear whether the benefits of lowering NT-proBNP are outweighed by the concomitant worsening of renal parameters.. This study was an individual patient data analysis assembled from 6 prospective cohorts consisting of 1,232 patients hospitalized for ADHF. Endpoints were all-cause mortality and the composite of all-cause mortality and/or readmission for a cardiovascular reason within 180 days after discharge.. A significant reduction in NT-proBNP was not associated with worsening of renal function (WRF) or severe WRF (sWRF). A reduction of NT-proBNP of more than 30% during hospitalization determined prognosis (all-cause mortality hazard ratio [HR]: 1.81; 95% confidence Interval [CI]: 1.32 to 2.50; composite endpoint: HR: 1.36, 95% CI: 1.13 to 1.64), regardless of changes in renal function and other clinical variables.. When we defined prognosis, NT-proBNP changes during hospitalization for treatment of ADHF prevailed over parameters for worsening renal function. Severe WRF is a measure of prognosis, but is of lesser value than, and independent of the prognostic changes induced by adequate NT-proBNP reduction. This suggests that in ADHF patients it may be warranted to strive for an optimal decrease in NT-proBNP, even if this induces WRF.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Cardio-Renal Syndrome; Cohort Studies; Confidence Intervals; Databases, Factual; Female; Glomerular Filtration Rate; Heart Failure; Hospital Mortality; Hospitalization; Humans; Kaplan-Meier Estimate; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric

Topics: Cardio-Renal Syndrome; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

Abstract Background: The role of neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic heart failure (HF), however less data are available in patients admitted for acute HF.. We evaluated the role of NGAL in predicting in-hospital worsening renal function (WRF) and post-discharge follow-up during six months period in patients with acute HF. All patients were submitted to creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and B-type natriuretic peptide (BNP) measurement during hospitalization and before discharge.. Patients with chronic kidney dysfunction (CKD) demonstrated higher NGAL respect to subject with preserved renal function (241 ± 218 and 130 ± 80 ng/ml; P = 0.0001). In subgroup that developed WRF during hospitalization, NGAL levels were significantly increased respect to patients without WRF (272 ± 205 versus 136 ± 127 ng/ml; P = 0.0001). A cut off of 134 ng/ml has been related to WRF with good sensibility and specificity (92% and 71% AUC 0.83; P = 0.001). Multivariable Cox regression analysis showed that cut-off of 134 ng/ml was the only marker related to death (HR: 1.75; 95% CI: 1.24-2.45; P < 0.001). Follow-up analysis confirmed that NGAL > 130 ng/ml was associated with adverse events during a six-month period.. Admission NGAL measurement appears a sensible tool for in-hospital WRF prediction as well as an early marker for adverse outcome during post discharge vulnerable phase.

Topics: Acute Disease; Acute-Phase Proteins; Aged; Aged, 80 and over; Biomarkers; Blood Urea Nitrogen; Cardio-Renal Syndrome; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Kidney; Lipocalin-2; Lipocalins; Male; Natriuretic Peptide, Brain; Patient Readmission; Pilot Projects; Prognosis; Prospective Studies; Proto-Oncogene Proteins; Regression Analysis

A pathological connection between the heart and kidney is well recognized as a cardiorenal syndrome, but the underlying mechanism remains undetermined. We hypothesized that this connection is attributable to central haemodynamic alterations.. In 386 patients with hypertension, the radial, carotid and femoral pressure waveforms were recorded with applanation tonometry to estimate the aortic pressure and pulse wave velocity (PWV). The plasma B-type natriuretic peptide (BNP) concentration and urinary albumin/creatinine ratio (UACR), cardiac and renal damage biomarkers, respectively, were also measured for each patient.. The BNP was correlated positively with UACR, aortic pulse pressure and PWV, but inversely with the estimated glomerular filtration rate (eGFR, P < 0.001). The aortic pulse pressure tended to more closely correlate with BNP than the brachial pulse pressure. The presence of (micro)albuminuria (UACR ≥30 mg/g) was associated with BNP elevation (≥50 pg/ml) independently of age, BMI, mean arterial pressure, eGFR and β-blocker treatment (odds ratio: 2.41; P = 0.04). However, further adjustment for the aortic pulse pressure or PWV rendered this albuminuria-BNP relationship insignificant (P = 0.25) and, instead, the aortic pulse pressure emerged as the strongest determinant of BNP elevation (odds ratio: 1.51 per 10mmHg; P = 0.001). Differently from albuminuria, lower eGFR was consistently related to higher plasma BNP, even after controlling for the aortic pressure and PWV.. Concomitant plasma BNP elevation with (micro)albuminuria can be explained by increases in aortic pulse pressure and PWV. This finding suggests that the altered central haemodynamics causes simultaneous damage/dysfunction in the heart and kidney, which could then contribute to cardiorenal syndrome in hypertension.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Aorta; Blood Pressure; Cardio-Renal Syndrome; Creatinine; Glomerular Filtration Rate; Humans; Hypertension; Middle Aged; Natriuretic Peptide, Brain

Topics: Albuminuria; Aorta; Blood Pressure; Cardio-Renal Syndrome; Humans; Hypertension; Natriuretic Peptide, Brain

We analyzed the association between renal and cardiovascular parameters in fetuses with isolated severe urinary tract malformations.. 39 fetuses at a mean gestational age of 23.6 weeks with nephropathies or urinary tract malformations and markedly impaired or absent renal function were prospectively examined. Fetal echocardiography was performed, and thicknesses of the interventricular septum, and left and right ventricular wall were measured. Blood flow velocity waveforms of the umbilical artery, middle cerebral artery, and ductus venosus were obtained by color Doppler ultrasound. Concentrations of circulating n-terminal pro-B-type natriuretic peptide (nt-proBNP), cystatin C, ß2-microglobulin, and hemoglobin were determined from fetal blood samples.. Malformations included 21 cases of obstructive uropathy, 10 fetuses with bilateral nephropathy, and 8 cases of bilateral renal agenesis. Marked biventricular myocardial hypertrophy was present in all cases. The ratio between measured and gestational age-adjusted normal values was 2.01 (interventricular septum), 1.85, and 1.78 (right and left ventricular wall, respectively). Compared to controls, levels of circulating nt-proBNP were significantly increased (median (IQR) 5035 ng/L (5936 ng/L) vs. 1874 ng/L (1092 ng/L); p<0.001). Cystatin C and ß2-microglobulin concentrations were elevated as follows (mean ± SD) 1.85±0.391 mg/L and 8.44±2.423 mg/L, respectively (normal range 1.66±0.202 mg/L and 4.25±0.734 mg/L, respectively). No correlation was detected between cardiovascular parameters and urinary tract morphology and function. Despite increased levels of nt-proBNP cardiovascular function was preserved, with normal fetal Doppler indices in 90.2% of cases.. Urinary tract malformations resulting in severe renal impairment are associated with biventricular myocardial hypertrophy and elevated concentrations of circulating nt-proBNP during fetal life. Cardiovascular findings do not correlate with kidney function or morphology.

Topics: Blood Flow Velocity; Cardio-Renal Syndrome; Echocardiography, Doppler; Fetus; Gestational Age; Heart Ventricles; Hemoglobins; Humans; Infant; Middle Cerebral Artery; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Umbilical Arteries; Urinary Tract; Urologic Diseases

Urine albumin excretion is an important predictor of adverse cardiovascular events in various populations. Its correlation in patients with acute heart failure has not been described.. This prospective, observational study included 115 patients presenting with acute heart failure. The urine albumin/creatinine ratio (UACR) was measured from spot urine samples collected on days 1 and 7 of hospitalization. Median UACR decreased from 83 to 22 mg/gCr on days 1 and 7, respectively (P<0.0001). The proportion of patients with normoalbuminuria (UACR <30 mg/gCr) increased from 31% on day 1 to 60% on day 7, whereas the proportion with microalbuminuria (UACR between 30 and 299 mg/gCr) and macroalbuminuria (UACR ≥300 mg/gCr) decreased, respectively, from 42% and 27% on day 1 to 30% and 10% on day 7 (P<0.0001). These changes in UACR were correlated with changes in serum bilirubin and N-terminal pro b-type natriuretic peptide concentrations (correlation coefficients 1.087 and 0.384, respectively; 95% confidence interval, 0.394-1.781 and 0.087-0.680, respectively; and P=0.003 and 0.013, respectively), although they were not correlated with change in estimated glomerular filtration rate.. In this sample of patients presenting with acute heart failure, urine albumin excretion was often increased at admission to the hospital and decreased significantly within 7 days of treatment. The decrease was correlated with serum N-terminal pro b-type natriuretic peptide and bilirubin concentrations, although neither with baseline nor with changes in indices of renal function.

Topics: Acute Disease; Aged; Aged, 80 and over; Albuminuria; Bilirubin; Biomarkers; Cardio-Renal Syndrome; Comorbidity; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Humans; Japan; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Prospective Studies; Time Factors

Cardio-Renal syndrome may occur as a result of either primarily renal or cardiac dysfunction. This complex interaction requires a tailored approach to manage the underlying pathophysiology while optimizing the patient's symptoms and thus providing the best outcomes. Patients often are admitted to the hospital for signs and symptoms of congestion and fluid overload is the most frequent cause of subsequent re-admission. Fluid management is of paramount importance in the strategy of treatment for heart failure patients. Adequate fluid status should be obtained but a target value should be set according to objective indicators and biomarkers. Once the fluid excess is identified, a careful prescription of fluid removal by diuretics or extracorporeal therapies must be made. While delivering these therapies, adequate monitoring should be performed to prevent unwanted effects such as worsening of renal function or other complications. There is a very narrow window of optimal hydration for heart failure patients. Overhydration can result in myocardial stretching and potential decompensation. Inappropriate dehydration or relative reduction of circulating blood volume may result in distant organ damage caused by inadequate perfusion. We suggest consideration of the "5B" approach. This stands for balance of fluids (reflected by body weight), blood pressure, biomarkers, bioimpedance vector analysis, and blood volume. Addressing these parameters ensures that the most important issues affecting symptoms and outcomes are addressed. Furthermore, the patient is receiving the best possible care while avoiding unwanted side effects of the treatment.

Topics: Acute-Phase Proteins; Biomarkers; Blood Pressure; Blood Volume; Body Composition; Cardio-Renal Syndrome; Electric Impedance; Fluid Therapy; Heart Failure; Humans; Lipocalin-2; Lipocalins; Natriuretic Peptide, Brain; Proto-Oncogene Proteins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which multiple causative factors are involved. The time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the effects of the insult become evident with a loss or decline of renal function. For this reason, pharmaceutical interventions for AKI that have been shown to be renoprotective or beneficial when tested in experimental conditions do not display similar results in the clinical setting. In most cases patients with AHF are admitted with clinical signs and symptoms of congestion and fluid overload. Loop diuretics, typically used to induce an enhanced diuresis in these congested patients, often are associated with a subsequent significant decrease in glomerular filtration rate and cause a creatinine increase that is apparent within 72 hours. Early detection of AKI is not possible with the use of serum creatinine and there is a need for a timely diagnostic tool able to address renal damage while it is happening. We need to define the diagnosis of both AHF and AKI in the early phases of CRS type 1 by coupling a kidney damage marker such as neutrophil gelatinase-associated lipocalin (NGAL) with B-type natriuretic peptide (BNP). Indeed, it would be ideal to make available a panel including whole blood or plasma cardiac and renal biomarkers building specific, pathophysiologically based, molecular profiles. Based on current knowledge and consensus, we can use kidney damage biomarkers such as plasma NGAL for an early diagnosis of AKI. However, differences in individual patient values and uncertainties about the ideal cut-off values may currently limit the application of these biomarkers. We propose that NGAL may increase its usefulness in the diagnosis and prevention of CRS if a curve of plasma values rather than a single plasma measurement is determined. To apply the concept of measuring an NGAL curve in AHF patients, however, assay performance in the lower-range values becomes a critical factor. For this reason, we propose the use of the new extended-range plasma NGAL assay that may contribute to remarkably improve the sensitivity of AKI diagnosis in AHF and lead to more effective intervention strategies.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Biomarkers; Cardio-Renal Syndrome; Early Diagnosis; Humans; Lipocalin-2; Lipocalins; Natriuretic Peptide, Brain; Proto-Oncogene Proteins

Increased filling pressures, or congestion, cause symptoms of heart failure and lead to hospitalizations. A higher rate of hospitalizations determines higher mortality. The most reliable way to decrease admissions is to monitor for signs of congestion, by history and exam, intracardiac pressures or biomarkers, and to modify treatment based on these data. The role of congestion is best understood by comparison of heart failure with preserved and reduced ejection fraction. The morbidity and mortality in both conditions is almost identical. Decreased cardiac output and ventricular remodeling play a major role in patients with decreased ejection fraction but not in those with preserved ejection fraction. The key factor that is present in both conditions and determines their similarity is congestion. Decongestion, or fluid removal, is the most effective treatment for heart failure regardless of ejection fraction. Being the driving force of heart failure, congestion should be the focus of clinical and hemodynamic monitoring and therapy.

Topics: Cardiac Output, Low; Cardio-Renal Syndrome; Diuretics; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Pressure; Ventricular Remodeling

Cardiorenal syndrome is a pathophysiological heart and kidney disorder, in which acute or chronic dysfunction of one organ induces a damage in the other. It's a syndrome more and more often encountered in clinical practice and this implies the need to recognize the syndrome through biochemical markers with a good sensitivity and specificity, since its earliest stages in order to optimize therapy. In addition to widely validated biomarkers, such as BNP, pro BNP, creatinine, GFR and cystatin C, other promising molecules are available, like NGAL (neutrophil gelatinase-associated lipocalin, KIM-1 (kidney injury molecule-1), MCP-1 (monocyte chemotactic peptide), Netrin-1, interleuchin 18 and NAG (N-acetyl-β-glucosa-minidase). The role of these emerging biomarkers is still not completely clarified: hence the need of new clinical trials.

Topics: Acetylglucosaminidase; Biomarkers; Cardio-Renal Syndrome; Chemokine CCL2; Creatinine; Cystatin C; Glomerular Filtration Rate; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-18; Lipocalins; Membrane Glycoproteins; Natriuretic Peptide, Brain; Nerve Growth Factors; Netrin-1; Peptide Fragments; Predictive Value of Tests; Prognosis; Receptors, Virus; Sensitivity and Specificity; Tumor Suppressor Proteins

Patients with chronic heart failure are often characterized by impaired renal function, also referred to as cardiorenal syndrome (CRS). The aim of this study was to assess whether novel markers of kidney injury are elevated in chronic heart failure and CRS.. The new renal biomarkers kidney injury molecule-1 (KIM-1), N-acetyl-ß-d-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) were assessed from urine samples of 173 individuals. Patients with chronic heart failure (n= 150) were characterized by decreased ejection fraction (32 ± 9% vs. controls 62 ± 4%, P < 0.001) and increased plasma N-terminal pro-brain natriuretic peptide (median 1460 pg/mL, interquartile range (IQR) 630-3000 pg/mL vs. controls 56, IQR 25-64l pg/mL, P < 0.001). Urinary analysis showed that KIM-1 was significantly elevated in heart failure patients compared with healthy controls (1100, IQR 620-1920 vs. 550, IQR 320-740 ng/g urinary creatinine, P < 0.001). Further, KIM-1 increased significantly with decreasing left ventricular function (r = -0.37, P < 0.001) and severity of New York Heart Association (NYHA)-class (r = 0.5, P < 0.001). N-acetyl-ß-d-glucosaminidase showed a weaker response but correlated significantly with left ventricular dysfunction (r = -0.18, P= 0.015) and more severe clinical condition (r = 0.22, P= 0.04). In contrast, NGAL showed no significant correlation. Kidney injury molecule-1 and NAG were also predictors of all-cause mortality and the composite of all-cause mortality and rehospitalization for heart failure (all P < 0.05).. Kidney injury molecule-1 and NAG are elevated in symptomatic heart failure. This finding may be present in patients with apparently normal kidney function and indicates tubular injury in chronic heart failure. Kidney injury molecule-1 and NAG are potential markers of CRS with additional prognostic value.

Topics: Acetylglucosaminidase; Adult; Aged; Aged, 80 and over; Biomarkers; Cardio-Renal Syndrome; Chronic Disease; Cohort Studies; Disease-Free Survival; Female; Germany; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Male; Membrane Glycoproteins; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Virus; Severity of Illness Index; Syndrome; Urinalysis

A low serum adiponectin level is associated with a high incidence of coronary artery disease (CAD) in the healthy population. Paradoxically, serum adiponectin is elevated in patients with severe CAD or chronic heart failure. We investigated the determinants of serum high molecular weight (HMW) adiponectin in patients with CAD.. We studied 228 consecutive patients with CAD confirmed by angiography. Anemia was defined as a hemoglobin of <13.0 g/dL in men and<12.0 g/dL in women. A high plasma B-type natriuretic-peptide (BNP) was defined as >100 pg/mL. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min for more than 3 months. The patients with CAD were divided into eight groups according to the presence or absence of anemia, high BNP, and/or CKD.. In all 228 patients with CAD, serum HMW adiponectin correlated positively with age, high-density-lipoprotein cholesterol (HDL-C), and BNP, while this parameter showed negative correlations with body mass index, insulin resistance, triglycerides, eGFR, and hemoglobin. Multivariate analysis showed that HDL-C, BNP, gender, and age were independently associated with the HMW adiponectin. Serum HMW adiponectin was lower in CAD patients with than without metabolic syndrome. Serum HMW adiponectin and the HMW/total adiponectin ratio were highest in CAD patients who had anemia, high BNP, and CKD among the groups.. In patients with CAD, metabolic syndrome is associated with a lower serum HMW adiponectin, while the presence of anemia, high BNP, and CKD is associated with elevation of the serum HMW adiponectin.

Topics: Adiponectin; Aged; Anemia; Biomarkers; Cardio-Renal Syndrome; Coronary Artery Disease; Female; Humans; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Molecular Weight; Natriuretic Peptide, Brain; Syndrome