natriuretic-peptide--brain and Renal-Insufficiency--Chronic

Targeted prevention of heart failure (HF) remains a critical need given the high prevalence of HF morbidity and mortality. Similar to risk-based prevention of atherosclerotic cardiovascular disease, optimal HF prevention strategies should include quantification of risk in the individual patient. In this review, we discuss incorporation of a quantitative risk-based approach into the existing HF staging landscape and the clinical opportunity that exists to translate available data on risk estimation to help guide personalized decision making. We first summarize the recent development of key HF risk prediction tools that can be applied broadly at a population level to estimate risk of incident HF. Next, we provide an in-depth description of the clinical utility of biomarkers to personalize risk estimation in select patients at the highest risk of developing HF. We also discuss integration of genomics-enhanced approaches (eg,

Topics: Antineoplastic Agents; Autoimmune Diseases; Biomarkers; Cardiac Imaging Techniques; Cardiotoxicity; Carrier Proteins; Comorbidity; Connectin; Female; Genomics; Heart Failure; HIV Infections; Humans; Liver Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Prealbumin; Precision Medicine; Pregnancy; Premature Birth; Radiotherapy; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Troponin T

Heart failure remains a continuing threat to patients with chronic kidney disease (CKD). Although various heart failure biomarkers have been applied for early detection, diagnosis and prognosis in CKD, these are easily affected by renal insufficiency thus limiting use in these patients. In this review, the major four groups of heart failure biomarkers are explored. These include those associated with: myocardial stretch, ie, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP); myocyte injury, ie, high-sensitivity troponin T (hsTnT), heart-type fatty acid-binding protein (H-FABP); fibrosis, matrix remodelling and inflammation, ie, soluble growth stimulating gene 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15); and renal function, ie, neutrophil gelatinase-associated lipocalin (NGAL) kidney injury molecule-1 (KIM-1), cystatin C (CysC), urinary sodium and urinary albumin. This review highlights classic heart failure biomarkers with critical values adjusted to glomerular filtration rate, summarizes research progress of new heart failure biomarkers and future research directions. Because diagnostic and prognostic usefulness of a single time point biomarker is limited, biomarkers should be combined and monitored at multiple times for optimal clinical impact.

Topics: Biomarkers; Glomerular Filtration Rate; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic

Cardiovascular disease is an important complication for patients with chronic kidney disease (CKD), warranting accurate risk prediction, but clinical guidelines are inconsistent regarding whether or how to use information on measures of CKD for predicting risk. Recent large meta-analyses have shown that key CKD measures (estimated glomerular filtration rate and albuminuria) improve cardiovascular risk prediction beyond traditional risk factors, especially when albuminuria is added to prediction models. In addition, several recent studies have shown that the use of filtration markers other than serum creatinine, cystatin C, and β

Topics: Albuminuria; beta 2-Microglobulin; Calcium; Cardiovascular Diseases; Coronary Vessels; Creatinine; Cystatin C; Glomerular Filtration Rate; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Assessment; Troponin

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function.

Topics: Atrial Natriuretic Factor; Diuretics; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Glomerulus; Kidney Tubules; Natriuretic Peptide, Brain; Renal Circulation; Renal Insufficiency, Chronic; Sodium; Water-Electrolyte Imbalance

This study sought to review the literature for risk prediction models in patients with heart failure and to identify the most consistently reported independent predictors of risk across models.. Risk assessment provides information about patient prognosis, guides decision making about the type and intensity of care, and enables better understanding of provider performance.. MEDLINE and EMBASE were searched from January 1995 to March 2013, followed by hand searches of the retrieved reference lists. Studies were eligible if they reported at least 1 multivariable model for risk prediction of death, hospitalization, or both in patients with heart failure and reported model performance. We ranked reported individual risk predictors by their strength of association with the outcome and assessed the association of model performance with study characteristics.. Sixty-four main models and 50 modifications from 48 studies met the inclusion criteria. Of the 64 main models, 43 models predicted death, 10 hospitalization, and 11 death or hospitalization. The discriminatory ability of the models for prediction of death appeared to be higher than that for prediction of death or hospitalization or prediction of hospitalization alone (p = 0.0003). A wide variation between studies in clinical settings, population characteristics, sample size, and variables used for model development was observed, but these features were not significantly associated with the discriminatory performance of the models. A few strong predictors emerged for prediction of death; the most consistently reported predictors were age, renal function, blood pressure, blood sodium level, left ventricular ejection fraction, sex, brain natriuretic peptide level, New York Heart Association functional class, diabetes, weight or body mass index, and exercise capacity.. There are several clinically useful and well-validated death prediction models in patients with heart failure. Although the studies differed in many respects, the models largely included a few common markers of risk.

Topics: Age Factors; Blood Pressure; Body Mass Index; Comorbidity; Decision Support Techniques; Diabetes Mellitus; Exercise Tolerance; Female; Heart Failure; Hospitalization; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Severity of Illness Index; Sex Factors; Sodium

Left ventricular failure (LVF) is a clinical syndrome caused by abnormal systolic or diastolic function failing to meet the metabolic requirements of the body. It is important to diagnose and manage LVF in the earliest stages to prevent mortality and morbidity. This article extensively reviews the diagnostic, therapeutic, and prognostic utility of natriuretic peptides in LVF.

Topics: Biomarkers; Half-Life; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis; Pulmonary Embolism; Renal Insufficiency, Chronic; Stroke; Ventricular Dysfunction, Left

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

Concomitant cardiac and renal dysfunction has been termed the cardiorenal syndrome (CRS). This clinical condition usually manifests as heart failure with worsening renal function and occurs frequently in the acute care setting. A consistent definition of CRS has not been universally agreed upon, although a recent classification of CRS describes several subtypes depending on the primary organ injured and the chronicity of the injury. CRS may develop in adults and children and is a strong predictor of morbidity and mortality in hospitalized and ambulatory patients. The underlying physiology of CRS is not well understood, creating a significant challenge for clinicians when treating heart failure patients with renal insufficiency. This review summarizes recent data characterizing the incidence, physiology, and management of children who have heart failure and acute kidney injury.

Topics: Acute Kidney Injury; Child; Creatinine; Heart Failure; Humans; Kidney; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency; Renal Insufficiency, Chronic; Syndrome

Congestive heart failure (CHF) is an increasingly common medical condition and the fastest growing cardiovascular diagnosis in North America. Over one-third of patients with heart failure also have renal insufficiency. It has been shown that renal insufficiency confers worsened outcomes to patients with heart failure. However, a majority of the larger and therapy-defining heart failure medication and device trials exclude patients with advanced renal dysfunction. These studies also infrequently perform subgroup analyses based on the degree of renal dysfunction. The lack of information on heart failure patients who have renal insufficiency likely contributes to their being prescribed mortality and morbidity reducing medications and receiving diagnostic and therapeutic procedures at lower rates than heart failure patients with normal renal function. Inclusion of patients with renal insufficiency in heart failure studies and published guidelines for medication, device, and interventional therapies would likely improve patient outcomes.

Topics: Acute Disease; Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiac Catheterization; Cardiac Pacing, Artificial; Clinical Trials as Topic; Digoxin; Heart Failure; Humans; Milrinone; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Treatment Outcome; Ultrafiltration

Topics: Acute Disease; Adult; Age Distribution; Aged; Albuminuria; Anemia; Calcium Metabolism Disorders; Comorbidity; Coronary Disease; Diabetes Complications; Female; Humans; Hyperhomocysteinemia; Hyperlipidemias; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Phosphorus Metabolism Disorders; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Sex Distribution; Urotensins

Achievement of decongestion in acute heart failure (AHF) is associated with improved survival and cardiovascular outcomes but can be associated with acute declines in estimated glomerular filtration rate (eGFR). We examined whether the rate of in-hospital decongestion is associated with longer term kidney function decline.. Post hoc analysis of trial data.. Patients with ≥2 measures of kidney function (n = 3,500) from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial.. In-hospital rate of change in assessments of volume overload, including B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and clinical congestion score (0-12); and rate of change in hemoconcentration including measures of hematocrit, albumin, and total protein.. Incident chronic kidney disease GFR category 4 or worse (chronic kidney disease [CKD] categories G4-G5; defined by a new eGFR of <30 mL/min/1.73 m. Multivariable cause-specific hazards models.. Over median 10-month follow-up period, faster decreases in volume overload and more rapid increases in hemoconcentration were associated with a decreased risk of incident CKD G4-G5 and eGFR decline of >40%. In adjusted analyses, for every 6% faster decline in BNP per week, there was a 32% lower risk of both incident CKD G4-G5 (HR, 0.68 [95% CI, 0.58-0.79]) and eGFR decline of >40% (HR, 0.68 [95% CI, 0.57-0.80]). For every 1% faster increase per week in absolute hematocrit, there was a lower risk for both incident CKD G4-G5 (HR, 0.73 [95% CI, 0.64-0.84]) and eGFR decline of >40% (HR, 0.82 [95% CI, 0.71-0.95]), with results consistent for other biomarkers.. Possibility of residual confounding.. These results provide reassurance that more rapid decongestion in patients with AHF does not increase the risk of adverse kidney outcomes in patients with heart failure.

Topics: Biomarkers; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Risk Factors; Water-Electrolyte Imbalance

The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization.. The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk.. Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations.. Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78).. In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532).

Topics: Atrasentan; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Endothelin Receptor Antagonists; Endothelins; Heart Failure; Humans; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Weight Gain

Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.. We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed.. A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m. Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).

Topics: Aged; Albuminuria; Blood Pressure; Chlorthalidone; Creatinine; Diuretics; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Severity of Illness Index; Sodium Chloride Symporter Inhibitors

Patients with CKD have an impaired health-related quality of life (QoL). Most studies have been conducted on dialysis patients, and less is known about QoL and its determinants in predialysis patients. We studied the association between QoL and comorbidities, cardiac biomarkers, echocardiography, and mortality in patients with CKD stage 4-5 not on dialysis.. A total of 140 patients enrolled in the Chronic Arterial Disease, Quality of Life and Mortality in Chronic Kidney Injury (CADKID) study filled the Kidney Disease Quality of Life Short Form (KDQOL-SF) at the beginning of the study. Echocardiography and biochemical parameters were obtained at baseline. Patients were followed up for at least 2 years or until death.. The median age was 66 years, and 51 (36%) patients were female. The median estimated glomerular filtration rate was 13 mL/min per 1.73 m2. Obesity, diabetes, atrial fibrillation, and congestive heart failure were associated with lower QoL scores in multiple KDQOL-SF domains. Cardiac biomarkers, troponin T (p = 0.02), N-terminal pro-B-type natriuretic peptide (p = 0.006), and the echocardiographic parameter of cardiac systolic function left ventricular global longitudinal strain (p = 0.02) were significant predictors of lower physical component summary (PCS) score in multivariable regression models after controlling for age, BMI, and diabetes. A low PCS score predicted mortality in a multivariable Cox proportional hazards model [HR 0.96 (95% CI 0.92-0.99), p = 0.03]. QoL was not associated with kidney disease progression.. Impaired QoL in CKD stage 4-5 patients not on dialysis is associated with cardiac biomarker levels, echocardiographic indices, and mortality.

Topics: Aged; Echocardiography; Female; Follow-Up Studies; Glomerular Filtration Rate; Health Status; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic; Troponin T

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure.. The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care.. The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

Topics: Acute Disease; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Disease Progression; Glucosides; Heart Failure; Hospital Mortality; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Hypotension; Hypovolemia; Insulin; Natriuresis; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; Weight Loss

Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients.. The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo. Serum and plasma were collected before the run-in, then 6 and 12 months post-randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT-ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and galectin-3. Left ventricular global longitudinal strain (GLS) was measured by echocardiography at baseline.. Seventy-two participants were recruited of whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS (Spearman's rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median change scores from baseline to 12 months did not differ significantly between participants with complete biomarker data randomized to carvedilol (n=15) or placebo (n=16) for any biomarkers.. NT-proBNP and hs-TnT were associated with GLS. However, changes in levels of the biomarkers from baseline to 12 months were not different between groups randomized to carvedilol and placebo.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Biomarkers; Carbazoles; Carvedilol; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Renal Insufficiency, Chronic; Troponin T

Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD).. B-type natriuretic peptide and NT-proBNP were measured using commercially available clinical-grade immune-assays at baseline and at the end of a 4-day treatment with placebo and linagliptin. Changes from baseline during each treatment arm, as well as placebo-subtracted effects of linagliptin on BNP and NT-proBNP were calculated.. 46 patients completed the study, 18 of whom were affected by CKD. Baseline BNP and NT-proBNP levels increased with age, were elevated in CKD patients, and inversely correlated with estimated glomerular filtration rate. No significant change was detected in BNP and NT-proBNP levels after treatment with linagliptin or placebo in patients with or without CKD. Only in CKD patients the placebo-subtracted effect of linagliptin indicated a significant reduction in NT-proBNP levels, but this finding was not statistically robust.. Acute treatment with a DPP-4i exerts no clinically-meaningful effects on BNP and NT-proBNP. As routinely used immunoassays do not discriminate between intact/active and cleaved BNP, these data cannot rule out an effect of DPP-4i on HF pathophysiology. Trial registration NCT01617824.

Topics: Aged; Biomarkers; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Female; Glomerular Filtration Rate; Humans; Immunoassay; Kidney; Linagliptin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Single-Blind Method; Time Factors; Treatment Outcome

Improved prediction of early post-discharge death or rehospitalization after admission for acute heart failure is a major unmet need. We evaluated the value of biomarkers to predict either low or high risk for early post-discharge events.. A total of 1653 patients enrolled in the PROTECT trial who were discharged alive and with available blood samples were included. Forty-seven biomarkers were serially evaluated in these patients. Measurement closest to discharge was used to evaluate the predictive value of biomarkers for low and high post-discharge risk. Patients were classified as 'low risk' if post-discharge 30-day risk of death or heart failure rehospitalization was <5% while risk >20% was used to define 'high risk'. Cut-off values that yielded a 95% negative predictive value and a 20% positive predictive value were identified for each biomarker. Partial area under the receiver operating characteristic curve (pAUC) in the high-sensitivity and high-specificity regions was calculated to compare low-risk and high-risk predictive values. Of patients analysed, 193 (11.7%) patients reached the 30-day death or heart failure rehospitalization outcome. We found marked differences between low-risk and high-risk predictors. Cardiac-specific troponin I was the strongest biomarker for low-risk prediction (pAUC = 0.552, 95% confidence interval 0.52-0.58) while endothelin-1 showed better performance for high-risk prediction (pAUC = 0.560, 95% confidence interval 0.53-0.59). Several biomarkers (individually and in combination) provided added predictive value, on top of a clinical model, in both low-risk and high-risk regions.. Different biomarkers predicted low risk vs. high risk of early post-discharge death or heart failure readmission in patients hospitalized for acute heart failure.

Topics: Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Patient Discharge; Patient Readmission; Peptide Fragments; Prognosis; Purinergic P1 Receptor Antagonists; Renal Insufficiency, Chronic; Risk Assessment; ROC Curve; Survival Rate

The role of brain natriuretic peptide (BNP) in the prevention of contrast-induced nephropathy (CIN) is unknown. This study aimed to investigate BNP's effect on CIN in chronic kidney disease (CKD) patients undergoing elective percutaneous coronary intervention (PCI) or coronary angiography (CAG). The patients were randomized to BNP (0.005 μg/kg/min before contrast media (CM) exposure and saline hydration, n = 106) or saline hydration alone (n = 103). Cystatin C, serum creatinine (SCr) levels, and estimated glomerular filtration rates (eGFR) were assessed at several time points. The primary endpoint was CIN incidence; secondary endpoint included changes in cystatin C, SCr, and eGFR. CIN incidence was significantly lower in the BNP group compared to controls (6.6% versus 16.5%, P = 0.025). In addition, a more significant deterioration of eGFR, cystatin C, and SCr from 48 h to 1 week (P < 0.05) was observed in controls compared to the BNP group. Although eGFR gradually deteriorated in both groups, a faster recovery was achieved in the BNP group. Multivariate logistic regression revealed that using >100 mL of CM (odds ratio: 4.36, P = 0.004) and BNP administration (odds ratio: 0.21, P = 0.006) were independently associated with CIN. Combined with hydration, exogenous BNP administration before CM effectively decreases CIN incidence in CKD patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Contrast Media; Coronary Angiography; Creatinine; Female; Glomerulonephritis; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Recombinant Proteins; Renal Insufficiency, Chronic; Risk Factors

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, was evaluated in Japanese patients with heart failure (HF) with reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.. ARTS-HF Japan was a randomized, double-blind, phase 2b study. Patients (n=72) received oral, once-daily (o.d.) finerenone (2.5, 5, 7.5, 10 or 15 mg, up-titrated to 5, 10, 15, 20, or 20 mg, respectively, on day 30) or eplerenone (25 mg every other day, increased to 25 mg o.d. on day 30, and 50 mg on day 60) for 90 days. The primary endpoint was the proportion of individuals with a decrease of >30% in plasma NT-proBNP at day 90. Safety endpoints included the incidence of hyperkalemia. Decreases in NT-proBNP occurred in 23.1% of patients in the eplerenone group and 15.4%, 23.1%, 45.5%, 27.3% and 45.5% in the 2.5→5 mg, 5→10 mg, 7.5→15 mg, 10→20 mg and 15→20 mg finerenone groups, respectively (all P=NS). Mean changes in serum potassium levels were similar between groups.. Because of the small sample size, limited conclusions can be drawn. Considering the results of ARTS-HF and that finerenone was well tolerated in Japanese patients in ARTS-HF Japan, the safety and efficacy of finerenone should be further explored in a large outcomes trial including Japanese patients. (Circ J 2016; 80: 1113-1122).

Topics: Adult; Chronic Disease; Diabetes Mellitus; Double-Blind Method; Eplerenone; Heart Failure; Humans; Hyperkalemia; Japan; Naphthyridines; Natriuretic Peptide, Brain; Patient Safety; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus.. Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively, on Day 30) or eplerenone (25 mg every other day, increased to 25 mg once daily on Day 30, and to 50 mg once daily on Day 60) for 90 days. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to Day 90. A key exploratory endpoint was a composite clinical endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentation for worsening HF until Day 90. Mean age ranged from 69.2 to 72.5 years in different treatment groups (standard deviation 9.7-10.6 years). Decreases in NT-proBNP of >30% from baseline occurred in 37.2% of patients in the eplerenone group and 30.9, 32.5, 37.3, 38.8, and 34.2% in the 2.5→5, 5→10, 7.5→15, 10→20, and 15→20 mg finerenone groups, respectively (P = 0.42-0.88). Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred numerically less frequently in finerenone-treated patients compared with eplerenone; this difference reached nominal statistical significance in the 10→20 mg group (hazard ratio 0.56, 95% confidence interval, CI, 0.35; 0.90; nominal P = 0.02), despite the fact that this phase 2 study was not designed to detect statistical significant differences. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients, with a balanced distribution among all treatment groups.. Finerenone was well tolerated and induced a 30% or greater decrease in NT-proBNP levels in a similar proportion of patients to eplerenone. The finding of reduced clinical events in the finerenone 10→20 mg group should be further explored in a large outcomes trial.

Topics: Aged; Chronic Disease; Diabetes Mellitus; Double-Blind Method; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction.. The MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF; NCT01807221) is a multicentre, randomized, double-blind, active-comparator-controlled, six-parallel-group, phase 2b dose-finding study. In total, 1060 patients with HFrEF and concomitant type 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5-20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days). The primary objective is to investigate the safety and potential efficacy (measured as the percentage of individuals with a decrease in plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP] of more than 30% relative to baseline at day 90 ± 2) of different oral doses of finerenone compared with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health-related quality of life from baseline.. ARTS-HF is the first phase 2b clinical trial to investigate the effects of finerenone on plasma NT-proBNP in a high-risk population of patients who have worsening chronic HF with type 2 diabetes mellitus and/or CKD presenting at the emergency department.

Topics: Comorbidity; Diabetes Mellitus, Type 2; Double-Blind Method; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Naphthyridines; Natriuretic Agents; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Spironolactone

Brain natriuretic peptide (BNP), N-terminal-proBNP (NT-proBNP), and high sensitive cardiac troponin T (TnT) are markers that are elevated in chronic kidney disease and correlate with increased risk of mortality. Data are conflicting on the effect of biomarker levels by hemodialysis (HD).Our aim was to clarify to what extent HD with low-flux (LF) versus high-flux (HF) membranes affects the plasma levels of BNP, NT-proBNP, and TnT.. 31 HD patients were included in a crossover design, randomized to start dialysis with a LF-HD or HF-HD dialyzer. Each patient was his/her own control. The dialyses included in the study were the first treatments of two consecutive weeks with each mode of dialysis. Patients normally on hemodiafiltration (HDF) also performed a HDF the third week. Values after HD were corrected for extent of ultrafiltration.. During LF-HD the biomarkers NT-proBNP and TnT increased (15 versus 6%, P ≤ .001) while there was a slight decrease in BNP (P<.05). During HF-HD the NT-proBNP, BNP and TnT levels decreased (P ≤ .01 for all). During HDF all three markers decreased (P<.01 for all). The rise in TnT during LF-HD correlated with dialysis vintage (months on HD, r = .407, P = .026), Kt/V-urea (r = .383, P = .037), HD time in hours/treatment (r = .447, P = .013) and inversely with residual urinary output (r = -.495, P = .005). The baseline levels of BNP and NT-proBNP correlated with blood pressure.. Cardiac biomarkers increase slightly during LF-HD. A HF-HD eliminates the biomarkers and can mask increases caused by, e.g., myocardial infarction.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cross-Over Studies; Equipment Design; Female; Heart Diseases; Humans; Male; Membranes, Artificial; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic; Sweden; Time Factors; Treatment Outcome; Troponin T

Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol.. In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide.. During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged.. During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.

Topics: Aged; Arginine Vasopressin; Atorvastatin; Atrial Natriuretic Factor; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Rate; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Tubules; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; omega-N-Methylarginine; Pulse Wave Analysis; Pyrroles; Renal Insufficiency, Chronic; Treatment Outcome; Vascular Stiffness; Vasopressins

Patients on chronic dialysis are at increased risk of vitamin D deficiency. In observational studies plasma 25-hydroxyvitamin D (p-25(OH) D) levels are inversely correlated with plasma BNP and adverse cardiovascular outcomes. Whether a causal relation exists has yet to be established. The aim of this study was to test the hypothesis that cholecalciferol supplementation improves cardiac function and reduces blood pressure (BP) and pulse wave velocity (PWV) in patients on chronic dialysis.. In a randomized, placebo-controlled, double-blind study, we investigated the effect of 75 μg (3000 IU) cholecalciferol daily for 6 months, in patients on chronic dialysis. We performed two-dimensional echocardiography, with doppler and tissue-doppler imaging, 24-h ambulatory BP (24-h BP), PWV, augmentation index (AIx), central BP (cBP) and brain natriuretic peptide (BNP) measurements at baseline and after 6 months.. Sixty-four patients were allocated to the study. Fifty dialysis patients with a mean age of 68 years (range: 46-88) and baseline p-25(OH) D of 28 (20;53) nmol/l completed the trial. Cholecalciferol increased left ventricular (LV) volume, but had no impact on other parameters regarding LV structure or left atrial structure. LV systolic function, LV diastolic function, PWV, cBP, AIx and BNP were not changed in placebo or cholecalciferol group at follow-up. 24-h BP decreased significantly in placebo group and tended to decrease in cholecalciferol group without any difference between treatments.. Six months of cholecalciferol treatment in patients on chronic dialysis did not improve 24-h BP, arterial stiffness or cardiac function.. NCT01312714, Registration Date: March 9, 2011.

Topics: Aged; Blood Pressure; Cholecalciferol; Double-Blind Method; Female; Heart; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Placebo Effect; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin K Deficiency; Vitamins

Dietary sodium restriction is a key management strategy in chronic kidney disease (CKD). Recent evidence has demonstrated short-term reduction in blood pressure (BP) and proteinuria with sodium restriction, however the effect on other cardiovascular-related risk factors requires investigation in CKD.. The LowSALT CKD study involved 20 hypertensive Stage III-IV CKD patients counselled by a dietitian to consume a low-sodium diet (<100 mmol/day). The study was a randomised crossover trial comparing 2 weeks of high-sodium (additional 120 mmol sodium tablets) and low-sodium intake (placebo). Measurements were taken after each crossover arm including BP (peripheral and central), adipokines (inflammation markers and adiponectin), volume markers (extracellular-to-intracellular [E/I] fluid ratio; N-terminal pro-brain natriuretic peptide [NT-proBNP]), kidney function (estimated Glomerular Filtration Rate [eGFR]) and proteinuria (urine protein-creatinine ratio [PCR] and albumin-creatinine ratio [ACR]). Outcomes were compared using paired t-test for each cross-over arm.. BP-lowering benefits of a low-sodium intake (peripheral BP (mean ± SD) 148/82 ± 21/12 mmHg) from high-sodium (159/87 ± 15/10 mmHg) intake were reflected in central BP and a reduction in eGFR, PCR, ACR, NTproBNP and E/I ratio. There was no change in inflammatory markers, total or high molecular weight adiponectin.. Short-term benefits of sodium restriction on BP were reflected in significant change in kidney function and fluid volume parameters. Larger, long-term adequately powered trials in CKD are necessary to confirm these results.. Universal Trial Number U1111-1125-2149 registered on 13/10/2011; Australian New Zealand Clinical Trials Registry Number ACTRN12611001097932 registered on 21/10/2011.

Topics: Adipokines; Aged; Body Fluids; Creatinine; Diet, Sodium-Restricted; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome

A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.. We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.. Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.

Topics: Aged; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oleanolic Acid; Patient Safety; Predictive Value of Tests; Reference Values; Renal Insufficiency, Chronic; Risk Factors; Severity of Illness Index; Survival Rate; Treatment Outcome

Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146).. One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73 m(2)), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (-2.79 mL/m(2), 95% CI -4.00 to -1.59 mL/m(2)) in the paricalcitol group compared with the placebo group (-0.70 mL/m(2) [95% CI -1.93 to 0.53 mL/m(2)], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03).. Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.

Topics: Administration, Oral; Aged; Bone Density Conservation Agents; Cardiac Volume; Double-Blind Method; Echocardiography; Ergocalciferols; Female; Heart Atria; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic

This study assessed plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) as a prognostic marker of cardiovascular risk in patients with chronic kidney disease stages 3-4 and anaemia treated with epoetin beta to two haemoglobin target ranges.. Of 603 patients enrolled in the Cardiovascular Risk Reduction by Early Anaemia Treatment with Epoetin Beta (CREATE) trial (baseline creatinine clearance 15-35 mL/min; haemoglobin 11.0-12.5 g/dL), 291 were included in this sub-study. Patients received subcutaneous epoetin beta either immediately after randomisation (target 13.0-15.0 g/dL; Group 1), or after their haemoglobin levels had fallen < 10.5 g/dL (target 10.5-11.5 g/dL; Group 2). Chronic heart failure New York Heart Association class III-IV was an exclusion criterion. (ClinicalTrials.gov Identifier: NCT00321919). Cardiovascular event rates were higher in patients with baseline NT-proBNP > 400 vs. ≤ 400 pg/mL (39 vs. 13 events; p = 0.0002). Dialysis was initiated in 68 vs. 42 patients with NT-proBNP > 400 vs. ≤ 400 pg/mL (p = 0.0003). Amongst patients with NT-proBNP > 400 pg/mL, there was no significant difference between treatment groups in risk of cardiovascular events (HR = 0.57; p = 0.08) or time to dialysis (HR = 0.65; p = 0.08). The overall interpretation of this substudy is, however, limited by its relatively small sample size which, together with low clinical event rates, result in a lack of statistical power for some analyses and should be viewed as being hypothesis-generating in nature.. In chronic kidney disease patients with mild-to-moderate anaemia, elevated baseline plasma NT-proBNP levels are associated with a higher risk of cardiovascular events and an accelerated progression towards end-stage renal disease.

Topics: Aged; Anemia; Biomarkers; Cardiovascular Diseases; Comorbidity; Erythropoietin; Female; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Recombinant Proteins; Renal Insufficiency, Chronic; Risk Assessment

Strategies to preserve renal function and enhance diuretic responsiveness during therapy for heart failure (HF) are needed. We hypothesized that brain natriuretic peptide (nesiritide) added to standard HF therapy would preserve renal function and enhance diuretic responsiveness.. Patients with HF with underlying renal dysfunction who were admitted with volume overload were randomized to standard therapy with nesiritide (2 mug/kg bolus; 0.01 mug/kg/min for 48 hours) or without nesiritide. Patients requiring intravenous vasodilator or inotropic therapy for rapid symptom relief were ineligible. In all patients, diuretics were administered according to a standardized dosing algorithm.. Patients (n = 72) had a mean creatinine level of 1.75 +/- 0.59 mg/dL. Patients receiving nesiritide had a lesser increase in creatinine (P = .048) and blood urea nitrogen (P = .02), but a greater reduction in blood pressure (P < .01). Nesiritide did not enhance diuretic responsiveness (P = .57) but increased 3'5' cyclic guanosine monophosphate and decreased endothelin more (P < .05 for both). There were no differences in the change in atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide, plasma renin activity, angiotensin II, and aldosterone between groups.. When used as adjuvant "renal protective" therapy in patients with HF with renal dysfunction, the recommended dose of nesiritide reduced blood pressure, did not seem to worsen renal function, and suppressed endothelin but did not enhance diuretic responsiveness or prevent activation of the renin-angiotensin-aldosterone system.

Topics: Aged; Algorithms; Blood Urea Nitrogen; Creatinine; Cyclic GMP; Diuresis; Drug Administration Schedule; Drug Therapy, Combination; Endothelium; Female; Heart Failure; Humans; Kidney; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Spironolactone; Stroke Volume; Time Factors

Our objective was to evaluate in a double-blind, randomized, placebo-controlled study possible modifications in NT-pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels together with clinical and functional parameters, in a group of anemic patients with chronic heart failure (CHF) and chronic renal failure (CRF) receiving intravenous iron therapy, without recombinant human erythropoietin (rhEPO), versus placebo.. Chronic heart failure and CRF associated with absolute or relative iron deficiency anemia is a common problem. This situation is linked with a variable inflammatory status. Both NT-proBNP and CRP are recognized markers for left ventricular dysfunction and inflammatory status, respectively. In this double-blind, randomized, placebo-controlled study, modifications in NT-proBNP and CRP level and clinical and functional parameters, in anemic patients with CHF and CRF receiving intravenous iron therapy, without rhEPO, versus placebo were evaluated.. Forty patients with hemoglobin (Hb) <12.5 g/dl, transferrin saturation <20%, ferritin <100 ng/ml, creatinine clearance (CrCl) <90 ml/min, and left ventricular ejection fraction (LVEF) < or =35% were randomized into 2 groups (n = 20 for each). For 5 weeks, group A received isotonic saline solution and group B received iron sucrose complex, 200 mg weekly. Minnesota Living with Heart Failure Questionnaire (MLHFQ) and 6-min walk (6MW) test were performed. NT-pro brain natriuretic peptide and CRP were evaluated throughout the study. No patients received erythroprotein any time.. After 6 months follow-up, group B showed better hematology values and CrCl (p < 0.01) and lower NT-proBNP (117.5 +/- 87.4 pg/ml vs. 450.9 +/- 248.8 pg/ml, p < 0.01) and CRP (2.3 +/- 0.8 mg/l vs. 6.5 +/- 3.7 mg/l, p < 0.01). There was a correlation initially (p < 0.01) between Hb and NT-proBNP (group A: r = -0.94 and group B: r = -0.81) and after 6 months only in group A: r = -0.80. Similar correlations were observed with Hb and CRP. Left ventricular ejection fraction percentage (35.7 +/- 4.7 vs. 28.8 +/- 2.4), MLHFQ score, and 6MW test were all improved in group B (p < 0.01). Additionally, group B had fewer hospitalizations: 0 of 20 versus group A, 5 of 20 (p < 0.01; relative risk = 2.33).. Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF. This situation was associated with an improvement in LVEF, NYHA functional class, exercise capacity, renal function, and better quality of life.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Double-Blind Method; Exercise Tolerance; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Heart Failure; Hematinics; Hospitalization; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prospective Studies; Quality of Life; Renal Insufficiency, Chronic; Treatment Outcome

Chronic kidney disease (CKD) is common in heart failure (HF). Chronic kidney disease often worsens the prognosis and impairs the management of patients with HF. Chronic kidney disease is frequently accompanied by sarcopenia, which limits the benefits of cardiac rehabilitation (CR). The aim of this study was to evaluate the impact of CR on cardiorespiratory fitness in HF patients with reduced ejection fraction (HFrEF) according to the CKD stage.. We conducted a retrospective study including 567 consecutive patients with HFrEF, who underwent a 4-wk CR program, and who were evaluated by cardiorespiratory exercise test before and after the program. Patients were stratified according to their estimated glomerular filtration rate (eGFR). We performed multivariate analysis looking for factors associated with an improvement of 10% in peak oxygen uptake (V˙ o2peak ).. Thirty-eight percent of patients had eGFR <60 mL/min/1.73m². With decreasing eGFR, we observed deterioration in V˙ o2peak , first ventilatory threshold (VT1) and workload and an increase in brain natriuretic peptide levels at baseline. After CR, there was an improvement in V˙ O2peak (15.3 vs 17.8 mL/kg/min, P < .001), VT1 (10.5 vs 12.4 mL/kg/min, P < .001), workload (77 vs 94 W, P < .001), and brain natriuretic peptide (688 vs 488 pg/mL, P < .001). These improvements were statistically significant for all stages of CKD. In a multivariate analysis predicting factors associated with V˙ o2peak improvement, renal function did not interfere with results.. Cardiac rehabilitation is beneficial in patients with HFrEF with CKD regardless of CKD stage. The presence of CKD should not prevent the prescription of CR in patients with HFrEF.

Topics: Cardiac Rehabilitation; Heart Failure; Humans; Kidney; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Retrospective Studies; Stroke Volume

International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice.. To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM).. A prospective screening study at the DM complication screening centre was performed.. Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%.. NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Topics: Aged; Atrial Fibrillation; Biomarkers; Diabetes Mellitus, Type 2; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Stroke; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Cardiovascular mortality is a leading cause of death in chronic kidney disease (CKD), as is IgA nephropathy (IgAN). The purpose of this study is to find different biomarkers to estimate the outcome of the disease, which is significantly influenced by the changes in vessels (characterized by arterial stiffness) and the heart. In our cross-sectional study, 90 patients with IgAN were examined. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was measured as a heart failure biomarker by an automated immonoassay method, while the carboxy-terminal telopeptide of collagen type I (CITP) as a fibrosis marker was determined using ELISA kits. Arterial stiffness was determined by measuring carotid-femoral pulse wave velocity (cfPWV). Renal function and routine echocardiography examinations were performed as well. Based on eGFR, patients were separated into two categories, CKD 1-2 and CKD 3-5. There were significantly higher NT-proBNP (

Topics: Biomarkers; Cross-Sectional Studies; Glomerulonephritis, IGA; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pulse Wave Analysis; Renal Insufficiency, Chronic; Vascular Stiffness

Topics: Biomarkers; Child; Disease Progression; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

Patients with chronic renal insufficiency often show symptoms that are atypical for cardiovascular problems. The correct interpretation of the symptoms is crucial in order to correctly assess the risk of a heart-related emergency and to take preventive measures and initiate the right therapy. Biomarkers such as NT-proBNP, troponin T or hsCRP (highly sensitive CRP) are independent predictors of mortality, but do not replace instrument-based diagnostics. Patients with renal insufficiency often have stiff vessels which, due to the premature reflection of the pulse wave, can lead to left ventricular dysfunction and ultimately to heart failure.

Topics: Biomarkers; Cardiovascular Diseases; Heart Disease Risk Factors; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic; Risk Factors; Troponin T

BACKGROUND N-terminal proatrial natriuretic peptide (NT-proBNP) levels are often markedly elevated in patients with chronic kidney disease (CKD). Identifying novel biomarkers is an important step toward effective diagnosis. Interleukin-1 receptor-like 1 (IL1RL1) protein and human/Soluble suppression of tumorigenesis-2 (sST2) are promising biomarkers for heart failure (HF). This study aimed to assess the trend of NT-proBNP and sST2 in chronic kidney disease and their diagnostic value for HF. MATERIAL AND METHODS This study was carried out on 420 patients who were divided into a no heart failure group (N=182) and a heart failure group (N=238). Spearman correlation analysis was used to test the association of sST2 and NT-proBNP with renal function. The diagnostic value of each biomarker was assessed using receiver operating characteristic (ROC) curves according to 3 different forms: Total group (n=420), non-CKD group (n=217), and CKD group (n=203). RESULTS A striking correlation between eGFR and NT-proBNP (r=-0.525; P<0.001) seemed to be far stronger than that with sST2 (r=-0.147; P<0.05). The optimum cutoff points for sST2 and NT-proBNP to detect HF were 28.960 ng/mL and 1280 pg/mL, respectively, in total, 28.71 ng/mL and 481 pg/mL, respectively, in non-CKD patients, and 30.55 ng/mL and 3314 pg/mL, respectively, in CKD patients. The combined model of sST2 and NT-proBNP was superior to the model of sST2 or NT-proBNP alone, and the difference was statistically significant (P<0.05). CONCLUSIONS The diagnostic value of sST2 is less affected by decreased renal function. sST2 combined with NT-proBNP may improve the diagnostic accuracy of HF.

Topics: Carcinogenesis; Cell Transformation, Neoplastic; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic

Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality.. Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death.. During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models.. The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Topics: Albuminuria; Biomarkers; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high-risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3-point MACE (3P-MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, cardiovascular death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt-1, NT-proBNP, and hs-cTnI, but not other biomarkers, were significantly associated with 3P-MACE, all-cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT-proBNP and hs-cTnI. NT-proBNP and hs-cTnI were also significantly associated with 5P-MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT-proBNP and hs-cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT-proBNP and hs-cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

Topics: Biomarkers; Coronary Artery Disease; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Placenta Growth Factor; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Troponin I

Chronic Kidney Disease (CKD) is independently associated with increased cardiovascular disease (CVD) risk. The aim of this study was to investigate the potential roles of B lymphocyte populations with cardiac remodeling in elderly patients with advanced CKD.. We designed a retrospective study in a cohort of 167 patients (84 advanced CKD patients with stage 4-5 and 83 non-CKD controls). B cell subsets: CD19(+)CD5(+) and CD19(+)CD5(-) B cells were identified by flow cytometry. Correlation of B cells subsets with cardiac remodeling and clinical data in elderly CKD patients were analyzed.. In this study, we found that the prevalence of hypertension was more common in CKD patients than in the control subjects (P < 0.05). Spearman's analysis showed that CD19(+)CD5(+) B cells were negatively correlated with high sensitivity C-reactive protein (hsCRP), β2-microglobulin (β2-MG), serum creatinine (SCr), pro-brain natriuretic peptide (pro-BNP), high-sensitivity troponin T (TNT-hs), left ventricle end-diastolic dimension (LVDD), left ventricle end-systolic dimension (LVSD) and left ventricular mass (LVM), and CD19(+)CD5(-) B cells were negatively correlated with β2-MG, SCr, pro-BNP and TNT-hs (P < 0.05). In contrary, left ventricular ejection fractions (LVEF) was positively correlated with CD19(+)CD5(+) and CD19(+)CD5(-) B cells (P < 0.05). In addition, patients with higher levels of CD19(+)CD5(+) B cells exhibited lower level of pro-BNP, TNT-hs, interventricular septum (IVS), LVSD and LVM (P < 0.05). Higher levels of CD19(+)CD5(-) B cells also presented lower levels of pro-BNP, TNT-hs and LVSD, but higher levels of LVEF (P < 0.05). Cox regression analysis showed that patients with higher levels of LVSD, lower CD19(+)CD5(+)and CD19(+)CD5(-) B cells counts have a higher risk of all-cause mortality (P < 0.05).. Our results showed that CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes were negatively correlated with ventricular hypertrophy-related echocardiographic parameters in advanced CKD patients, which indicated that B lymphocytes might be involved in pathogenesis and improve cardiac remodeling in CKD patients.

Topics: Aged; B-Lymphocyte Subsets; Biomarkers; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Retrospective Studies; Ventricular Remodeling

Chronic kidney disease (CKD) has been associated with adverse clinical outcomes. Hyponatremia, a marker of illness severity and poor prognosis, is commonly exhibited in patients with CKD.. This cross-sectional study included patients hospitalized due to heart failure (HF). We used stepwise logistic regression to investigate the independent association of cardiovascular drugs, markers of HF severity, and baseline clinical characteristics with hyponatremia in three subgroups; normal renal function, mild-to-moderate CKD, and severe CKD.. Of the 1232 patients, 38.6% were hyponatremic. Patients with severe CKD, compared to those with normal renal function and mild-to-moderate CKD, were more likely to be hyponatremic (47.1%, 34.4% and 36.6%, respectively; p ≤ 0.0001). Alcohol consumption, female sex, n-terminal pro-brain natriuretic peptide (NT-proBNP), hydrochlorothiazide (HCT), and mineralocorticoid receptor antagonist (MRA) use, or angiotensin II receptor I blocker (ARB) non-use were associated with hyponatremia in patients with normal renal function (p ≤ 0.03 in all cases). Current smoking, diabetes mellitus, NT-proBNP, loop diuretic dose, and MRA use were predictors in mild-to-moderate CKD (p ≤ 0.04 in all cases). ARB use, loop diuretic dose, and HCT use were predictors in severe CKD (p ≤ 0.03 in all cases). Non-use of dihydropyridine calcium channel blocker (CCB) was an independent predictor of hyponatremia in all CKD stages (p ≤ 0.04 in all cases).. Apart from a firm favorable effect of CCBs, cardiovascular therapy should be carefully tailored to avoid hyponatremia in patients with cardiorenal syndrome.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Calcium Channel Blockers; Cross-Sectional Studies; Dihydropyridines; Female; Heart Failure; Humans; Hydrochlorothiazide; Hyponatremia; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Angiotensin; Renal Insufficiency, Chronic; Sodium Potassium Chloride Symporter Inhibitors

Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality in the ever-growing population of patients with chronic kidney disease (CKD). There is a need to enhance early prediction to initiate treatment in CKD. We sought to study the feasibility of a multi-variable biomarker approach to predict incident HF risk in CKD.. We examined 3182 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) without prevalent HF who underwent serum/plasma assays for 11 blood biomarkers at baseline visit (B-type natriuretic peptide [BNP], CXC motif chemokine ligand 12, fibrinogen, fractalkine, high-sensitivity C-reactive protein, myeloperoxidase, high-sensitivity troponin T (hsTnT), fibroblast growth factor 23 [FGF23], neutrophil gelatinase-associated lipocalin, fetuin A, aldosterone). The population was randomly divided into derivation (n = 1629) and validation (n = 1553) cohorts. Biomarkers that were associated with HF after adjustment for established HF risk factors were combined into an overall biomarker score (number of biomarkers above the Youden's index cut-off value). Cox regression was used to explore the predictive role of a biomarker panel to predict incident HF. A total of 411 patients developed incident HF at a median follow-up of 7 years. In the derivation cohort, four biomarkers were associated with HF (BNP, FGF23, fibrinogen, hsTnT). In a model combining all four biomarkers, BNP (hazard ratio [HR] 2.96 [95% confidence interval 2.14-4.09]), FGF23 (HR 1.74 [1.30-2.32]), fibrinogen (HR 2.40 [1.74-3.30]), and hsTnT (HR 2.89 [2.06-4.04]) were associated with incident HF. The incidence of HF increased with the biomarker score, to a similar degree in both derivation and validation cohorts: from 2.0% in score of 0% to 46.6% in score of 4 in the derivation cohort to 2.4% in score of 0% to 43.5% in score of 4 in the validation cohort. A model incorporating biomarkers in addition to clinical factors reclassified risk in 601 (19%) participants (352 [11%] participants to higher risk and 249 [8%] to lower risk) compared with clinical risk model alone (net reclassification improvement of 0.16).. A basic panel of four blood biomarkers (BNP, FGF23, fibrinogen, and hsTnT) can be used as a standalone score to predict incident HF in patients with CKD allowing early identification of patients at high-risk for HF. Addition of biomarker score to clinical risk model modestly reclassifies HF risk and slightly improves discrimination.

Topics: Adult; Biomarkers; Cohort Studies; Fibrinogen; Fibroblast Growth Factors; Heart Failure; Humans; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Risk Factors

Background Contemporary guidelines recommend using atherosclerotic cardiovascular disease screening tools to guide primary prevention. The performance of these scores is not well known in patients with moderate to advanced chronic kidney disease, particularly in combination with clinically available cardiac biomarkers including N-terminal pro-brain-type natriuretic peptide and high-sensitivity troponin T (hsTnT). Methods and Results We studied 1027 participants from the Chronic Renal Insufficiency Cohort without self-reported atherosclerotic cardiovascular disease who were not taking aspirin or statins at enrollment. Framingham Risk Score, Pooled Cohort Equation, N-terminal pro-brain-type natriuretic peptide, and hsTnT were measured at baseline. Outcomes included fatal and nonfatal myocardial infarction, stroke, and cardiac death. We calculated 10-fold cross-validated Harrell's C-indices for each risk score and cardiac biomarker alone and in combination. The C-index (95% CI) for discrimination of atherosclerotic cardiovascular disease was 0.72 (0.67, 0.77) for the Framingham Risk Score, and 0.72 (0.67, 0.76) for the Pooled Cohort Equation. HsTnT had comparable discrimination to each risk score, and improved the discrimination of each (change in Framingham 0.029, 95% CI 0.003, 0.055; change in Pooled Cohort Equation 0.027, 95% CI 0.002, 0.052). N-terminal pro-brain-type natriuretic peptide had poorer discrimination than the risk scores and did not significantly improve their discrimination (change in Framingham 0.009, 95% CI -0.001, 0.018; change in Pooled Cohort Equation 0.011, 95% CI -0.001, 0.024). Conclusions The Framingham Risk Score and Pooled Cohort Equation demonstrated moderate discrimination for atherosclerotic cardiovascular disease in patients with chronic kidney disease. HsTnT, but not N-terminal pro-brain-type natriuretic peptide, improved their discrimination overall. Until chronic kidney disease-specific atherosclerotic cardiovascular disease risk scores can be developed, it may be worth considering how to incorporate hsTnT into existing clinical risk scores.

Topics: American Heart Association; Atherosclerosis; Biomarkers; Brain; Cardiology; Humans; Kidney; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Risk Assessment; Troponin T

Among patients with chronic kidney disease (CKD), aortic stenosis (AS) is associated with a significantly higher rate of mortality. We aimed to evaluate whether diffuse myocardial fibrosis, determined using native T1 mapping, has prognostic utility in predicting major adverse cardiovascular events (MACEs), including all-cause mortality or heart failure hospitalization, in patients with CKD and severe AS who are evaluated for transcatheter aortic valve implantation. Cardiac magnetic resonance with T1 mapping using the modified Look-Locker inversion recovery technique was performed in 117 consecutive patients with severe AS and CKD (stage ≥3). Patients were followed up to determine the occurrence of MACE. The mean age of the 117 patients in the cohort was 82 ± 8 years. Native T1 was 1,055 ms (25th- to 75th percentiles 1,031 to 1,078 ms), which is higher than previously reported in healthy controls. Patients with higher T1 times were more likely to have higher N-terminal pro-B-type natriuretic peptide levels (4,122 [IQR 1,578 to 7,980] pg/ml vs 1,678 [IQR 493 to 2,851] pg/ml, p = 0.005) and a history of heart failure (33% vs 9%, p = 0.034). After median follow-up of 3.4 years, MACE occurred in 71 patients (61%). The Society of Thoracic Surgeons predicted risk of mortality score (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.02 to 1.12, p = 0.006), native T1 >1,024 ms (HR 2.10, 95% CI 1.09 to 4.06, p = 0.028), and New York Heart Association class (HR 1.56, 95% 1.09 to 2.34, p = 0.016) were independent predictors of MACE. Longer native T1 was associated with MACE occurrence in patients with CKD and severe AS.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Fibrosis; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors

Crescent formation indicates severe glomerular pathology, and hypothyroidism usually predicts poor prognosis for severe diseases. However, the relationship between thyroid function and the progression of chronic kidney disease (CKD) is unclear. This study analysed the prognostic predictive value of the serum free triiodothyronine (FT3) to free thyroxine (FT4) ratio and its correlation with renal function in patients with CKD with crescent formation.. This single-centre study included 162 CKD patients with glomerular crescents confirmed by renal pathology between March 2012 and December 2014. According to the first tertile (0.284) of FT3/FT4 ratio, the patients were divided into high and low FT3/FT4 ratio groups. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of the FT3/FT4 ratio.. The age, haemoglobin, eGFR, urinary albumin-to-creatinine ratio, cardiac troponin T, N-terminal brain natriuretic peptide precursor, FT3, FT4, percentage of total crescents in non-globally sclerotic glomeruli, prevalences of hypertension, moderate to severe renal tubulopathy and crescentic nephritis, and proportion of patients receiving glucocorticoids and immunosuppressants were significantly different between high and low FT3/FT4 ratio groups (P < 0.05). Multivariate Cox regression analysis showed that when compared with patients with a high FT3/FT4 ratio (>0.284), those with intermediate and low FT3/FT4 ratios (≤0.284) had an increased risk of the long-term composite endpoint (P < 0.05 for various adjustment models).. A low FT3/FT4 ratio is associated with increased mortality and worse outcome risk in CKD patients with crescent pathology.

Topics: Albumins; Biomarkers; Creatinine; Humans; Immunosuppressive Agents; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency, Chronic; Retrospective Studies; Thyroid Hormones; Thyroxine; Triiodothyronine; Troponin T

Topics: Cardiovascular Diseases; Humans; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Troponin T

Atrial fibrillation (AF) is common in CKD and associated with poor kidney and cardiovascular outcomes. Prediction models developed using novel methods may be useful to identify patients with CKD at highest risk of incident AF. We compared a previously published prediction model with models developed using machine learning methods in a CKD population.. We studied 2766 participants in the Chronic Renal Insufficiency Cohort study without prior AF with complete cardiac biomarker (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T) and clinical data. We evaluated the utility of machine learning methods as well as a previously validated clinical prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology [CHARGE]-AF, which included 11 predictors, using original and re-estimated coefficients) to predict incident AF. Discriminatory ability of each model was assessed using the ten-fold cross-validated. Using machine learning algorithms, a model that included 12 standard clinical variables and cardiac-specific biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T had moderate discrimination for incident AF in a CKD population.

Topics: Age Factors; Aged; Atrial Fibrillation; Biomarkers; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Likelihood Functions; Machine Learning; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Race Factors; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Troponin T

Topics: Aged; Blood Flow Velocity; Body Composition; Case-Control Studies; Echocardiography, Doppler; Electric Impedance; Exercise Test; Exercise Tolerance; Female; Functional Status; Galectin 3; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Mitral Valve; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Phenotype; Quality of Life; Renal Insufficiency, Chronic; Stroke Volume

Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD.. We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors.. In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08-1.40]}, QRS [OR 1.28 (95% CI 1.16-1.42)] and QTc [OR 1.94 (95% CI 1.50-2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06-1.16)] and QTc [OR 1.82 (95% CI 1.58-2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters.. hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.

Topics: Atrial Fibrillation; Biomarkers; Cross-Sectional Studies; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

We hypothesized that arterial function and N-terminal natriuretic peptide (NT-proBNP) levels as a marker of volume overload, relate differently to E/e' as an index of diastolic function in dialysis compared with non-dialysis patients with chronic kidney disease. We further examined whether cardiovascular risk factors attenuated these relationships.. We assessed cardiovascular risk factors and determined arterial function indices by applanation tonometry using SphygmoCor software and E/e' by echocardiography in 103 (62 non-dialysis and 41 dialysis) patients.. In established confounder adjusted analysis, dialysis status impacted the pulse wave velocity-E/e' relationship (interaction p = .01) but not the NT-proBNP level-E/e' association (interaction p = .1). Upon entering arterial function measures and NT-proBNP levels simultaneously in regression models, arterial function measures were associated with E/e' (p = .008 to .04) in non-dialysis patients whereas NT-proBNP levels were related to E/e' in dialysis patients (p = .009 to .04). Bivariate associations were found between diabetes (p < .0001) and E/e' in non-dialysis patients, and haemoglobin concentrations and E/e' (p = .02) in those on dialysis. Upon adjustment for diabetes in non-dialysis patients, only central pulse pressure remained associated with E/e' (p = .02); when haemoglobin concentrations were adjusted for in dialysis patients, NT-proBNP levels were no longer associated with E/e' (p = .2). In separate models, haemoglobin levels were associated with E/e' independent of left ventricular mass index and preload and afterload measures (p = .02 to .03).. The main determinants of E/e' may differ in non-dialysis compared with dialysis patients. These include arterial function and diabetes in non-dialysis patients, and volume overload and anaemia in dialysis patients.

Topics: Blood Pressure; Cardiovascular Diseases; Dialysis; Diastole; Echocardiography; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Pulse Wave Analysis; Renal Dialysis; Renal Insufficiency, Chronic; ROC Curve; Ventricular Function, Left

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of the composite renal endpoint and weakens the progressive decline in renal function in patients with chronic heart failure (HF). However, a detailed mechanism of SGLT2i on renal function and outcome remains uninvestigated.. We prospectively included 40 type 2 diabetic mellitus (T2DM) patients (median 68 years old, 29 male) who were hospitalized for decompensated HF and received SGLT2i during the index hospitalization. Of them, 24 patients had increases in estimated glomerular filtration rate (eGFR) at 12-month follow-up and 16 had decreases in eGFR. We investigated the baseline factors associating with the improvement in renal function.. Lower plasma B-type natriuretic peptide (BNP) level and the use of renin-angiotensin system inhibitor (RASI) were independently associated with increases in eGFR during the follow-up period (p < 0.05 for both). Patients with both low plasma BNP levels and uses of RASI achieved significant increases in eGFR irrespective of the baseline HbA1c levels.. Lower plasma BNP level and the use of RASI at baseline were the key factors contributing to the renoprotective effects of SGLT2i among patients with decompensated HF and T2DM.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Diabetes Mellitus, Type 2; Disease Progression; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Recovery of Function; Registries; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome

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 ability of most biomarkers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), to predict prognosis in heart failure can be affected by the state of renal function; therefore, there is the need for a biomarker that can predict prognosis accurately without the influence of renal function. The prognostic value of cysteine-rich protein 61 (CYR61/CCN1) in acute heart failure (AHF) patients has been proven.. A total of 248 patients hospitalized with AHF were recruited in this study, and serum CCN1 levels, NT-proBNP levels, and other necessary data of patients were collected upon admission. The correlation of serum CCN1 with estimated glomerular filtration rate (eGFR) was investigated, and the logistic regression model was used to investigate the prognostic value of serum CCN1 for 3-month mortality.. Fifty-four of 248 patients died (21.8%) during a 3-month follow-up. Serum CCN1 had no significant correlation with eGFR (rho = -0.088, p = 0.167). In the overall population and patients without chronic kidney disease, results showed that both serum CCN1 and NT-proBNP were significantly associated with 3-month mortality. In patients with chronic kidney disease, serum CCN1 was significantly associated with 3-month mortality in logistic regression analysis (odds ratio = 2.40, p = 0.002) while NT-proBNP was not. Further in tertile group comparison, in patients with chronic kidney disease, higher tertile levels of serum CCN1 had a significantly higher risk of 3-month mortality compared to the lower tertile ones (odds ratio = 4.17, p = 0.013), but that of NT-proBNP did not.. Serum CCN1 level is not associated with eGFR, and it maintains the prognostic value in AHF patients with chronic kidney disease. CCN1 could be a potential novel prognostic biomarker in AHF patients with chronic kidney disease.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; China; Cysteine-Rich Protein 61; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renal Insufficiency, Chronic

Elevated serum uric acid (UA) is associated with an increased risk of cardiovascular disease and worse clinical outcome in patients with cardiovascular disease. Nevertheless, the prognostic value of serum UA level in hospitalized heart failure patients with preserved ejection fraction (HFpEF) has not been fully elucidated. The aim of this study was to investigate whether serum UA level on admission could be associated with subsequent mortality in hospitalized patients with HFpEF. We examined 516 consecutive hospitalized HFpEF (left ventricular ejection fraction ≥50%) patients with decompensated heart failure from our HFpEF-specific multicenter registry who had serum UA data on admission. The primary outcome of interest was all-cause death. During a median follow-up period of 749 (interquartile range 540 to 831) days, 90 (17%) patients died. Higher serum UA level was significantly related to increased incidence of all-cause death (p = 0.016). In addition, patients with higher serum UA (≥6.6 mg/dl, median) and plasma B-type natriuretic peptide (≥401.2 pg/ml, median) levels had the highest incidence of all-cause death in the groups (p = 0.002). In multivariable Cox regression analysis, serum UA was an independent determinant of mortality (hazards ratio 1.23, 95% confidence interval 1.10 to 1.39) even after adjustment for prespecified confounders, renal function and the use of diuretics before admission. In conclusions, higher admission serum UA was an independent determinant of mortality in hospitalized HFpEF patients. Our findings indicate the importance of assessing admission serum UA level for further risk stratification in hospitalized patients with HFpEF.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Cause of Death; Comorbidity; Female; Heart Failure; Hospitalization; Humans; Japan; Male; Mineralocorticoid Receptor Antagonists; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Registries; Renal Insufficiency, Chronic; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Uric Acid

Pathophysiological cardiac and renal interactions are termed cardiovascular-renal disorder (CvRD). Cardiovascular disease/dysfunction secondary to kidney disease (CvRD

Topics: Animals; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Clusterin; Cystatin B; Dog Diseases; Dogs; Echocardiography; Female; Glomerular Filtration Rate; Lipocalin-2; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Troponin I

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Romania; ST Elevation Myocardial Infarction

This study aimed to elucidate the influential parameter, acquired from the analyses of nasal capnography waveforms, for the elevated plasma brain natriuretic peptide (BNP) levels in patients (n = 34) with heart failure (HF). The capnography waveforms were analyzed to evaluate changes in end-tidal CO

Topics: Aged; Aged, 80 and over; Capnography; Exhalation; Female; Heart Failure; Humans; Inhalation; Lung; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Insufficiency, Chronic; Severity of Illness Index; Time Factors; Up-Regulation

Background The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF-15 (growth differentiation factor-15), galectin-3, sST2 (soluble suppression of tumorigenesis-2), hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross-sectional and longitudinal KCCQ scores. Among 2873 participants, GDF-15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19-1.68) and galectin-3 (1.28; 1.12-1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT-proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF-15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12-1.65), hsTnT (1.20; 1.01-1.44), and NT-proBNP (1.30; 1.08-1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin-3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF

Topics: Adult; Aged; Biomarkers; Blood Proteins; Cross-Sectional Studies; Female; Galectins; Growth Differentiation Factor 15; Health Status Indicators; Heart Failure; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Surveys and Questionnaires; Time Factors; Troponin T; United States

This was an investigation of the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and mortality in patients with stage 3-4 chronic kidney disease (CKD).. This study was designed as a subgroup analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) study. The HAPPY study included 4650 randomly selected individuals from the 7 geographical regions of Turkey. A total of 191 subjects from the original cohort with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.1.73 m² were enrolled in this study and the relationship between NT-proBNP and mortality was investigated. Prognostic variables for total and cardiovascular mortality were also examined using Cox regression analysis.. The mean length of follow-up was 76.12±22.45 months. The mean NT-proBNP level was 423.54±955.88 pg/mL. During follow-up, 51 subjects (26.7%) died from any cause and 36 subjects (18.8%) died from a cardiovascular cause. The presence of hypertension (hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.01-3.50; p=0.048), anemia (HR: 2.49; 95% CI: 1.20-5.15; p=0.014), male gender (HR: 2.64; 95% CI: 1.44-4.86; p=0.002) and log NT-proBNP (HR: 4.93; 95% CI: 2.83-8.58; p<0.001) were independent variables for total mortality. The presence of hypertension (HR: 2.47; 95% CI: 1.09-5.56; p=0.029), male gender (HR: 2.79; 95% CI: 1.38-5.62; p=0.004), eGFR (HR: 0.94; 95% CI: 0.91-0.98; p=0.005) and log NT-proBNP (HR: 6.31; 95% CI: 3.11-12.81; p<0.001) were independent predictors of cardiovascular mortality.. NT-proBNP was found to be an independent prognostic marker in patients with stage 3-4 CKD.

Topics: Aged; Anemia; Biomarkers; Cause of Death; Confidence Intervals; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Regression Analysis; Renal Insufficiency, Chronic; Sex Factors; Turkey

Topics: Age Factors; Female; Global Health; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Renal Insufficiency, Chronic; Sex Factors; Turkey

Topics: Adult; Aged; Autopsy; Betacoronavirus; Biomarkers; Cardiovascular Diseases; Cell Death; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Endothelium; Female; Heart; Humans; Lymphopenia; Male; Microscopy, Electron; Middle Aged; Muscle Cells; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Obesity; Pandemics; Pneumonia, Viral; Renal Insufficiency, Chronic; SARS-CoV-2; Troponin I

Patients with advanced chronic kidney disease (CKD stage 4-5) have an increased risk of death. To study the determinants of all-cause mortality, we recruited 210 consecutive CKD stage 4-5 patients not on dialysis to the prospective Chronic Arterial Disease, quality of life and mortality in chronic KIDney injury (CADKID) study.. One hundred seventy-four patients underwent maximal bicycle ergometry stress testing and lateral lumbar radiography to study abdominal aortic calcification score and echocardiography. Carotid and femoral artery intima-media thickness and elasticity and brachial artery flow-mediated dilatation were measured in 156 patients.. The duration of follow-up was 42 ± 17 months (range 134-2,217 days). The mean age was 61 ± 14 years, and the estimated glomerular filtration rate was 12 (11-15) mL/min/1.73 m2. Thirty-six (21%) patients died during follow-up (time to death 835 ± 372 days). Seventy-five and 21 patients had diabetes and coronary artery disease, respectively, and all but one had hypertension. In the respective multivariate proportional hazards models adjusted for age, sex, and coronary artery disease, the significant determinants of mortality were troponin T, N-terminal pro-B-type natriuretic peptide, maximal ergometry performance, abdominal aortic calcification score, E/e' ratio, and albumin.. Stress ergometry performance, abdominal aortic calcification score, E/e' of echocardiography, and plasma cardiac biomarkers and albumin predict mortality in advanced CKD.

Topics: Aged; Biomarkers; Carotid Intima-Media Thickness; Coronary Artery Disease; Echocardiography; Exercise Test; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Troponin T; Vascular Calcification

Topics: Betacoronavirus; Biomarkers; Child; Coronavirus Infections; COVID-19; Heart Diseases; Heart Failure; Humans; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Neoplasms; Pandemics; Peptide Fragments; Pneumonia, Viral; Renal Insufficiency, Chronic; SARS-CoV-2; Troponin I; Troponin T; Virus Diseases

Increased levels of cardiac troponins (cTn) are a hallmark of acute myocardial infarction (AMI), along with symptoms and electrocardiographic (ECG) changes. Stably elevated cTn concentrations are frequently observed in asymptomatic patients with chronic kidney disease (CKD) and/or on hemodialysis (HD); the meaning of this elevation, as assessed by conventional techniques, remains unclear. Aim of our study was to evaluate the clinical significance of cTnI levels in asymptomatic HD patients by employing a newer high-sensitive cTnI (hs-cTnI) assay.. We enrolled 49 patients undergoing regular HD treatment for more than 3 months; all patients were asymptomatic for chest pain and had no history of acute coronary syndrome in the past 2 months. For every patient we measured hs-cTnI, cTnI and brain natriuretic peptide (BNP) before initiation of one HD session at baseline (T0), after 3 (T1) and 9 months (T2). Demographic, anamnestic, dialytic and echocardiographic characteristics of the examined population were evaluated. We also recorded the number of cardiovascular events from T0 to 12 months after T2.. Fifteen patients were lost to follow-up: 6 died, 2 underwent kidney transplantation, 7 did not match the inclusion criteria later during observation. At T0 (49 patients) we observed 14 hs-cTnI positive patients vs. 4 standard c-TnI positive patients (28,5% vs 8,1%); at T1 (40 patients) 16 vs 3 (26.4% vs 7.5%); at T2 (34 pz) 9 vs 0 (26.4% vs 0%). During the study we recorded 10 cardiovascular events, 8 of which in patients that were hs-cTNI positive, leading to death in 3. Hs-cTnI levels were predictive of cardiovascular events at all times and predictive of cardiovascular mortality at T0 and T1 (p < 0.001). In a multivariate analysis, a history of coronary artery disease (CAD) was an independent variable of high hs-cTnI levels at T0 (p < 0.04) and T1 (p < 0.03).. Our study shows that a novel sensitive assay detects more asymptomatic HD patients compared to previously used methods, being at the same time predictive of cardiovascular mortality and morbidity. The only independent variable of high hs-cTnI concentrations was a positive history of cardiovascular disease, suggesting a possible role of hs-cTnI in identifying a high-risk subset of patients.

Topics: Aged; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Time Factors; Troponin I

Chronic fluid overload is common in patients with chronic kidney disease (CKD) and can with time lead to poor prognosis regarding to the cardiovascular events. Serum NT-proBNP and OH/ECW might reflect fluid status of the patients, and the maximal tricuspid regurgitation velocity (TRVmax) could reflect systolic pulmonary artery pressure (SPAP). We investigated the relationship between markers of volume status and marker of pulmonary hypertension (PH) in non-dialysis CKD5 (CKD5-ND) patients.. Bioimpedance spectroscopy (BIS), echocardiography, and measurement of serum NT-proBNP were performed in 137 consecutive patients on the same day. TRVmax greater than or equal to 2.9 m/s, corresponding to SPAP of approximately 36 mmHg, was used as a definition of the possibility of PH in the absence of left heart disease and chronic respiratory disease (PH group).. Patients with possibility of PH (TRVmax ≥ 2.9 m/s) was found in 27 (19.70%) patients. Among the values obtained from BIS, those reflecting the fluid balance (OH, OH/ECW, and E/I ratio) were significantly higher in the PH group. The OH/ECW in patients with PH were significantly higher than those patients without (26.76 ± 15.07 vs. 13.09 ± 15.05, P < 0.001). NT-proBNP was also significantly higher in PH group compared to the non-PH group (median = 10,112 pg/ml, IQR = 30,847 pg/ml vs. median = 1,973 pg/ml, IQR = 7,093 pg/ml, P < 0.001). OH/ECW was positively associated with TRVmax (r = 0.235, P = 0.006). Multivariate logistic regression revealed that increased OH/ECW and serum NT-proBNP were significantly associated with an increased risk of PH.. A significant number of patients showed increased TRVmax, which was closely related to volume status in CKD5-ND patients. Echocardiography and BIS could be important players in a high possibility of PH detection and treatment in asymptomatic CKD patients. Therefore, these measures could be helpful to improve the cardiac outcomes after initiating renal replacement therapy. Further research may be needed to validate the consistency of this association across other stages of CKD.

Topics: Adult; Aged; Biomarkers; Dielectric Spectroscopy; Echocardiography; Female; Humans; Hypertension, Pulmonary; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Water-Electrolyte Balance

Iron deficiency (ID) is common in heart failure (HF) patients and negatively impacts symptoms and prognosis. The aetiology of ID in HF is largely unknown. We studied determinants and the biomarker profile of ID in a large international HF cohort.. We studied 2357 worsening HF patients from the BIOSTAT-CHF cohort. ID was defined as transferrin saturation <20%. Univariable and multivariable logistic regression models were constructed to identify determinants for ID. We measured 92 cardiovascular markers (Olink Cardiovascular III) to establish a biomarker profile of ID. The primary endpoint was the composite of all-cause mortality and first HF rehospitalization. Mean age (±standard deviation) of all patients was 69 ± 12.0 years, 26.1% were female and median N-terminal pro B-type natriuretic peptide levels (+interquartile range) were 4305 (2360-8329) ng/L. Iron deficiency was present in 1453 patients (61.6%), with highest prevalence in females (71.1% vs. 58.3%; P < 0.001). Independent determinants of ID were female sex, lower estimated protein intake, higher heart rate, presence of peripheral oedema and orthopnoea, chronic kidney disease, lower haemoglobin, higher C-reactive protein levels, lower serum albumin levels, and P2Y12 inhibitor use (all P < 0.05). None of these determinants were sex-specific. The biomarker profile of ID largely consisted of pro-inflammatory markers, including paraoxonase 3 (PON3) and tartrate-resistant acid phosphatase type 5. In multivariable Cox proportional hazard regression analyses, ID was associated to worse outcome, independently of predictors of ID (hazard ratio 1.25, 95% confidence interval 1.06-1.46; P = 0.007).. Our data suggest that the aetiology of ID in worsening HF is complex, multifactorial and seems to consist of a combination of reduced iron uptake (malnutrition, fluid overload), impaired iron storage (inflammation, chronic kidney disease), and iron loss (antiplatelets).

Topics: Aged; Anemia, Iron-Deficiency; Aryldialkylphosphatase; Biomarkers; Body Fluids; Eating; Female; Heart Failure; Humans; Inflammation; Iron Deficiencies; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Platelet Aggregation Inhibitors; Prevalence; Prognosis; Proteins; Renal Insufficiency, Chronic; Stroke Volume; Tartrate-Resistant Acid Phosphatase; Transferrin

Increases in cardiac and stress biomarkers may be associated with loss of kidney function through shared mechanisms involving cardiac and kidney injury. We evaluated the associations of cardiac and stress biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), soluble ST-2 (sST-2)] with progression of chronic kidney disease (CKD).. We included 3664 participants with CKD from the Chronic Renal Insufficiency Cohort study. All biomarkers were measured at entry. The primary outcome was CKD progression, defined as progression to end-stage renal disease (ESRD) or 50% decline in estimated glomerular filtration rate (eGFR). Cox models tested the association of each biomarker with CKD progression, adjusting for demographics, site, diabetes, cardiovascular disease, eGFR, urine proteinuria, blood pressure, body mass index, cholesterol, medication use, and mineral metabolism.. There were 1221 participants who had CKD progression over a median (interquartile range) follow-up of 5.8 (2.4-8.6) years. GDF-15, but not sST2, was significantly associated with an increased risk of CKD progression [hazard ratios (HRs) are per SD increase in log-transformed biomarker]: GDF-15 (HR, 1.50; 95% CI, 1.35-1.67) and sST2 (HR, 1.07; 95% CI, 0.99-1.14). NT-proBNP and hsTnT were also associated with increased risk of CKD progression, but weaker than GDF-15: NT-proBNP (HR, 1.24; 95% CI, 1.13-1.36) and hsTnT (HR, 1.11; 95% CI, 1.01-1.22).. Increases in GDF-15, NT-proBNP, and hsTnT are associated with greater risk for CKD progression. These biomarkers may inform mechanisms underlying kidney injury.

Topics: Biomarkers; Cardiovascular Diseases; Cohort Studies; Disease Progression; Female; Glomerular Filtration Rate; Growth Differentiation Factor 15; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Troponin T

Topics: Aged; Bayes Theorem; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Hepatitis A Virus Cellular Receptor 1; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

Since the introduction of sacubitril/valsartan in clinical cardiology, neprilysin has become a major target for heart failure treatment. Plasma neprilysin concentration has been discussed as a novel biomarker that predicts cardiac events. Natriuretic peptides may inhibit plasma neprilysin. As they accumulate in chronic kidney disease (CKD), we hypothesized that high plasma neprilysin loses its predictive role in CKD patients.. We measured plasma levels of neprilysin concentration, neprilysin activity and brain natriuretic peptide (BNP) in 542 CKD G2-G4 patients within the CARE FOR HOMe study. Patients were followed for predefined endpoints of hospitalization for acute decompensated heart failure and incident atherosclerotic cardiovascular events.. During 5.1 ± 2.1 years, 63 patients had acute decompensated heart failure and 125 patients had incident atherosclerotic cardiovascular events. In both Kaplan-Meier and multivariate Cox regression analyses, high plasma BNP and low, rather than elevated, neprilysin activity predicted future hospitalization for acute decompensated heart failure; neprilysin concentration was not predictive. Furthermore, only BNP was an independent predictor of incident atherosclerotic cardiovascular events.. In line with experimental studies, high natriuretic peptides may inhibit neprilysin activity in CKD. Therefore, high neprilysin activity and concentrations are not predictors of adverse cardiovascular outcome in CKD patients. Thus neprilysin inhibitors should be implemented with caution in patients with advanced CKD.

Topics: Aged; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Renal Insufficiency, Chronic

Topics: Aged; Biomarkers; Endothelin-1; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Stroke Volume

Topics: Hospitalization; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Sepsis

The risk of cardiovascular (CV) complications is much greater in patients with chronic kidney disease (CKD). The aim of this study was to assess predictors of mortality, renal failure progression, and the need for dialysis in patients with CKD.. The study group consisted of 70 patients with stage 3-5 CKD, followed up on average for 33.4 ± 15.6 months. Laboratory tests and echocardiography were performed on all patients. Composite endpoints were defined as (1) all-cause mortality and (2) mortality or renal replacement therapy (RRT), defined as the initiation of dialysis therapy.. During the observation period, 13 patients died and 11 began dialysis therapy. NT-proBNP was found to be a significant predictor in receiver operating characteristic curve analysis for all study endpoints. The optimal cutoff value for NT-proBNP as a predictor of mortality was 569.8 pg/mL, with a sensitivity of 53.8% and a specificity of 89.1%. For mortality or RRT, the cutoff value for NT-proBNP was 384.9 pg/mL, with a sensitivity and specificity of 70.8 and 72.7%, respectively. In a multivariate regression analysis, NT-proBNP was an independent predictor of mortality with an OR = 7.5 (95% CI: 1.05-53.87; p = 0.044) and of mortality or RRT with an OR = 4.7 (95% CI: 1.01-22.66; p = 0.048).. NT-proBNP is an independent predictor of mortality in patients with CKD and can also be useful for CV risk stratification in this patient population.

Topics: Aged; Biomarkers; Cause of Death; Disease Progression; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Prognosis; Protein Precursors; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk Assessment; ROC Curve; Survival Rate; Time Factors

Various epidemiological studies linked high fibroblast growth factor 23 (FGF23) levels with cardiovascular events in chronic kidney disease (CKD). It remains enigmatic whether high FGF23 exerts adverse cardiovascular effects, or whether it reflects detrimental effects of residual confounders. Earlier studies adjusted for CKD-mineral bone disease (CKD-MBD) regulators of FGF23 rather than for recently discovered non-CKD-MBD regulators, among which iron deficiency and heart failure are of particular importance. Moreover, they used c-terminal FGF23 (cFGF23) assays rather than more specific intact FGF23 (iFGF23) assays.. The CARE FOR HOMe study analyzed plasma ferritin, iFGF23, cFGF23 and N-terminal proBNP (NT-proBNP) along with conventional risk factors, among 575 CKD G2-G4 patients to determine the interaction between FGF23, its non-CKD-MBD regulators, and incident cardiovascular events in CKD patients. The participants were followed up for 5.1 ± 2.1 years for the occurrence of atherosclerotic events and hospitalization for acute decompensated heart failure.. cFGF23 correlated strongly with high iFGF23 (r = 0.607), fairly with high NT-proBNP (r = 0.453) and weakly with low ferritin (r = -0.207); correlation coefficients of iFGF23 with NT-proBNP and ferritin were numerically lower. In Kaplan-Meier analyses, both endpoints were predicted by cFGF23 and iFGF23. In Cox regression models, cFGF23 remained an outcome predictor after adjustment for conventional risk factors and ferritin. This prediction was largely eliminated when further adjusting for NT-proBNP. iFGF23 was less consistently associated with adverse outcome in partly adjusted models, and failed to predict outcome in fully adjusted models.. In summary, iron deficiency and heart failure affect plasma FGF23. As adjustment for NT-proBNP virtually eliminates the association between plasma FGF23 and predefined outcome, we speculate that high FGF23, rather than exerting detrimental cardiovascular effects, mirrors prevalent heart disease.

Topics: Aged; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors

Background Tissue inhibitor of metalloproteinases-1 ( TIMP -1) and procollagen type III aminoterminal peptide are established circulating markers of extracellular matrix remodeling and associated with cardiovascular disease. The association of both biomarkers with incident congestive heart failure and chronic kidney disease ( CKD ) in the community is not well studied. Methods and Results We measured plasma total TIMP -1 and procollagen type III aminoterminal peptide levels in 922 Framingham participants (mean age, 57 years; 57% women) and related both biomarkers to the risk of incident CKD and congestive heart failure in multivariable-adjusted Cox regression models. Plasma total TIMP -1 levels were positively associated with risk of incident CKD (164 events; hazard ratio per 1 SD in log-biomarker, 1.90; 95% CI , 1.53-2.37) in multivariable models, including adjustments for left ventricular mass, C-reactive protein, and B-type natriuretic peptide levels. The association of total TIMP -1 with risk of congestive heart failure was statistically significant in an age- and sex-adjusted model, but was attenuated upon adjustment for conventional risk factors. Blood procollagen type III aminoterminal peptide levels were not related to the risk of CKD or congestive heart failure. Conclusions Higher baseline levels of total TIMP -1 conferred an increased risk for incident CKD , independent of conventional risk factors and circulating biomarkers of chronic systemic inflammation and neurohormonal activation. Our prospective observations in a large community-based sample support the role of matrix remodeling in the pathogenesis of CKD .

Topics: Aged; C-Reactive Protein; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Tissue Inhibitor of Metalloproteinase-1; United States

Growth differentiation factor-15 (GDF-15) is a stress-inducible cytokine and member of the transforming growth factor-β cytokine superfamily that refines prognostic assessment in subgroups of patients with heart failure (HF). We evaluated its role in HF patients with chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min/1.73 m. A total of 358 patients with stable systolic HF were followed for a median of 1121 (interquartile range, 379-2600) days. Comprehensive evaluation including B-type natriuretic peptide (BNP) and GDF-15 testing was performed at study entry; the analysis was stratified according to kidney function.. Patients with CKD (33.8%) were older, had more often diabetes, and were less often treated with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). GDF-15 was associated with estimated glomerular filtration rate, whereas BNP was associated with left ventricular-end diastolic diameter and ejection fraction (P < 0.01). During follow-up, 244 patients (68.2%) experienced an adverse outcome (death, urgent transplantation, implantation of mechanical circulatory support). In patients with HF and CKD, the Cox proportional hazard model identified BNP, GDF-15, sex, systolic blood pressure, sodium, total cholesterol, and ACEi/ARB treatment as significant variables associated with an adverse outcome (P < 0.05). In multivariable analysis, BNP was replaced by GDF-15. Net reclassification improvement confirmed prognostic superiority of the model encompassing GDF-15 (GDF-15, sodium, total cholesterol, ACEi/ARB treatment) compared with the model without GDF-15 (BNP, sex, sodium, ACEi/ARB treatment), net reclassification improvement 0.62, P = 0.005. In contrast, in patients with HF and normal kidney function, BNP remained superior to GDF-15 in a multivariable model.. In patients with systolic HF and CKD, GDF-15 is more strongly associated with adverse outcomes than the conventionally used BNP.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Pressure; Cholesterol; Female; Follow-Up Studies; Glomerular Filtration Rate; Growth Differentiation Factor 15; Heart Failure, Systolic; Heart Transplantation; Heart-Assist Devices; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Renal Insufficiency, Chronic; Sex Factors; Sodium; Systole

Topics: Aged; Atrial Fibrillation; China; Chronic Disease; Cognitive Dysfunction; Coronary Artery Disease; Diabetes Mellitus; Female; Heart Failure; Hospitalization; Humans; Hypertension; India; Malaysia; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Singapore; Smoking; Stroke; Troponin T

Chronic kidney disease (CKD) promotes hypertrophy and fibrosis in heart, and increases the risk of cardiovascular mortality. Ferric citrate is a dietary phosphate binder used to control hyperphosphatemia in CKD patients. It has been shown to raise iron stores, improve anemia and secondary hyperparathyroidism, and decrease vascular calcification in CKD patients. The present study was done to explore the effects and mechanism of actions of ferric citrate on cardiac hypertrophy and fibrosis.. Male SD rats were randomized to CKD (5/6 nephrectomized) and sham-operated control groups. CKD rats were fed regular diet or a diet containing 4% ferric citrate. After 8 weeks, hemoglobin, renal function and cardiovascular endpoints including blood pressure, heart/body weight ratio, serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiac histology and markers of hypertrophy, fibrosis and inflammation were assessed.. Compared to the controls, untreated CKD group exhibited hypertension, elevated serum urea, creatinine, phosphate, and NT-proBNP concentrations, anemia, cardiomegaly ,cardiac hypertrophy and fibrosis. Treatment with ferric citrate significantly increased hemoglobin and serum iron concentrations, reduced serum phosphate and NT-proBNP levels and ameliorated hypertension, heart/body weight ratio, cardiac hypertrophy, fibrosis and inflammation. In addition, ferric citrate administration reduced the size of cardiomyocytes and expressions of myocardin, transforming growth factor-β, interleukin-6 and monocyte chemotactic protein 1.. Treatment with ferric citrate attenuated renal failure and cardiovascular abnormalities including myocardial hypertrophy and fibrosis in CKD rats.

Topics: Animals; Biomarkers; Cardiomegaly; Ferric Compounds; Fibrosis; Iron; Male; Natriuretic Peptide, Brain; Peptide Fragments; Phosphates; Random Allocation; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic

Topics: Acute Kidney Injury; Animals; Arginine; Cardiomegaly; Disease Models, Animal; Disease Progression; Down-Regulation; Enzyme Activation; Fibrosis; HSP90 Heat-Shock Proteins; Male; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Phosphorylation; Rats, Wistar; Renal Insufficiency, Chronic; Threonine; Time Factors

N-terminal proB-type natriuretic peptide (NT-proBNP) may be a useful marker in canine leishmaniosis (CanL). The aim was to compare NT-proBNP in dogs at different LeishVet stages of CanL and with idiopathic chronic kidney disease (CKD). Dogs diagnosed with CanL or CKD and a group of healthy dogs were included (group A, five normal dogs; group B, six dogs LeishVet 1-2; group C, 13 dogs LeishVet 3-4; group D, six dogs with CKD). NT-proBNP was higher (P<0.001) in group C (7.616 pmol/l, interquartile range (IQR) 3537-10,000 pmol/l) than in group A (293 pmol/l, IQR 257-373), group B (388.5 pmol/l, IQR 324-793) and group D (740 pmol/l, IQR 557-962 pmol/l). International Renal Interest Society (IRIS) kidney stage was not different between groups C and D or between groups A and B, but was different within all the rest of the group comparisons (P<0.001). In group C all dogs had echocardiographic increase in left ventricular mass index. NT-proBNP had negative correlation with haematocrit (P<0.001, r=0.749) and positive correlation with systemic blood pressure (P<0.001, r=0.728). NT-proBNP is consistently elevated in dogs with advanced CanL and is strongly correlated with the degree of systemic hypertension and anaemia. Moreover, dogs with advanced CanL exhibit increase in left ventricular mass. NT-proBNP may however be a less desirable cardiac marker as unlike cardiac troponin I it is often not elevated at earlier stages of CanL.

Topics: Animals; Biomarkers; Dog Diseases; Dogs; Female; Humans; Leishmaniasis, Visceral; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

Novel biomarkers might improve the prediction of mortality in hemodialysis (HD) patients. We simultaneously measured the levels of conventional and novel biomarkers [serum N-terminal pro-brain natriuretic peptide (NT-proBNP), intact fibroblast growth factor-23 (FGF23), β2-microglobulin (β2MG), cystatin C, and high-sensitivity C-reactive protein (hsCRP)] in 307 prevalent Japanese HD patients. There were 66 all-cause deaths, and 25 cardiovascular (CV) deaths during 2 years, which were assessed using Cox models and concordance (C)-statistics. The addition of NT-proBNP alone (P < 0.05) or NT-proBNP, hsCRP, and β2MG as a panel (C-statistics: 0.834 vs. 0.776, P < 0.01) to a conventional risk model composed of age, diabetes, and the serum albumin level significantly improved the prediction of 2-year all-cause mortality, and the addition of NT-proBNP and hsCRP as a panel to a conventional risk model composed of age significantly improved the prediction of 2-year CV mortality (P < 0.05) in Japanese prevalent HD patients. Neither FGF23 nor cystatin C improved mortality prediction.

Topics: Aged; beta 2-Microglobulin; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cystatin C; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Japan; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors

To investigate the correlation between elevated serum sclerostin levels and chronic kidney disease outcomes for patients receiving peritoneal dialysis (PD).. We performed a prospective observational study in stable PD patients. Serum sclerostin levels were determined via enzyme immunoassay, and median levels of sclerostin were used to divide patients into high and low sclerostin groups. New-onset cardiovascular events (CVEs) and cardiovascular mortality were evaluated during a 6-year follow-up period.. Ninety-eight patients [mean age 52.5 ± 10.9 years, 49% males, 21.4% diabetic, median dialysis vintage 40.7 (range 17.9-72.2) months] were recruited. Compared with those in the low sclerostin group, patients in the high sclerostin group demonstrated higher levels of total-cholesterol, NT-proBNP, and osteoprotegerin (all P < 0.05). During the 6-year study period, 25 CVEs and 17 cardiovascular deaths occurred in the high sclerostin group, whereas 11 CVEs and four cardiovascular deaths occurred in the low sclerostin group. A Cox regression analysis determined that high sclerostin levels significantly increased the risk for CVEs (HR 2.475, 95% CI 1.116-5.489, P = 0.026) and cardiovascular death (HR 3.484, 95% CI1.134-10.706, P = 0.029), after multiple adjustments were made.. Our data suggest that high sclerostin levels may predict the onset of CVEs and cardiovascular mortality among PD patients.

Topics: Adaptor Proteins, Signal Transducing; Adult; Bone Morphogenetic Proteins; Cardiovascular Diseases; Cholesterol; Female; Follow-Up Studies; Genetic Markers; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Peritoneal Dialysis; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors

This study is the first of its kind to examine the impact of the Ramadan fasting on hydration status, plasma brain natriuretic peptide (BNP) levels, and kidney function in chronic kidney disease (CKD) patient.. This prospective cohort study included 2 groups of patients with CKD grades 2-4: thirty-one Muslim patients who fasted the month of Ramadan (fasting group) and 26 Muslim patients who did not fast (control group). One week before the Ramadan fast, in the last week of the month of Ramadan (4 weeks), and 4 weeks after the end of the Ramadan month (8 weeks), hydration status and blood analysis of urea, creatinine and BNP levels were measured.. Among fasting patients, serum urea levels increased significantly (p = 0.024) during the last week of fasting and returned to basal levels at 4 weeks after the end of the Ramadan month, the estimated glomerular filtration rate did not change significantly at the end of fasting (p = 0.411), the hydration status indices and plasma BNP levels were significantly decreased after fasting (p ≤ 0.021) but returned to basal values 4 weeks thereafter.. Patients with CKD grades 2-4 can fast throughout the month of Ramadan with no significant deterioration of renal functions and with a reasonable degree of safety.

Topics: Adult; Aged; Blood Urea Nitrogen; Cohort Studies; Creatinine; Fasting; Female; Glomerular Filtration Rate; Humans; Islam; Israel; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Organism Hydration Status; Prospective Studies; Renal Insufficiency, Chronic

Plasma content of copeptin increases with the advancement of chronic kidney disease (CKD). The purpose of this study was to evaluate copeptin content as a potential marker of CKD, as a single pathology or with coexisting heart failure. Seventy-six patients were divided into the following groups: Group 1 (control), without CKD and heart failure; Group 2, CKD stage 3a; Group 3, CKD stage 3b; Group 4, CKD stage 4; Group 5, CKD stage 5; and Group 6, CKD stage 3b and heart failure. For all patients, plasma concentrations of copeptin, creatinine, urea, cystatin C, sodium, C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and blood pH were assessed. We found that plasma content of creatinine, urea, CRP, cystatin, NT-proBNP, and copeptin increased with CKD progression. Heart failure in CKD patients was not the cause of an appreciable increase of copeptin level. Copeptin/creatinine, copeptin/cystatin C ratios, and especially copeptin/eGFR ratio enhanced copeptin prognostic sensitivity concerning renal failure in CKD, compared with copeptin alone. The copeptin×NT-proBNP ratio decreased along CKD progression, reaching a nadir in the accompanying heart failure. In contradistinction, copeptin×NT-proBNP/creatinine ratio increased along CKD progression, reaching a peak in the accompanying heart failure. We conclude that copeptin is an important marker in CKD, but not so concerning heart failure in the disease. A decrease in copeptin×NT-proBNP and an increase in copeptin×NT-proBNP/creatinine ratio are useful markers of cardiac function decline in CKD.

Topics: Adult; Aged; Biomarkers; Creatinine; Disease Progression; Glomerular Filtration Rate; Glycopeptides; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic

The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF.. We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002).. Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Comorbidity; Female; Geriatric Assessment; Heart Failure; Hospital Mortality; Humans; Italy; Leukocyte Count; Male; Malnutrition; Natriuretic Peptide, Brain; Nutrition Assessment; Nutritional Status; Patient Admission; Patient Readmission; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Time Factors

Echocardiography is the most valuable tool for assessing cardiac abnormalities of chronic kidney disease (CKD) patients even though it has its limitations, including high equipment cost and the need for specialized personnel. Assessment of volume status is important not only for volume management, but also for prevention of cardiovascular disease of the CKD patients. Recently, bioimpedance is gaining acceptance as a way to quantitatively assess patient hydration status at bedside.. 127 patients who were admitted for planning their first dialysis treatment were enrolled. The echocardiography and bioimpedance spectroscopy (BIS) were performed. The association between echocardiographic data and clinical values such as NT-proBNP and OH/ECW was examined.. OH/ECW, which indicates relative fluid overload, was positively associated with LA dimension (r = 0.25, P = 0.007), LAVI (r = 0.32, P < 0.001), and E/e´ ratio (r = 0.38, P < 0.001). While OH/ECW was not significantly associated with echocardiographic values such as LVEDD, LVEDV, LVMI, and LVEF, NT-proBNP were significantly associated with all echocardiographic parameters. Multivariate logistic regression analysis showed E/e´ ratio (odds ratio, 1.14 [95% confidence interval (CI), 1.01 to 1.29]; P = 0.031), NT-proBNP (odds ratio, 4.78 [95% CI, 1.51 to 15.11]; P = 0.008), and albumin (odds ratio, 0.22 [95% CI, 0.08 to 0.66]; P = 0.007) were significantly associated with OH/ECW.. Since OH/ECW measured by BIS is associated with echocardiographic parameters related to diastolic dysfunction, preliminary screening through laboratory findings, including serum albumin in conjunction with OH/ECW and NT-proBNP, may find patient with risk of diastolic dysfunction. Our study suggests that a timely detection of fluid overload in patients with CKD as well as their proper treatment may help reduce diastolic dysfunction. Further research may be needed to validate the consistency of this association across other stages of CKD.

Topics: Body Water; Echocardiography; Electric Impedance; Extracellular Space; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic; Water-Electrolyte Imbalance

Sarcopenia is frequently observed and associated with poor outcomes in patients with chronic kidney disease (CKD). A simple screening test for sarcopenia using age, grip strength, and calf circumference was recently developed. However, the clinical utility of this sarcopenia score in patients with CKD remains unclear.. We calculated the sarcopenia score of 265 patients with CKD and followed the patients for cardiovascular events. The endpoint of this study was the composite of cardiovascular hospitalization and total mortality. We divided all participants into high (n = 166) and low (n = 99) sarcopenia score groups using a simple scoring system. Patients in the high sarcopenia score group showed significantly higher plasma B-type natriuretic peptide (BNP) levels than those in the low sarcopenia score group (median: 103.1, interquartile range: 46.3-310.0 vs. 46.7, 18.0-91.8 pg/mL; p < 0.0001). The Kaplan-Meier curve revealed that the risk of cardiovascular events was significantly greater in the high sarcopenia score group (log-rank test: p < 0.0001), even after potential confounding factors were corrected using propensity score matching. Multivariate Cox hazard analysis identified a high sarcopenia score (hazard ratio: 3.04, 95% confidence interval: 1.45-6.38, p = 0.003) as an independent predictor of the primary endpoints. Furthermore, the combination of a high sarcopenia score and high BNP level identified patients with a significantly higher probability of future events (p < 0.0001).. This study demonstrates that this simple screening score for sarcopenia could be a useful tool for estimating the future adverse event risk in patients with CKD.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Follow-Up Studies; Forecasting; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors; Sarcopenia

Previous studies revealed the association between serum Nterminal pro-brain natriuretic peptide (NT-proBNP) level and chronic kidney diseases (CKD) in general population. However, little is known about the association between serum NT-proBNP level and incident CKD in patients with type 2 diabetes. Thus, we investigated the impact of serum NT-proBNP level on incident CKD in patients with type 2 diabetes.. We enrolled 211 type 2 diabetic patients without CKD in this cohort study. CKD was diagnosed as estimated glomerular filtration rate <60 ml/min/1.73 m2. We divided the patients into three groups according to the tertiles of serum NT-proBNP level. Univariates and multivariate hazard ratios (HRs) for the incident CKD were calculated by Cox regression analyses.. Over the median follow-up period of 7 years, 56 patients developed incident CKD. Log NTproBNP was positively associated with incident CKD (HR 3.70, 95%CI 1.72-8.18, p <0.001). Compared with the lowest level of serum NT-proBNP tertile (≤36 pg/mL), the highest level of serum NTproBNP tertile (≥84 pg/mL) showed increased risk of incident CKD after adjusting age, sex, body mass index, hemoglobin A1c, creatinine, smoking, usage of hypertension drug and urinary albumin excretion at baseline examination (adjusted HR2.37, 95% CI 1.09-5.48, p = 0.028).. Serum NT-proBNP level is an independent biomarker for incident CKD in patients with type 2 diabetes.

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Female; Humans; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Time Factors

Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear.. We developed a BNP reporter mouse and occasionally found that this promoter was activated specifically in the papillary tip of the kidneys, and its activation was not accompanied by BNP mRNA expression. No evidence was found to support the existence of BNP isoforms or other nucleotide expression apart from BNP and tdTomato. The pBNP-tdTomato-positive cells were interstitial cells and were not proliferative. Unexpectedly, both the expression and secretion of BNP increased in primary cultured neonatal cardiomyocytes after their treatment with an extract of the renal papillary tip. Intraperitoneal injection of the extract of the papillary tips reduced blood pressure from 210 mmHg to 165 mmHg, the decrease being accompanied by an increase in serum BNP and urinary cGMP production in stroke-prone spontaneously hypertensive (SHR-SP) rats. Furthermore the induction of BNP by the papillary extract from rats with heart failure due to myocardial infarction was increased in cardiomyocytes.. These results suggested that the papillary tip express a substance that can stimulate BNP production and secretion from cardiomyocytes.

Topics: Animals; Cardiovascular Diseases; Cyclic GMP; Humans; Kidney Medulla; Mice; Mice, Transgenic; Myocytes, Cardiac; Natriuretic Peptide, Brain; Primary Cell Culture; Rats; Renal Insufficiency, Chronic

Left ventricular hypertrophy is the most common organ damage in children with chronic kidney disease (CKD).. The aim of the study was to assess the usefulness of B-type natriuretic peptide (BNP) as a marker of heart injury in children with CKD.. We included 66 children (41 boys and 25 girls) aged 0.7 to 18.6 (median 11.6) years with CKD stage 1-5. The concentrations of urea, creatinine, cystatin C and BNP in blood serum were assessed, and the estimated glomerular filtration rate (eGFR) was calculated from the Schwartz and Filler formulas. Patients were divided into groups depending on the CKD stage [group 1: CKD stages 1 + 2 (GFR> 60 ml/min/1.73 m2), group 2: stage 3 (GFR = 30-59 ml/min/1.73 m2), group 3: CKD stage 4 (GFR 15-29 ml/min/ 1.73 m2), group 4 - stage 5 (dialyzed children)]. On the basis of echocardiography, the left ventricular mass (LVM) was calculated, which was indexed for height (left ventricular mass index, LVMI). Left ventricular hypertrophy (LVH) was diagnosed if the LVMI value was > 95th percentile for sex and age.. Depending on the CKD stage the median BNP concentrations for group 1, group 2, group 3, and group 4 were 2.5 pg/ml, 6.0 pg/ml, 9.3 pg/ml and 18.0 pg/ml, and the LVH prevalence 27.3%, 33.3%, 60.0% and 63.6% , respectively. Significant correlations between BNP concentration and LVH expressed by LVMI (R=0.256, p=0.038), creatinine (R=0.453, p<0.001), cystatin (R=0.494, p<0.001) and eGFR (R=-0.473, p<0.001) were found.. In children with chronic kidney disease, BNP is an indicator of heart failure correlating with renal function parameters and left ventricular mass index.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Creatinine; Cystatin C; Female; Humans; Hypertrophy, Left Ventricular; Infant; Male; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Young Adult

Fluid overload is one of the major characteristics and complications in patients with chronic kidney disease (CKD). N-terminal pro-brain natriuretic peptide (NT-proBNP) is related to fluid status and fluid distribution. The aim of this study is to investigate the interaction between NT-proBNP and fluid status in adverse clinical outcomes of late stages of CKD.. We enrolled 239 patients with CKD stages 4-5 from January 2011 to December 2011 and followed up until June 2017. Fluid status was presented as hydration status (HS) value measured by body composition monitor, while HS>7% was defined as fluid overload. Clinical outcomes included renal outcomes (commencing dialysis and estimated glomerular filtration rate decline>3 ml/min/1.73 m2/year), all-cause mortality and major adverse cardiovascular events (MACEs).. During a mean follow-up of 3.3±2.0 years, 129(54.7%) patients commenced dialysis, 88(37.3%) patients presented rapid renal function decline, and 48(20.3%) had MACEs or died. All patients were stratified by HS of 7% and the median of plasma NT-proBNP. The adjusted risks for commencing dialysis was significantly higher in patients with high plasma NT-proBNP and HS>7% compared to those with low plasma NT-proBNP and HS≦7%. There was a significant interaction between plasma NT-proBNP and HS in commencing dialysis (P-interaction = 0.047). Besides, patients with high plasma NT-proBNP and HS>7% had greater risks for MACEs or all-cause mortality than others with either high plasma NT-proBNP or HS>7%.. NT-proBNP and fluid overload might have a synergistic association of adverse clinical outcomes in patients with late stages of CKD.

Topics: Aged; Biomarkers; Body Composition; Cardiovascular Diseases; Dialysis; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic; Treatment Outcome

It is unclear whether asymptomatic elevation of brain natriuretic peptide (BNP) is associated with cardiovascular events (CVEs) or heart failure (HF) in predialysis chronic kidney disease (CKD) patients.. We measured BNP in 482 asymptomatic predialysis patients with CKD stages 2-5 at nephrology referral between August 2004 and October 2010, and followed them prospectively to investigate the prognostic significance of BNP using Cox models and receiver operating characteristic (ROC) analyses. The primary composite end point was the time to death or the first nonfatal CVEs. Secondary end points included CVEs including sudden death, HF and all-cause death.. The median age was 67 years (male, 67.4%; diabetic nephropathy, 33.4%), and estimated glomerular filtration rate was 20.1 mL/min/1.73 m2. The primary end point occurred in 92 patients. CVEs including sudden death, HF and all-cause death occurred in 66, 35, and 54 patients, respectively during a median follow-up period of 37.7 months. Multivariate analyses showed that BNP level was significantly associated with the primary end point (hazard ratio [HR] 1.241; 95% CI 1.020-1.511; p = 0.031), CVEs (HR 1.337; 95% CI 1.067-1.675; p = 0.012) and HF (HR 1.489; 95% CI 1.059-2.091; p = 0.022), but not associated with all-cause death (HR 1.081; 95% CI 0.829-1.410; p = 0.565). The ROC curves showed that the optimal predictive BNP levels for the primary end point, CVEs and HF were 92.5, 127.0, and 274.6 (pg/mL) respectively.. Asymptomatic elevation of BNP is strongly predictive for CVEs and HF, which might help to integrate cardio-renal risk stratification in predialysis CKD patients.

Topics: Aged; Asymptomatic Diseases; Biomarkers; Cardiovascular Diseases; Cause of Death; Echocardiography; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Referral and Consultation; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; ROC Curve

Increased concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in dogs with azotemia have been documented. Knowledge of mechanisms behind increased concentrations of cardiac biomarkers in dogs with azotemia is warranted for correct interpretation of test results.. The aim of the article was to investigate possible associations between plasma concentrations of cTnI and NT-proBNP, respectively, and patient characteristics, glomerular filtration rate (GFR), a plasma volume factor (PVF) derived from scintigraphic examination (PVf), systolic blood pressure (SBP), selected hematologic and biochemical variables, and echocardiographic measurements in dogs with stable chronic kidney disease (CKD) and in healthy dogs.. Fifty student-, staff-, and client-owned dogs were included. Twenty-three of the dogs were healthy and 27 were diagnosed with CKD.. In this cross-sectional observational study, dogs with a previous diagnosis of CKD and healthy control dogs were included. At inclusion, all dogs were characterized by physical examination, repeated blood pressure measurements, complete urinalysis, hematology and biochemistry panel, echocardiography, abdominal ultrasound examination of the entire urinary tract, and scintigraphic examination for measurement of GFR.. Plasma volume factor and PCV were independently associated with NT-proBNP (Radj2 = 0.42; P < .0001). Age, body weight (BW), and SBP were independently associated with cTnI (Radj2 = 0.50; P < .0001).. Neither NT-proBNP nor cTnI concentrations were independently associated with measured GFR. Thus, findings were not suggestive of passive accumulation of either marker, suggesting that increased circulating concentrations of cTnI and NT-proBNP can be interpreted similarly in dogs with stable CKD as in dogs without CKD.

Topics: Animals; Azotemia; Blood Pressure; Case-Control Studies; Cross-Sectional Studies; Dog Diseases; Dogs; Female; Glomerular Filtration Rate; Male; Natriuretic Peptide, Brain; Peptide Fragments; Plasma Volume; Renal Insufficiency, Chronic; Troponin I

The presence and severity of proteinuria is considered an important prognostic marker in patients with chronic kidney disease (CKD) and is associated with mortality and morbidity. Cathepsin L is highly expressed in the foot processes of podocytes in the kidney, which serves as an ultrafiltration barrier. Cathepsin L is also up-regulated in the setting of inflammation as a feature of CKD. Therefore, we postulated that proteinuria severity in CKD patients might correlate with increased serum levels of cathepsin L.. In this retrospective observational study, a total of 135 patients diagnosed with CKD, 31 renal transplant patients and 48 healthy controls were included. The demographic characteristics and clinical indicators were analyzed. Serum cathepsin L activity was significantly higher in patients with CKD than in renal transplant recipients and healthy controls (P < 0.01). Patients with severe proteinuria had a higher cathepsin L activity compared to those with moderate or mild proteinuria (P < 0.01). Serum cathepsin L activity positively associated with age, body mass index, nitrite level, neutrophil count, high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide, high-mobility group box-1 protein (HMGB1) and 24-h proteinuria. In the ROC analysis, the sensitivity of cathepsin L activity in diagnosis of moderate and heavy is 0.86 and the specificity is 0.73. Moreover, CKD patients with higher cathepsin L activity had a significantly higher hospital admission rate. The data also showed patients with statin administration present significantly lower cathepsin L activity (P < 0.01), hs-CRP (P < 0.01), HMGB1 (P < 0.01) and proteinuria (P < 0.01) compared to non-statin treatment group.. This study revealed that serum cathepsin L activity is significantly elevated in CKD patients and its level correlates with the severity of proteinuria as well as prognosis, suggesting that serum cathepsin L may serve as a potential biomarker for CKD. Further prospective study is needed to explore its clinical implications in the future.

Topics: Adult; Biomarkers; C-Reactive Protein; Cathepsin L; Cholesterol, LDL; Cross-Sectional Studies; Female; HMGB1 Protein; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Transplantation; Leukocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Neutrophils; Nitrites; Proteinuria; Renal Insufficiency, Chronic; Retrospective Studies; ROC Curve; Severity of Illness Index

In this prospective study, we aimed to assess the haemodynamic changes before and after haemodialysis (HD) in cardiac healthy subjects on chronic HD by imaging methods and endocrine markers of fluid balance.. Mid-regional pro-atrial natriuretic peptide (MR-proANP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), vasopressin (AVP) and copeptin (CT-proAVP), metanephrines and normetanephrines, renin and aldosterone, standard transthoracic echocardiography and diameter of vena cava inferior (VCID) were performed in 20 patients with end stage renal disease (CKD5D) before and after HD and were stratified in residual excretion (RE, less or more 0.5 l) and ultrafiltration rate (UF, less or more 2 l).. Copeptin was significantly higher in patients before HD. Copeptin was inversely correlated with haemodialysis treatment adequacy (KT/v), RE and UF, but was not significantly influenced by age, gender and body mass index (BMI). MR-proANP was significantly reduced by haemodialysis by 27% and was inversely correlated with KT/v, but there was a significant influence by UF, RE, age, gender and BMI. NT-proBNP was significantly higher in patients before HD and was not influenced by RE and UF. Renin, aldosterone, metanephrines and normetanephrines did not demonstrate significant differences. Echocardiographic parameters and VCID were significantly correlated with RE, UF and copeptin.. Modern biomarkers will provide cardiovascular risk assessment, but elimination (UF), RE and other factors may influence the serum concentrations, e.g. in patients with renal impairment. The interpretation will be limited by altered reference ranges, and will be restricted to individual courses combined with clinical and echocardiographic data.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Glycopeptides; Health Status; Humans; Male; Metanephrine; Middle Aged; Natriuretic Peptide, Brain; Normetanephrine; Peptide Fragments; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Renin; Vasopressins; Vena Cava, Inferior

Identifying the primary etiology of cardio-renal syndrome in a timely manner remains an ongoing challenge in nephrology. We hypothesized that hypertensive kidney damage can be distinguished from chronic glomerulonephritis at an early stage of chronic kidney disease (CKD) using ultrasound (US) Doppler sonography.. Fifty-six males (age 54 ± 15, BMI 28.3 ± 3.5 kg/m. HT-CKD patients had reduced proximal renal cortex perfusion as well as reduced total and proximal renal cortex arterial area. Proximal renal cortex arterial area ≤0.149 cm. Evidence of diminished arterial vascularity or perfusion of renal proximal cortex, both derived from US Doppler, could be helpful in differentiating hypertensive nephropathy from glomerulonephritis-related CKD.

Topics: Adult; Age Factors; Aged; Carotid Intima-Media Thickness; Echocardiography; Essential Hypertension; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney Cortex; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Circulation; Renal Insufficiency, Chronic; ROC Curve; Stroke Volume; Troponin I; Ultrasonography, Doppler, Color

The aim of this prospective study was to evaluate the association between serum magnesium (Mg) and mortality, in particular the cause-specific mortality of Mg and other risk factors in hemodialysis (HD) patients.. We studied a cohort of 185 HD patients receiving thrice-weekly HD treatment, on a dialysate Mg concentration of 0.5 mmol/L. We stratified 3 patient groups according to the level of Mg: lower (<1.1 mmol/L), intermediate-reference (1.1 to <1.3 mmol/L), and higher (Mg >1.3 mm/L).. During the 5-year follow-up, 60 patients died, with cardiovascular (CV) disease as the predominant cause (73.3%). Hazard ratio (HR) for all-cause and CV mortality were 2.55 and 2.67 in the lower versus intermediate Mg group, but there was no significant association between the higher and intermediate Mg group. Univariate Cox regression analysis showed that Mg <1.1 versus 1.1-1.30 mml/L with HR 2.34, was a significant univariate predictor for increased mortality in addition to the Hb <110 g/L, Alb <40 g/L, C-reactive protein (CRP) ≥10 mg/L and brain natriuretic peptide >1,200 pg/mL. However, in the multivariate analysis only CRP ≥10 mg/L with HR 3.89 was a significant predictor of mortality. Subgroup analyses showed that among patients with CRP >10 mg/L, HR for all-cause and CV mortality of the lower versus intermediate Mg group were 1.96 and 2.39, respectively, not reaching significance for the higher versus intermediate Mg group. Conversely, there was no association between Mg level and all-cause and CV mortality within these 3 groups among patients with CRP <10 mg/L.. Lower serum Mg level was significantly associated with an increased all-cause and cardiovascular mortality in HD patients, especially in inflamed patients.

Topics: Aged; C-Reactive Protein; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Magnesium; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors

To determine the plasma level of N-terminal brain natriuretic peptide precursor (NT-proBNP) in patients with chronic kidney disease (CKD) and its association with cardiac function.. A total of 567 CKD patients admitted to the hospital from January 2013 to December 2014 were divided into six groups according to their estimated glomerular filtration rate. Their plasma level of NT-proBNP, renal function, and cardiac function were determined.. NT-proBNP is affected by renal function, which can be used for diagnosing cardiac failure in patients with CKD.

Topics: Biomarkers; Glomerular Filtration Rate; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

Chronic fluid overload is common in patients with chronic kidney disease (CKD) and can with time lead to diastolic dysfunction and heart failure. We investigated whether markers of fluid status, such as NT-proBNP and bioimpedance spectroscopy (BIS), can predict echocardiographic findings of diastolic dysfunction in non-dialysis CKD5 patients.. BIS, echocardiography, and measurement of serum NT-proBNP were performed in patients with non-dialysis CKD stage 5 at a single study visit. E/e´ ratio reflect mean LV diastolic pressure and a ratio greater than 15 was used as a definition of diastolic dysfunction.. Eighty-four patients were analyzed. Forty-six patients (54.76%) had E/e´ ratio ≤15 and 38 patients (45.24%) had E/e´ > 15 (diastolic dysfunction). Patients with E/e´>15 had significantly higher serum NT-proBNP (14,650 pg/mL) than patients with to E/e´≤15 (4,271 pg/mL) and had more overhydration (OH), 5.1 liters compared to 2.4 liters. The cut-off values predicting diastolic dysfunction were found to be 2,797 pg/mL for NT-proBNP and 2.45 liters for OH.. Regular monitoring of fluid status by BIS and NT-proBNP can be used to find patient with risk of developing diastolic dysfunction. Treatments to correct fluid overload may reduce the risk of developing diastolic dysfunction and improve cardiovascular outcome in patients with CKD.

Topics: Blood Pressure; Dielectric Spectroscopy; Echocardiography; Heart Failure, Diastolic; Humans; Linear Models; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Retrospective Studies; Ventricular Dysfunction, Left

The volume state of dialysis patients is important in guiding the dialysis process. Volume overload in these patients is associated with inflammation. The objectives of the present study were to assess the body composition of patients on hemodialysis; to determine the concentrations of B-type natriuretic peptide (BNP) in plasma and evaluate the association of BNP concentrations with volume overload; to determine the concentrations of C-reactive protein (CRP), albumin and superoxide dismutase (SOD) activities as indicators of inflammatory or antioxidant processes. The study included 79 maintenance hemodialysis patients. Assessment of body compartments was carried out using a body composition monitor (BCM). After BCM measurements, blood samples were taken from the patients for laboratory tests. There were 40 (50.6%) volume-overloaded patients (relative overhydration >15%). These patients had a higher prevalence of arterial hypertension (P < 0.05), significantly higher concentrations of BNP (P = 0.01), lower body mass index (P < 0.05) and lower fat tissue index (P < 0.05). There was a positive correlation between plasma BNP and CRP concentrations (ρ = 0.231; P < 0.05), and a negative correlation between (log) BNP and albumin (r = -0.021; P < 0.05), as well as (log) CRP and albumin concentrations (r = -3; P < 0.01). SOD activity was positively correlated with albumin concentrations (r = 0.254; P < 0.05). The concentrations of BNP in this study were associated with volume overload and inflammatory markers. Patients with a higher albumin concentration had higher SOD activity.

Topics: Aged; Albumins; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Female; Humans; Hypertension; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Renal Insufficiency, Chronic; Superoxide Dismutase

Cardiovascular disease is the leading cause of morbidity and mortality in patients receiving hemodialysis. Systemic metabolic perturbation is one of the hallmark abnormalities in patients at high cardiovascular risk. We sought to determine the relationship between circulating ketone body and clinical outcomes in patients with prevalent hemodialysis.. We retrospectively assessed the relationship between serum β-hydroxybutyrate (βOHB), the most abundant ketone body in the circulation, and prognosis in 405 stable hemodialysis patients. During a mean follow-up of 3.2±0.9 years, there were 54 major adverse cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization attributed to heart failure) and 67 all-cause deaths. Major adverse cardiovascular events rates increased from 11.1 per 1000 person-years in the lowest βOHB quintile (<89 μmol/L) to 80.1 per 1000 person-years in the highest quintile (>409 μmol/L). After adjusting for demographic characteristics, coronary artery disease, and atrial fibrillation, the highest βOHB quintile was associated with increased risk of major adverse cardiovascular events compared with the lowest quintile (hazard ratio, 10.2; 95% confidence interval [3.35-44.0];. Increased serum βOHB levels were independently associated with cardiovascular events and all-cause death in patients receiving hemodialysis. These results highlight the need for future studies to understand the mechanisms underlying these observations.

Topics: 3-Hydroxybutyric Acid; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cause of Death; Chi-Square Distribution; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Up-Regulation

Volume overload, frequently clinically asymptomatic is considered as a causative factor limiting the effectiveness of antihypertensive therapy in haemodialysis (HD) patients. Therefore, the aim of this study was to assess plasma levels of N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) and a C-terminal portion of the precursor of vasopressin (CT-proAVP, copeptin), surrogate markers of volume overload in HD patients in relation to the number of antihypertensive drugs used in the hypertension treatment.. One hundred and fifty adult HD patients (92 males) were enrolled into this study. Clinical data concerning blood pressure (BP) measurements prior haemodialysis session and pharmacotherapy were collected from all patients. In addition to routine laboratory parameters, plasma levels of NT-proBNP and CT-proAVP were measured, and daily sodium and water consumption were estimated with a portion-size food frequency questionnaire.. Among 145 (96.7%) hypertensive HD patients, 131 were receiving antihypertensive medication. Despite antihypertensive therapy, 31.0% had inadequate BP control. Plasma concentration of NT-proBNP was associated with systolic (R=0.19; p=0.02) but not diastolic BP values and with the number of received antihypertensive drugs (R=0.21; p=0.01). The highest NT-proBNP values were observed in patients receiving 3 or more antihypertensive drugs. In contrast, no significant correlation was found between plasma CT-proAVP concentrations and BP values as well as and the number of antihypertensive drugs. Receiver operator curve analysis showed that NT-proBNP values over 13,184 pg/mL predicted the use of at least 3 antihypertensive drugs in maximal doses in the therapy of hypertension, similar analyses performed for CT-proAVP showed much less specificity.. 1. Increased levels of NT-proBNP seems to be a better biomarker of multidrug antihypertensive therapy requirement than CT-proAVP. 2. Whether estimation of NT-proBNP in these patients will be also better biomarker than copeptin in the prediction of cardiovascular complications related to hypertension needs further investigations.

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Cardiovascular Diseases; Female; Glycopeptides; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic

To identify the most significant factor influencing blood levels of cytokines in patients at high and very high cardiovascular risk.. A patient base from the "Management of chronic patients with multiple diseases" project was analyzed. 523 patients (mean age, 87±17.8) were included. Plasma samples were analyzed for concentrations of sodium, creatinine, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, and NT-proBNP. GFR was calculated using the CKD-EPI formula. Time-related CHF progression was assessed in one year; the time-related progression was considered an increase in CHF stage. Salt consumption was determined using the Charlton: SaltScreener questionnaire at the baseline visit and at one year. Low-salt diet containing 5 g of salt per day was recommended to all patients; 3.5 g of salt per day was recommended to patients with a documented diagnosis of CHF. Statistical analysis was performed using the Statistica 10.0 software.. 52.2 % of included patients consumed 6-10 g of salt per day; 43.4 % of patients consumed 10 g of salt or more per day; and only 4.4 % of patients consumed 5 g of salt or less per day. 21 % of included patients were at high risk of cardiovascular complications whereas for the vast majority of patients (79 %), the risk was stratified as very high. Two clusters of patients were formed based on the grade of hypertension, one-year CHF progression, and plasma levels of IL-6, -8, and -18. The one-year progression of CHF most significantly influenced the levels of IL-18, -8, and -6. The IL-6 level was correlated with the NT-proBNP level; an approximately similar degree of correlation was found for NT-proBNP and BP.. Therefore, the performed statistical analysis determined correlations between the following factors: IL-6 level, NTproBNP level, and one-year CHF progression.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Creatinine; Heart Failure; Humans; Hypertension; Interleukins; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Risk Factors

Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Blood Pressure; Carotid Intima-Media Thickness; Echocardiography; Female; Glomerular Filtration Rate; Humans; Hypertension; Japan; Kidney; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Renin; Renin-Angiotensin System; Sodium, Dietary

Additional risk stratification may provide more aggressive and focalized preventive treatment to high-risk hypertensive patients according to the Japanese hypertension guidelines. We prospectively investigated the predictive value of high-sensitivity troponin I (hsTnI), both independently and in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP), for incident heart failure (HF) in high-risk hypertensive patients with preserved left ventricular ejection fraction (LVEF). Baseline hsTnI and NT-proBNP levels and echocardiography data were obtained for 493 Japanese hypertensive outpatients (mean age, 68.5 years) with LVEF ≥ 50%, no symptomatic HF, and at least one of the following comorbidities: stage 3-4 chronic kidney disease, diabetes mellitus, and stable coronary artery disease. During a mean follow-up period of 86.1 months, 44 HF admissions occurred, including 31 for HF with preserved ejection fraction (HFpEF) and 13 for HF with reduced ejection fraction (HFrEF; LVEF <50%). Both hsTnI (p < 0.01) and NT-proBNP (p < 0.005) levels were significant independent predictors of HF admission. Furthermore, when the patients were stratified into 4 groups according to increased hsTnI (≥highest tertile value of 10.6 pg/ml) and/or increased NT-proBNP (≥highest tertile value of 239.7 pg/ml), the adjusted relative risks for patients with increased levels of both biomarkers versus neither biomarker were 13.5 for HF admission (p < 0.0001), 9.45 for HFpEF (p = 0.0009), and 23.2 for HFrEF (p = 0.003). Finally, the combined use of hsTnI and NT-proBNP enhanced the C-index (p < 0.05), net reclassification improvement (p = 0.0001), and integrated discrimination improvement (p < 0.05) to a greater extent than that of any single biomarker. The combination of hsTnI and NT-proBNP, which are individually independently predictive of HF admission, could improve predictions of incident HF in high-risk hypertensive patients but could not predict future HF phenotypes.

Topics: Aged; Aged, 80 and over; Biomarkers; Echocardiography, Doppler; Female; Heart Failure; Hospitalization; Humans; Hypertension; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Stroke Volume; Troponin I; Ventricular Function, Left

In dialysis patients, electrocardiogram (ECG) abnormalities are common. However, the associations between the T-wave of the lead aVR (aVRT) amplitude and cardiovascular (CV) events or total mortality are unknown. We performed a prospective, observational cohort study of prevalent hemodialysis patients (N = 474), followed for 4 years. Outcomes were composite CV events and all-cause mortality. Predictors were baseline aVRT and other ECG findings. ECG parameters were analyzed in three models: model 1, univariate; model 2, basic adjustments; and model 3, model 2 plus serum albumin, C-reactive protein level, and NT-proBNP. By Cox analysis, aVRT was best associated with both endpoints through model 1 to 3 compared to other ECG findings. Patients categorized according to aVRT amplitude showed a step-by-step increase in hazard ratios for both endpoints. The aVRT amplitude level was significantly associated with not only composite CV events but also with all-cause mortality in prevalent dialysis patients.

Topics: Aged; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Electrocardiography; Female; Humans; Male; Middle Aged; Models, Statistical; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Serum Albumin

Chronic kidney disease (CKD) is a cause of coronary artery calcification (CAC) and an independent predictor of major adverse cardiac and cerebrovascular events (MACCE). Cathepsin K (CatK) is a lysosomal cysteine protease which affects vascular calcification and glucose metabolism disorder. We investigated the relationships among CatK, CAC, diabetes mellitus (DM) and MACCE in CKD patients. 113 consecutive CKD patients were enrolled. Their CAC was evaluated by computed tomography. Their plasma CatK level was measured by ELISA. They were divided into two groups by CatK levels and followed up for up to 3 years. The impact of CatK was analyzed in all participants, diabetic patients and non-diabetic patients. Kaplan-Meier analysis demonstrated a significant higher incidence of MACCE in the high CatK group (P = 0.028). The CatK level was significantly higher in patients with MACCE compared to that in patients without MACCE (P = 0.034). Cox's model revealed the higher plasma CatK and BNP level as independent predictors of MACCE (P = 0.043 and P < 0.01, respectively). Only in non-diabetic patients, there was a significant correlation between CatK and CAC score, and high CatK group had a significant higher level of LDL-C and LDL-C/HDL-C ratio (P < 0.05 and P < 0.001, respectively) than low CatK group. And these lipid disorders were independent predictors of CatK elevation. In CKD patients, our results indicated an impact of higher CatK level on their MACCE. The significant association among the CatK level, CAC and MACCE was found in non-diabetic CKD patients.

Topics: Aged; Aged, 80 and over; Cathepsin K; Coronary Artery Disease; Diabetes Mellitus; Female; Humans; Japan; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Tomography, X-Ray Computed; Vascular Calcification

Besides regulating calcium-phosphate metabolism, fibroblast growth factor-23 (FGF23) and Klotho have been proposed to have other roles in heart and vasculature. For example, FGF23 has been associated with cardiac hypertrophy and reduced left ventricular ejection fraction among patients with chronic kidney disease and cardiovascular disorders. The purpose of the study was to investigate whether serum FGF23 and α-Klotho concentrations are associated with cardiac diastolic dysfunction and related parameters among cardiac patients with preserved left ventricular ejection fraction. The current study enrolled 269 patients (69 women, 200 men) who were admitted to our cardiology department between October 2012 and January 2014 and had a left ventricular ejection fraction of >50%. Cardiac diastolic function was assessed by blood flow and tissue Doppler velocities, plasma B-type natriuretic peptide (BNP) concentration, and cardiac hypertrophy. After adjusting for sex, and age, logistic regression analysis showed that log(α-Klotho), but not log(FGF23), was significantly associated with diastolic dysfunction. After further adjustment for renal function, blood hemoglobin, and serum albumin levels, the negative association between log(α-Klotho) and diastolic dysfunction retained statistical significance with an odds ratio of 0.50 (95% confidence interval 0.31-0.81, P = 0.005, per 1 standard deviation). Among patients with preserved LVEF, serum α-Klotho concentrations were negatively associated with diastolic dysfunction. Whether modulation of serum levels α-Klotho will ameliorate cardiac diastolic function among patients with this disorder awaits further investigation.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Echocardiography, Doppler; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Glucuronidase; Heart Failure; Humans; Japan; Klotho Proteins; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Stroke Volume; Ventricular Dysfunction, Left

Serum neutrophil gelatinase-associated lipocalin (NGAL) is recognized as a useful biomarker for acute kidney injury. Recently, elevated NGAL levels were reported in patients with heart failure and cardiac events, but the association between serum NGAL and severity of coronary artery disease (CAD) has not been investigated adequately. This study aimed to evaluate the association between serum NGAL concentration and CAD severity in patients without heart failure and chronic kidney disease. Two-hundred thirteen patients [mean age: 66.2 ± 9.2 (SD)] without heart failure and chronic kidney disease (estimated glomerular filtration rate >60 mL/min/1.73 m(2)) who underwent coronary angiography were retrospectively analyzed using the SYNTAX score. The mean concentration of serum NGAL was 134.3 ± 111.3 ng/mL. A statistically significant correlation was observed between serum NGAL levels and the SYNTAX score (R = 0.18, P = 0.0091). Multivariable analysis also showed elevated serum NGAL as an independent risk factor for a high SYNTAX score (P < 0.01). Moreover, we evaluated the association of serum NGAL and brain natriuretic peptide (BNP) with the SYNTAX score. Patients with high levels of serum NGAL (>100 ng/mL) and high levels of BNP (>25 pg/mL) had a higher SYNTAX score (low-low vs. high-high: 13.8 ± 13.4 vs. 20.8 ± 18.9, P < 0.05). Serum NGAL levels were positively and significantly associated with CAD severity, and the evaluation of both serum NGAL and BNP was useful for predicting CAD in patients without renal dysfunction and heart failure. Serum NGAL might be a biomarker for CAD severity.

Topics: Aged; Biomarkers; Coronary Angiography; Coronary Artery Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Japan; Lipocalin-2; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Regression Analysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Severity of Illness Index

The relationship between B-type natriuretic peptide (BNP) concentration and renal outcomes in patients with chronic kidney disease (CKD) remains unclear; therefore, it has not been determined whether BNP is related to renal outcomes, independent of cardiac parameters. This study was designed to clarify whether BNP concentration is associated with renal outcomes in CKD patients, independent of cardiac functional and structural alterations.. This prospective observational study included 372 consecutive patients with CKD. The renal endpoint was the composite of doubling of serum creatinine concentration and end-stage renal disease requiring dialysis. BNP concentrations were divided into quartiles. A Cox proportional hazards model was utilized to determine the risk factors for poor renal outcomes.. During a median follow-up of 23.1 months, the renal endpoint was observed in 124 patients, including 14, 18, 37 and 55 patients in the first through fourth BNP quartiles, respectively. After adjustment for covariates, including cardiac parameters such as left atrial diameter, left ventricular mass index, left ventricular ejection fraction, and left ventricular hypertrophy, the hazard ratios (HRs) for renal outcomes became progressively higher for the second [HR, 1.50; 95% confidence interval (CI), 0.70-3.30), third (HR, 2.29; 95% CI, 1.11-4.91), and fourth (HR, 4.29; 95% CI, 2.05-9.39) BNP quartiles when compared with the lowest BNP quartile.. Higher BNP levels were associated with adverse renal outcomes, independent of cardiac structure and function, suggesting that BNP may be a useful biomarker for exploring factors associated with kidney disease progression.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Renal Insufficiency, Chronic

Data about the use of positive inotropic agents in patients hospitalized with acute decompensated heart failure (ADHF) is limited.. The records of 8066 patients with ADHF who were hospitalized at Hamad Medical Corporation, Qatar from 1991 to 2013 were analyzed to explore demographics and clinical characteristics of the patients according to inotropic agents use.. Eight hundred fifty eight patients [10.6%, 95% CI (10 to 11.3%)] received intravenous inotropic support. Patients receiving inotropes were more likely to be female and have preserved ejection fraction when compared to those not receiving inotropic agents. Comorbidities associated with higher likelihood of receiving inotropic treatment included acute myocardial infarction, chronic renal impairment, dyslipidemia, hypertension, obesity and hyperglycemia. Patient on inotropes were more likely to undergone percutaneous coronary intervention (PCI), intra-aortic balloon pump support and intubation. There were no differences in the mean plasma BNP and CK-MB levels between the 2 groups. Heart failure patients receiving inotropes also were more likely to have complications including ventricular tachycardia (2.0% vs. 0.9%, p = 0.003), prolonged hospital stay (8.0 vs. 5.0 days, p = 0.001), cardiac arrest (14.6% vs. 3.2%, p = 0.001) and in-hospital mortality (30.8% vs. 9.1 %, p = 0.001). Over the study period there was an increase use of inotropic agents and decreased mortality rates.. Inotropic use increased over the period whereas; female gender and conventional cardiac risk factors were predictors of inotropic agents use in the study.

Topics: Acute Disease; Administration, Intravenous; Aged; Cardiotonic Agents; Comorbidity; Creatine Kinase, MB Form; Disease Progression; Dyslipidemias; Female; Heart Arrest; Heart Failure; Hospital Mortality; Hospitalization; Humans; Hyperglycemia; Hypertension; Intra-Aortic Balloon Pumping; Intubation, Intratracheal; Length of Stay; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Percutaneous Coronary Intervention; Population Growth; Qatar; Registries; Renal Insufficiency, Chronic; Respiration, Artificial; Retrospective Studies; Tachycardia, Ventricular

Women with chronic kidney disease (CKD) and chronic hypertension (CHT) frequently develop superimposed pre-eclampsia, but distinction from pre-existing disease is challenging. Plasma placental growth factor (PlGF), B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and serum relaxin concentrations were quantified in a longitudinal prospective cohort of 121 women with CKD: 44 with chronic hypertension, and 79 healthy controls. Biomarker concentrations were compared with 32 women with pre-eclampsia without pre-existing disease. Test performance was evaluated for diagnosis of superimposed pre-eclampsia requiring delivery within 14 days of sampling. PlGF was evaluated as a promising marker in a validation cohort of women with suspected pre-eclampsia (29 with CKD; 94 with chronic hypertension; 29 with superimposed pre-eclampsia requiring delivery within 14 days) and compared with women without pre-existing disease (290 with no pre-eclampsia and 176 with pre-eclampsia requiring delivery within 14 days). From 20 and up to 42 weeks of gestation, lower maternal PlGF concentrations had high diagnostic accuracy for superimposed pre-eclampsia requiring delivery within 14 days (receiver operator characteristic 0.85) and confirmed in the validation cohort. The other plasma and serum biomarkers were not discriminatory. Thus, plasma PlGF concentrations could potentially help guide clinical decision making regarding admission and delivery for superimposed pre-eclampsia.

Topics: Acute Kidney Injury; Adult; Biomarkers; Case-Control Studies; Female; Gestational Age; Humans; Hypertension; Lipocalin-2; Longitudinal Studies; Natriuretic Peptide, Brain; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Relaxin; Renal Insufficiency, Chronic

Objective To analyze the relationship between serum high-sensitivity cardiac troponin T (hs-cTnT) and cardiovascular disease (CVD) among non-dialysis chronic kidney disease (CKD) patients, and to further explore its value of evaluating and predicting CVD in this population. Methods Five hundred and fifty-seven non-dialysis CKD patients were involved in this cross-sectional study. The relationship between serum hs-cTnT and CVD was analyzed using comparison between groups and regression analysis, and its value on assessing cardiac structure and function was evaluated by ROC curves. Results Median level of hs-cTnT was 13 (7-29) ng/L, with 1.7% undetectable, 46.4% greater than 99th percentile of the general population. Multivariate analysis suggested that compared with the lowest quartile of hs-cTnT, the highest quartile was approximately six times as likely to develop into LVH (OR, 6.515; 95% CI, 3.478-12.206, p < 0.05) and 18 times as likely to progress to left ventricular diastolic dysfunction(OR, 18.741; 95% CI, 2.422-145.017, p < 0.05). And Ln cTnT level had a more modest association with LVEF (OR, -1.117; 95% CI, -5.839 to -0.594; p < 0.05). When evaluated as a screening test, the area under the curve of ROC curves for hs-cTnT was 0.718, 0.788 and 0.736, respectively (p < 0.05). With a specificity of 90% as a diagnostic criterion, the value of hs-cTnT to evaluate LVH, LVEF < 50%, left ventricular diastolic dysfunction increased across CKD stages, from CKD 1 stage to CKD 5 stage. Conclusions In CKD non-dialysis population, hs-cTnT and NT-proBNP were valuable for evaluating LVH, left ventricular systolic dysfunction and left ventricular diastolic dysfunction.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; China; Cross-Sectional Studies; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Reproducibility of Results; Risk Factors; ROC Curve; Stroke Volume; Troponin T; Ventricular Dysfunction, Left

Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value for patients with cardiovascular disease, chronic kidney disease, etc, the prognostic significance of NT-proBNP levels in the general population has not been established. The aim of this study was to evaluate the clinical significance of NT-proBNP in a community population.. This is a community-based prospective survey of residents from two communities in Beijing conducted for a routine health status checkup. Out of 1,860 individuals who were eligible for inclusion from 2007 to 2009, 1,499 completed a follow-up and were assessed for the prognostic value of NT-proBNP in 2013. A questionnaire was used for end point events. Anthropometry and blood pressure were measured. Plasma NT-proBNP, creatinine, lipids, and glucose were determined.. A total of 1,499 subjects with complete data were included in the analysis. Participants were divided into four groups according to baseline NT-proBNP levels (quartile 1, <19.8 pg/mL; quartile 2, 19.8-41.6 pg/mL; quartile 3, 41.7-81.8 pg/mL; quartile 4, ≥81.9 pg/mL). During a median 4.8-year follow-up period, the all-cause mortality rate rose from 0.8% in the lowest concentration NT-proBNP group (<19.8 pg/mL) to 7.8% in the highest NT-proBNP group (≥81.9 pg/mL; P<0.001). The incidence of major adverse cardiovascular events (MACEs) increased from 3.1% in the lowest NT-proBNP group to 18.9% in the highest group (P<0.001). Individuals in the highest NT-proBNP group (≥81.9 pg/mL) were associated with higher risk of all-cause death and MACEs compared with the lowest NT-proBNP group using Kaplan-Meier survival curves and the Cox proportional hazard model after adjusting for age, sex, and traditional risk factors.. The plasma NT-proBNP level is a strong and independent prognosis factor for all-cause death and MACEs in the community population. The NT-proBNP cut-point for the prognostic value remains to be further studied. NT-proBNP is a strong and independent prognostic factor for all-cause death and MACEs in individuals older than 65 years and MACEs in individuals younger than 65 years.

Topics: Aged; Aged, 80 and over; Beijing; Biomarkers; Blood Glucose; Cardiovascular Diseases; Creatinine; Female; Humans; Kaplan-Meier Estimate; Linear Models; Lipids; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; ROC Curve; Surveys and Questionnaires

To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers.. We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics.. Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [β-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%).. These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.

Topics: Aged; Alanine Transaminase; Aspartate Aminotransferases; beta 2-Microglobulin; Biomarkers; C-Reactive Protein; Cohort Studies; Coronary Disease; Creatinine; Cystatin C; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Female; Fructosamine; gamma-Glutamyltransferase; Glomerular Filtration Rate; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Self Report; Serum Albumin; Stroke; Troponin T

To investigate the incidence and risk factors of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD).. 86 patients (53% men, 47% women; mean age, 45±13 years) with nondiabetic CKD were examined. According to the magnitude of glomerular filtration rate (GFR) decrease, all the patients were divided into 3 groups: 1) 33 patients with a GFR of 89--45 ml/min; 2) 33 with a GFR of 44--15 ml/min; 3) 20 with a GFR of <15 ml/min who were treated with hemodialysis. A control group consisted of 20 individuals with preserved kidney function (a GFR of >90 ml/min). Physical examination and transthoracic echocardiography were performed in all the patients. The serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNT) and cystatin C were determined.. PH was detected in 21 (24.4%) of the 86 patients with CKD. As CKD progressed, its prevalence in Groups 1, 2, and 3 increased, amounting to 18.2, 24.2, and 35%, respectively. The most predictably significant risk factors for PH were hypertension (ρ=0.35; р=0.001) and kidney dysfunction (creatinine (ρ=0.23; р=0.02). Elevated pulmonary artery systolic pressure (PASP) correlated with right ventricular (RV) dimension index (ρ=0.45; р<0.0001), right atrial volume index (ρ=0.3; р=0.02), left atrial volume index (ρ=0.3; р=0.009), and left ventricular mass index (ρ=0.35; р=0.03). In all the patients with CKD in the presence of PH, the NT-proBNP level was significantly higher than in its absence: 37.43 (5.83; 59.84) and 8.54 (5.1; 20.43) fmol/ml, respectively (р=0.01). Positive correlations were found between the level of cystatin C and the presence of PH (ρ=0.32; р=0.003). Analysis of the ROC curve (AUC=0.718; р=0.03) in the predialysis-stage CKD groups (n=66) revealed that the cystatin C level of > 1045 ng/ml with a sensitivity of 71% and a specificity of 60% suggested that PH was present. Multivariate analysis showed that the factors correlating with the presence of PH were NT-proBNP (β=0.34; р=0.008) and RV dimension index (β=0.3; р=0.002).. EchoCG reveals PH in almost 25% of the patients with CKD, which occurs at its predialysis stage. Elevated PASP is associated with myocardial structural changes. Traditional risk factors (hypertension) and diminished kidney function affect the development of PH.. Цель исследования. Изучение частоты и факторов риска развития легочной гипертонии (ЛГ) у больных хронической болезнью почек (ХБП). Материалы и методы. Обследовали 86 больных ХБП недиабетической этиологии (53% мужчин, 47% женщин, средний возраст 45±13 лет). В зависимости от степени снижения скорости клубочковой фильтрации (СКФ) всех больных разделили на 3 группы. В 1-ю группу включили 33 пациентов с СКФ 89-45 мл/мин, во 2-ю группу - 33 больных с СКФ 44-15 мл/мин, в 3-ю группу - 20 больных со СКФ <15 мл/мин, получающих лечение гемодиализом. Контрольную группу составили 20 лиц с сохранной функцией почек (СКФ >90 мл/мин). Всем проведено общеклиническое обследование и трансторакальная эхокардиография. Определяли концентрацию N-концевого предшественника натрийуретического пептида (NT-proBNP) и цистатина С в сыворотке крови. Результаты. ЛГ выявлена у 21 (24,4%) из 86 пациентов с ХБП. По мере прогрессирования ХБП ее распространенность в 1, 2 и 3-й группах нарастала, составляя 18,2, 24,2 и 35% соответственно. Наиболее прогностически значимыми факторами развития ЛГ были артериальная гипертония - АГ (ρ=0,35; р=0,001) и нарушение функции почек (креатинин ρ=0,23; р=0,02). Повышение систолического давления в легочной артерии (СДЛА) коррелировало с индексом размера правого желудочка - ПЖ (ρ=0,45; р<0,0001), индексом объема правого предсердия (ρ=0,3; р=0,02), индексом объема левого предсердия (ρ=0,3; р=0,009), индексом массы миокарда левого желудочка (ρ=0,35; р=0,03). У всех пациентов с ХБП при ЛГ уровень NT-proBNP был достоверно выше, чем в ее отсутствие, - 37,43 (5,83; 59,84) и 8,54 (5,1; 20,43) фмоль/мл соответственно (р=0,01). Обнаружены положительные корреляции между уровнем цистатина С и наличием ЛГ (ρ=0,32; р=0,003). При анализе ROС-кривой (AUC=0,718; р=0,03) в группах с додиализными стадиями ХБП (n=66) уровень цистатина С >1045 нг/мл с чувствительностью 71% и специфичностью 60% свидетельствовал о наличии ЛГ. При многофакторном анализе факторами, коррелирующими с наличием ЛГ, были NT-proBNP (β=0,34; р=0,008) и индекс размера ПЖ (β=0,3; р=0,002). Заключение. По данным ЭхоКГ ЛГ выявляется почти у 25% больных ХБП, возникая на додиализной стадии. Повышение СДЛА сопряжено со структурными изменениями миокарда. На развитие ЛГ влияют традиционные факторы риска (АГ) и снижение функции почек.

Topics: Adult; Creatinine; Cystatin C; Echocardiography; Female; Glomerular Filtration Rate; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; ROC Curve

Both Framingham criteria and natriuretic peptides (NPs) may worsen their diagnostic validity for acute decompensated heart failure (ADHF) in elderly patients with comorbidities, mainly renal failure. Ultrasound of inferior vena cava (IVCu) and bioelectrical impedance analysis (BIA) are useful tools for detecting ADHF, although their utility compared with NP is not fully established.. We conducted a prospective study with 96 patients who presented at the emergency department with dyspnea and were classified as ADHF and non-ADHF groups. Inferior vena cava ultrasonography measured maximum and minimum inferior vena cava diameters and collapsibility index (CIx), whereas BIA calculated resistance (Rz) and reactance (Xc). The primary goal was to compare amino-terminal pro-B-type NP (NT-proBNP), IVCu, and BIA for identifying ADHF. The ADHF group showed significantly (P<.001) higher NT-proBNP values (5801 vs 599 pg/mL), higher maximum IVC diameter (2.26 vs 1.58 cm), higher minimum IVC diameter (1.67 vs 0,7 cm), and lower CIx (27% vs 59%), as well as lower Rz (458.8 vs 627.1 Ohm) and lower Xc (23.5 vs 38.4 Ohm) compared with the non-ADHF group. The estimated area under the curve for ADHF diagnosis was 0.84 for NT-proBNP, 0.90 for maximum IVC diameter, 0.93 for minimum IVC diameter, and 0.90 for CIx, as well as 0.83 and 0.80 for Rz and Xc respectively, without finding significant difference. Cutoff values for diagnosis of ADHF with IVCu and BIA are proposed. Amino-terminal pro-B-type NP values significantly varied in patients with renal impairment, independently of ADHF status, whereas neither IVCu nor BIA did.. Inferior vena cava ultrasonography and BIA analysis are as useful as NT-proBNP to ADHF diagnosis, validated in an elderly population with kidney disease.

Topics: Aged; Aged, 80 and over; Dyspnea; Electric Impedance; Emergency Service, Hospital; Female; Heart Failure; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Ultrasonography; Vena Cava, Inferior

The evaluation of prognosis and determination of a long-term treatment strategy is an important element of management in patients with heart failure (HF).. The aim of the study was to determine the prognostic value of the Model for End-Stage Liver Disease (MELD) and its modifications, MELD and serum sodium (MELD-Na) and MELD excluding the international normalized ratio (MELD-XI), as well as other independent risk factors for death during a 4-year follow-up. We analyzed retrospectively 143 patients with advanced HF, evaluated for heart transplant between 2009 and 2011. Patients using warfarin were excluded from the study. The long-term follow-up data were obtained during follow-up visits and/or phone contact with the patients or their families.. The age of the patients was 54 (48-59) years and 88.1% of patients were male. Mortality rate during the follow-up period was 49%. The MELD scores (hazard ratio [HR], 1.12; P < .001), as well as serum high-sensitivity C-reactive protein (hs-CRP; HR, 1.01; P < .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; HR, 1.01; P < .05) levels, were independent risk factors for death. Receiver operator characteristic analysis indicated that a MELD cutoff of 10 (area under the curve [AUC], 0.756; P < .0001], MELD-XI cutoff of 13.0 (AUC, 0.720; P < .0001), MELD-Na cutoff of 13.0 (AUC, 0.813; P < .0001), hs-CRP cutoff of 4.02 (AUC, 0.686; P < .001), and NT-proBNP cutoff of 1055 (AUC, 0.722; P < .001) were the best predictive values as predictors of death.. MELD, MELD-Na, and MELD-XI scores are prognostic factors for death during a 4-year follow-up. A high MELD score is an independent prognostic factor for death. NT-proBNP and hs-CRP serum concentrations are other independent factors influencing death.

Topics: Biomarkers; C-Reactive Protein; End Stage Liver Disease; Epidemiologic Methods; Female; Heart Failure; Heart Transplantation; Humans; International Normalized Ratio; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic

Natriuretic peptides and echocardiographic parameters both predict cardiovascular events in patients with CKD. However, it is unknown whether simultaneous assessment of amino-terminal probrain natriuretic peptide (NT-proBNP) and echocardiographic parameters provides complementary or redundant predictive information; in the latter case, one of these two might be dispensable. We aimed to analyze the implications of using NT-proBNP alone, echocardiographic parameters alone, or a combination of both for prediction of adverse cardiovascular outcome.. Within the longitudinal Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Fourth Homburg Evaluation Study, we prospectively studied 496 patients with CKD stages G2-G4, in whom we measured NT-proBNP. Left ventricular mass index, left atrial volume index, diastolic left ventricular function, and systolic left ventricular function were assessed echocardiographically. During 4.5±2.0 years of follow-up, the occurrence of (1) decompensated heart failure or all-cause mortality and (2) atherosclerotic events or all-cause mortality was recorded. We assessed the association of NT-proBNP and echocardiographic parameters with outcome (using Cox models) and evaluated the increased discriminative value associated with the addition of echocardiographic parameters and NT-proBNP (using integrated discrimination improvement and net reclassification improvement).. During follow-up, 104 patients suffered decompensated heart failure or all-cause mortality, and 127 patents had atherosclerotic events or all-cause mortality. In univariable analyses, NT-proBNP and echocardiographic parameters predicted cardiovascular events. NT-proBNP remained an independent predictor for both end points in multivariate analysis, whereas left ventricular mass index, left atrial volume index, and diastolic left ventricular function did not. The addition of NT-proBNP on top of clinical and various echocardiographic variables was associated with improvements in reclassification for decompensated heart failure or all-cause mortality (integrated discrimination improvement =6.5%-8.3%; net reclassification improvement =23.1%-27.0%; all P≤0.03). Adding echocardiographic variables on top of clinical variables and NT-proBNP was not associated with significant net reclassification improvement (all P>0.05).. Our data confirm NT-proBNP is an independent predictor of adverse outcomes in patients with CKD. The additional use of echocardiography for improvement of risk stratification is not supported by our results.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Cerebral Revascularization; Echocardiography; Female; Heart Atria; Heart Failure; Humans; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Severity of Illness Index; Stroke; Ventricular Dysfunction, Left

Anticipating the time to renal replacement therapy (RRT) in chronic kidney disease (CKD) patients is an important but challenging issue. Natriuretic peptides are biomarkers of ventricular dysfunction related to poor outcome in CKD. We comparatively investigated the value of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as prognostic markers for the risk of RRT in stage 4 and 5 CKD patients, and in foretelling all-cause mortality and major cardiovascular events within a 5-year follow-up period.. Baseline plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche) were measured at inclusion. Forty-three patients were followed-up during 5 years. Kaplan-Meier analysis, with log-rank testing and hazard ratios (HR), were calculated to evaluate survival without RRT, cardiovascular events or mortality. The independent prognostic value of the biomarkers was estimated in separate Cox multivariate analysis, including estimated glomerular filtration rate (eGFR), creatininemia and comorbidities.. During the first 12-month follow-up period, 16 patients started RRT. NT-proBNP concentration was higher in patients who reached endpoint (3221 ng/L vs 777 ng/L, p = 0.02). NT-proBNP concentration > 1345 ng/L proved significant predictive value on survival analysis for cardiovascular events (p = 0.04) and dialysis within 60 months follow-up (p = 0.008). BNP concentration > 140 ng/L was an independent predictor of RRT after 12 months follow-up (p<0.005), and of significant predictive value for initiation of dialysis within 60 months follow-up.. Our results indicate a prognostic value for BNP and NT-proBNP in predicting RRT in stage 4 and 5 CKD patients, regarding both short- and long-term periods. NT-proBNP also proved a value in predicting cardiovascular events. Natriuretic peptides could be useful predictive biomarkers for therapeutic guidance in CKD.

Topics: Aged; Biomarkers; Cohort Studies; Disease Progression; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Renal Dialysis; Renal Insufficiency, Chronic; Severity of Illness Index

Hepcidin regulates systemic iron homeostasis by downregulating the iron exporter ferroportin. Circulating hepcidin is mainly derived from the liver but hepcidin is also produced in the heart. We studied the differential and local regulation of hepcidin gene expression in response to myocardial infarction (MI) and/or chronic kidney disease (CKD). We hypothesized that cardiac hepcidin gene expression is induced by and regulated to severity of cardiac injury, either through direct (MI) or remote (CKD) stimuli, as well as through increased local iron content.. Nine weeks after subtotal nephrectomy (SNX) or sham surgery (CON), rats were subjected to coronary ligation (CL) or sham surgery to realize 4 groups: CON, SNX, CL and SNX + CL. In week 16, the gene expression of hepcidin, iron and damage markers in cardiac and liver tissues was assessed by quantitative polymerase chain reaction and ferritin protein expression was studied by immunohistochemistry.. Cardiac hepcidin messenger RNA (mRNA) expression was increased 2-fold in CL (p = 0.03) and 3-fold in SNX (p = 0.01). Cardiac ferritin staining was not different among groups. Cardiac hepcidin mRNA expression correlated with mRNA expression levels of brain natriuretic peptide (β = 0.734, p < 0.001) and connective tissue growth factor (β = 0.431, p = 0.02). In contrast, liver hepcidin expression was unaffected by SNX and CL alone, while it had decreased 50% in SNX + CL (p < 0.05). Hepatic ferritin immunostaining was not different among groups.. Our data indicate differences in hepcidin regulation in liver and heart and suggest a role for injury rather than iron as the driving force for cardiac hepcidin expression in renocardiac failure.

Topics: Animals; Bone Morphogenetic Protein 6; Cation Transport Proteins; CCAAT-Enhancer-Binding Protein-alpha; Connective Tissue Growth Factor; Cytokines; Gene Expression Regulation; Heme Oxygenase (Decyclizing); Hepcidins; Iron; Liver; Male; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Rats, Inbred Lew; Renal Insufficiency, Chronic

Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p < 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m2. We divided patients into four subgroups (group 1, L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

Topics: Aged; Albuminuria; Arrhythmias, Cardiac; Biomarkers; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Electrocardiography; Fatty Acid-Binding Proteins; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors; Troponin T

High-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strongly predict heart failure (HF) in the general population. However, the interpretation of levels of these biomarkers as predictors of HF is uncertain among patients with CKD. Here, we investigated whether hsTnT and NT-proBNP are associated with incident HF among patients with CKD. In a prospective cohort analysis, we studied 3483 people with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study recruited from June of 2003 to August of 2008 who were free of HF at baseline. We used Cox regression to examine the association of baseline levels of hsTnT and NT-proBNP with incident HF after adjustment for demographic factors, traditional cardiovascular risk factors, markers of kidney disease, pertinent medication use, and mineral metabolism markers. At baseline, hsTnT levels ranged from ≤5.0 to 738.7 pg/ml, and NT-proBNP levels ranged from ≤5 to 35,000 pg/ml. Compared with those who had undetectable hsTnT, participants in the highest quartile (>26.5 pg/ml) had a significantly higher rate of HF (hazard ratio, 4.77; 95% confidence interval, 2.49 to 9.14). Similarly, compared with those in the lowest NT-proBNP quintile (<47.6 pg/ml), participants in the highest quintile (>433.0 pg/ml) experienced a substantially higher rate of HF (hazard ratio, 9.57; 95% confidence interval, 4.40 to 20.83) [corrected]. In conclusion, hsTnT and NT-proBNP were strongly associated with incident HF among a diverse cohort of individuals with mild to severe CKD. Elevations in these biomarkers may indicate subclinical changes in volume and myocardial stress that subsequently contribute to clinical HF.

Topics: Adult; Aged; Biomarkers; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Troponin T

Patients with chronic kidney disease (CKD) present a markedly increased cardiovascular (CV) morbidity and mortality since the early stages and have a high prevalence of accelerated atherosclerosis, inflammation and endothelial dysfunction. Nontraditional cardiovascular risk factors and serum cardiac biomarkers would contribute to explain this increased morbidity.. The aim is to investigate the relation among serum cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), nontraditional cardiovascular risk factors (serum uric acid, homocysteine), inflammatory indexes (C-reactive protein (CRP) serum ferritin, fibrinogen) and noninvasive predictors of atherosclerosis (carotid intima-media thickness (cIMT), brachial artery flow mediated dilation (baFMD), and left ventricular mass index (LVMI)) in CKD patients.. In 50 patients with CKD in stage 2/3 kidney disease outcomes quality initiative (KDOQI) and 18 age- and sex-matched healthy controls, the following parameters were measured: cardiac markers (cTnT and NT-proBNP), renal function, inflammatory markers (CRP, serum ferritin and fibrinogen), serum uric acid and homocysteine. We have also evaluated LVMIs, cIMT and baFMD.. In our study, we showed an increase of NT-proBNP and the serum cTnT, of serum uric acid and homocysteine with a positive correlation with the increase of cIMT and LVMI and reduced baFMD compared with the controls.. Serum cardiac biomarkers and nontraditional cardiovascular risk factors increase already in the stage 2/3 KDOQI contributing to explain the high cardiovascular morbidity and mortality of these patients. The NT-proBNP seems to have a rise earlier compared with serum cTnT; however, both seemed to be a useful clinical biomarker for evaluating noninvasive predictors of atherosclerosis in CKD patients.

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Endothelium, Vascular; Female; Humans; Inflammation; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Acuity; Peptide Fragments; Predictive Value of Tests; Prognosis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Troponin T; Ventricular Dysfunction, Left

Topics: Female; Glomerular Filtration Rate; Humans; Kidney; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Troponin T

Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.. N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.. In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).. Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.

Topics: Age Factors; Aged; Aging; Biomarkers; Cystatin C; Disease Progression; Female; Glomerular Filtration Rate; Humans; Incidence; Kidney; Linear Models; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Troponin T; United States; Up-Regulation

Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers.. To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers.. Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomarkers Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid-Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90mL/min/1.73m(2).. Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a GFR of 15mL/min/1.73m(2) varied from 2-fold to 15-fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured GFR and increased more at low GFR compared to hs-cTnI. For hFABP and NTproBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations).. The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Fatty Acid-Binding Proteins; Female; Glomerular Filtration Rate; Glycopeptides; Humans; Male; Medical Records; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency, Chronic; Troponin I; Troponin T

In patients with acute decompensated heart failure (ADHF), both natriuretic peptides and renal impairment predict adverse outcomes. Our aim was to evaluate the complementary prognosis role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on cystatin C (CysC) for glomerular filtration rate (GFR) estimation in ADHF patients.. Renal impairment assessed by CysC-based CKD-EPI equations and natriuretic peptides have complementary prognostic value in ADHF patients.. The study included 613 consecutive patients presenting with ADHF. At admission, plasma levels of NT-proBNP and CysC were determined. The GFR was estimated using CysC-based CKD-EPI equations. The primary endpoint was death from any cause and heart failure readmission.. During the median follow-up of 365 days (interquartile range, 227-441 days), 323 patients (0.65 %patient-year) died or were readmitted for heart failure. After multivariate adjustment, estimated GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL were independent predictors of adverse outcomes (P < 0.01). The combination of GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL was associated with the highest risk of adverse outcomes. Furthermore, reclassification analyses demonstrated that use of both NT-proBNP and CysC-based CKD-EPI equations resulted in improving the accuracy for adverse outcomes prediction.. In patients with ADHF, the combination of NT-proBNP with estimated GFR using CysC-based CKD-EPI equations better predicts outcomes than either parameter alone and adds valuable complementary prognosis information to other established risk factors.

Topics: Aged; Aged, 80 and over; Biomarkers; Chi-Square Distribution; Cystatin C; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kaplan-Meier Estimate; Kidney; Logistic Models; Male; Middle Aged; Models, Biological; Multivariate Analysis; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Spain; Time Factors

Cardiovascular complications are the main cause of morbidity and mortality in peritoneal dialysis (PD) patients. Left ventricular hypertrophy (LVH) is a major predictor of the development of cardiovascular events. This study aimed to identify risk factors that contribute to the development of LVH and to determine their cutoffs in patients on maintenance peritoneal dialysis.In this cross sectional study we evaluated the association of 23 variables including age, PD vintage, ultrafiltration, urine volume, residual renal function, mean daily SBP, mean daily DBP, fasting glucose, HbA1c, peritoneal glucose load index (PGLI), fluid overload (FO), plasma brain natriuretic peptide (BNP), plasma hsCRP and IL-6, serum albumin, white blood cell (WBC) count, hemoglobin, hematocrit, triglycerides, LDL-C (low density lipoprotein cholesterol), HDL-C (high density lipoprotein cholesterol), and PTH with LVH in 38 stable patients on maintenance PD ≥ 24 months.LVH was detected in 57.9% of patients. Logistic regression and receiver operating characteristics (ROC) analysis revealed that HbA1c, PGLI, FO, plasma BNP, hsCRP and IL-6 seem to be possible predictors of LVH. The cutoffs associated with the presence of LVH were: 7.5%, 3.2 g/kg/day, 1.7 L, 330 pg/mL, 7.5 mg/dL and 3.3 pg/mL for HbA1c, PGLI, FO, plasma BNP, hsCRP and IL-6, respectively (sensitivity 72.8 to 81.8% and specificity 75.0 to 93.8%).The results suggest that efforts should be made to reduce the peritoneal glucose load (PGL), to improve the hydration status, and to attenuate the inflammatory process in order to reduce the risk of the development of LVH among PD patients.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Cross-Sectional Studies; Female; Glycated Hemoglobin; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors

Placental growth factor (PlGF) contributes to atherogenesis through vascular inflammation and plaque destabilization. High levels of PlGF may be associated with mortality and cardiovascular disease, but the relationship between PlGF level and adverse outcomes in patients with CKD is unclear. We conducted a prospective cohort study of 1351 consecutive participants with CKD enrolled in the Novel Assessment of Risk management for Atherosclerotic diseases in CKD (NARA-CKD) study between April 1, 2004, and December 31, 2011. During a median follow-up of 3 years, 199 participants died and 383 had cardiovascular events, defined as atherosclerotic disease or heart failure requiring hospitalization. In adjusted analyses, mortality and cardiovascular risk increased in each successive quartile of serum PlGF level; hazard ratios (HRs) (95% confidence intervals [95% CIs]) for mortality and cardiovascular risk, respectively, were 1.59 (0.83 to 3.16) and 1.55 (0.92 to 2.66) for the second quartile, 2.97 (1.67 to 5.59) and 3.39 (2.20 to 5.41) for the third quartile, and 3.87 (2.24 to 7.08) and 8.42 (5.54 to 13.3) for the fourth quartile. The composite end point of mortality and cardiovascular events occurred during the study period in 76.4% of patients in both the highest PlGF quartile (≥19.6 pg/ml) and the lowest eGFR tertile (<30 ml/min per 1.73 m(2)). The association between PlGF and mortality or cardiovascular events was not attenuated when participants were stratified by age, sex, traditional risk factors, and eGFR. These data suggest elevated PlGF is an independent risk factor for all-cause mortality and cardiovascular events in patients with CKD.

Topics: Aged; Atherosclerosis; Cardiovascular Diseases; Cohort Studies; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Placenta Growth Factor; Pregnancy Proteins; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Vascular Endothelial Growth Factor A

The aim of the present article was to evaluate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with contrast-induced nephropathy (CIN) and long-term outcomes in patients with chronic kidney disease (CKD) and relative preserved left ventricular function (LVF) undergoing percutaneous coronary intervention (PCI). We prospectively enrolled 1203 consecutive patients with CKD and preserved LVF undergoing elective PCI. The primary end point was the development of CIN, defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dL, from baseline within 48 to 72 hours after contrast medium exposure. CIN incidence varied from 2.2% to 5.2%. Univariate logistic analysis showed that lg-NT-pro-BNP was significantly associated with CIN (odds ratio [OR] = 3.93, 95% confidence interval [CI], 2.22-6.97, P < 0.001). Furthermore, lg-NT-pro-BNP remained a significant predictor of CIN (OR = 3.30, 95% CI, 1.57-6.93, P = 0.002), even after adjusting for potential confounding risk factors. These results were confirmed by using other CIN criteria, which were defined as elevations of the SCr by 25% or 0.5 and 0.3 mg/dL from the baseline. The best cutoff value of lg-NT-pro-BNP for detecting CIN was 2.73 pg/mL (537 pg/mL) with 73.1% sensitivity and 70.0% specificity according to the receiver operating characteristic (ROC) analysis (C statistic = 0.754, 95% CI, 0.67-0.84, P < 0.001). In addition, NT-pro-BNP ≥537 pg/mL (2.73 pg/mL, lg-NT-pro-BNP) was associated with an increased risk of all-cause mortality and composite end points during 2.5 years of follow-up. NT-pro-BNP ≥537 pg/mL is independently associated with an increased risk of CIN with different definitions and poor clinical outcomes in patients with CKD and relative preserved LVF undergoing PCI.

Topics: Age Factors; Aged; Biomarkers; Contrast Media; Female; Health Status; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; ROC Curve; Sex Factors; Ventricular Function, Left

Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF.. We studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (±SD) follow-up period of 4.3±1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4).. Symptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Chi-Square Distribution; Disease Progression; Female; Heart Failure; Hospitalization; Humans; Hypertrophy, Left Ventricular; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Contraction; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Surveys and Questionnaires; Time Factors; United States; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood.

Topics: Age of Onset; Animals; Compliance; Death, Sudden, Cardiac; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Gene Knockout Techniques; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Glomerulus; Long QT Syndrome; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Phenotype; Rats; Rats, Inbred Dahl; Recombinant Fusion Proteins; Renal Insufficiency, Chronic; Signal Transduction

We studied whether vasopeptidase inhibition corrects the structure and function of the small arteries in experimental chronic renal insufficiency (CRI).. After 5/6 nephrectomy (NX) surgery was performed on rats, there was a 14-week follow-up, allowing CRI to become established. Omapatrilat (40 mg/kg/day in chow) was then given for 8 weeks, and the small mesenteric arterial rings were investigated in vitro using wire and pressure myographs.. Plasma and ventricular B-type natriuretic peptide (BNP) concentrations were increased 2- to 2.7-fold, while systolic blood pressure (BP) increased by 32 mm Hg after NX. Omapatrilat treatment normalized the BNP and reduced the BP by 45 mm Hg in the NX rats. Endothelium-dependent vasorelaxation was impaired but the response to acetylcholine was normalized after omapatrilat treatment. Vasorelaxations induced by nitroprusside, isoprenaline and levcromakalim were enhanced after omapatrilat, and the responses were even more pronounced than in untreated sham-operated rats. Arterial wall thickness and wall-to-lumen ratio were increased after NX, whereas omapatrilat normalized these structural features and improved the strain-stress relationship in the small arteries; this suggests improved arterial elastic properties.. Omapatrilat treatment reduced BP, normalized volume overload, improved vasorelaxation and corrected the dimensions and passive elastic properties of the small arteries in the NX rats. Therefore, we consider vasopeptidase inhibition to be an effective treatment for CRI-induced changes in the small arteries.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Ventricles; Male; Mesenteric Arteries; Natriuretic Peptide, Brain; Nephrectomy; Pyridines; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Thiazepines; Vascular Remodeling; Vascular Stiffness; Vasodilation; Vasodilator Agents

Plasma levels of atrial and brain natriuretic peptides (ANP and BNP) are increased in patients with chronic kidney disease (CKD) complicated with deteriorated kidney function, but the relationship between the plasma level of ANP or BNP and the future development of CKD is unclear.. We measured the plasma ANP and BNP levels of 294 local residents without CKD in a Japanese community (56.5 ± 10.4 years, mean ± S.D.), who were followed up for the development of CKD over the next 7 years.. Sixty-three residents developed CKD during the follow-up period, and the baseline level of plasma ANP of these residents was significantly higher than in those without CKD development. Kaplan-Meier analysis showed that the residents with higher ANP than the median value developed CKD more frequently than those with lower ANP. The association between plasma ANP level and CKD development was found to be independent of baseline estimated glomerular filtration rate by a Cox proportional hazards model, while this association became insignificant when adjusted by age; plasma ANP was significantly correlated with age. Compared with ANP, the relationship between plasma BNP and CKD development was unclear in these analyses.. Age-related elevation of plasma ANP levels preceded the development of CKD in the general population of Japan, raising a possibility for ANP being involved in the development of CKD.

Topics: Adult; Age Factors; Aged; Atrial Natriuretic Factor; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors

The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2-year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non-diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Carotid Intima-Media Thickness; Follow-Up Studies; Humans; Interleukin-18; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Plaque, Atherosclerotic; Predictive Value of Tests; Renal Insufficiency, Chronic

B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful biomarkers in the management of heart failure. Both peptides are secreted into the circulation after cleavage of their precursor proBNP and excreted from the kidney in the active form or as metabolites. We investigated effects of kidney function on the levels and association of these peptides.. Plasma concentrations of BNP and serum concentrations of NT-proBNP were measured in 229 outpatients of our cardiology department (male/female = 138/91, mean age= 68 years) and 53 hospital outpatients on chronic haemodialysis (30/23, 68 years). Kidney function in nondialysed patients was assessed by estimated glomerular filtration rate (eGFR; mL/min/1.73 m(2)) and categorised across five stages. Effects of kidney function on BNP, NT-proBNP and their relationship were investigated.. Deterioration in kidney function increased BNP and NT-proBNP levels, as well as the NT-proBNP/BNP ratio, and these values were highest in patients on haemodialysis. The eGFR inversely correlated with BNP (r = -0.472), NT-proBNP (r = -0.579), and the NT-proBNP/BNP ratio (r = -0.454, all P < 0.0001). A significant correlation was observed between BNP and NT-proBNP at all stages of kidney function including patients on haemodialysis, but the correlation was significantly affected by kidney function.. Although circulating levels of both BNP and NT-proBNP increased with deteriorating kidney function, the impact of kidney function on NT-proBNP was much more pronounced than that on BNP. Kidney function should be taken into account when interpreting data on BNP, NT-proBNP and their relationship.

Topics: Aged; Aged, 80 and over; Biomarkers; Creatinine; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic

Determination of fluid overload is important in chronic kidney disease. Early diagnosis and treatment of volume overload may decrease morbidity and mortality. We aimed to determine body composition by using bioelectrical impedance analysis, and studying other clinical characteristics, inferior vena cava diameter, and N-terminal pro-B natriuretic peptide associated with hydration status in chronic kidney disease Stages 3&4 and 5 in patients not undergoing dialysis.. We examined 62 patients with Stages 3&4 and 68 patients with Stage 5 chronic kidney disease. Plasma NT-proBNP was measured and analyzed after log transformation. Inferior vena cave diameter was measured with echocardiography and indexed for body surface area. Hydration status was assessed using multi-frequency bioelectrical impedance analysis. Overhydration was defined as overhydration/extracellular water >0.15.. Overhydration was more frequent in Stage 5 than in Stages 3&4 patients. Systolic and diastolic blood pressure, inferior vena cava index, and log NT-proBNP were higher in overhydrated compared to non-overhydrated patients. A significant positive correlation existed between overhydration/extracellular water and log NT-proBNP, systolic and diastolic blood pressures, and inferior vena cava index. In multiple linear regression analysis, the variables associated with hydration status were male sex, extracellular water/total body water, and extracellular water/intracellular water (greater overhydration), while serum albumin levels had a negative association with overhydration.. Overhydration is more prevalent in Stage 5 chronic kidney disease patients than in Stages 3&4 patients. Bioelectrical impedance analysis, inferior vena cava diameter, and NT-proBNP analysis in chronic kidney disease are useful methods to determine the volume overload.

Topics: Adult; Aged; Blood Pressure; Body Composition; Echocardiography; Electric Impedance; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Serum Albumin; Vena Cava, Inferior; Water-Electrolyte Imbalance

The non-invasive differentiation of ischemic and non-ischemic acute heart failure (AHF) not resulting from acute myocardial infarction is difficult and has therapeutic and prognostic implications. The aim of this study was to assess whether plasma B-type natriuretic peptide (BNP) can identify ischemic etiology in patients with stage 4-5 chronic kidney disease (CKD) presenting with AHF.. We prospectively analyzed 61 patients. The diagnosis of ischemic AHF was confirmed by coronary angiography or stress myocardial perfusion imaging. Plasma levels of BNP were measured at admission (BNP1) and 48 h after admission (BNP2).. The mean age of the study patients was 67 years. In these patients, 70.5% had diabetes and 47.5% had dialysis-dependent CKD; 28 of these patients (45.9%) had an ischemic etiology with significantly higher concentrations of BNP1 and BNP2 than did patients without ischemia. The area under the receiver operating characteristic curve was 0.755 (P=0.001) for BNP1 and 0.868 (P<0.001) for BNP2 to detect ischemic etiology of AHF. Plasma BNP1 >2907 ng/L (odds ratio [OR], 10.9; 95% confidence interval [CI] 2.5-48.4; P=0.002) and BNP2 >2322 ng/L (OR 93.1, 95% CI 7.0-1238.7; P=0.001) were independently associated with an ischemic etiology of AHF.. Plasma BNP may represent a clinically useful non-invasive tool for identification of ischemic etiology of AHF in patients with stage 4-5 CKD.

Topics: Aged; Female; Heart Failure; Hospitalization; Humans; Male; Myocardial Ischemia; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Risk Factors; ROC Curve; Ultrasonography

Topics: Cardiovascular Diseases; Female; Humans; Kidney; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

Cardio-renal syndromes are characterized by the impairment of cardiac and renal functions. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL), and plasma B-type natriuretic peptide (BNP) are markers of acute kidney injury (AKI) and heart failure (HF), respectively.. GFR (99mTc-DTPA), plasma BNP, and plasma and urinary concentrations of NGAL were measured in 310 clinically stable CKD patients, at functional stages from 1 to 5. Serum and urinary low-molecular-weight proteins cystatin C and β2-microglobulin, and urinary tubular enzymes were measured for comparison. Plasma BNP, NGAL, cystatin C and β2-microglobulin were measured also in 31 maintenance hemodialysis patients.. Plasma NGAL increased with the reduction of GFR in CKD patients from stage 2. In the different CKD stages modest differences were found for BNP values. Urinary NGAL increased slightly but significantly in patients at CKD stages 4 and 5, similarly to urinary cystatin C and β2-microglobulin. In maintenance hemodialysis patients, plasma NGAL and BNP were markedly increased, and high-flux hemodialysis significantly decreased their plasma concentrations.. Plasma NGAL increases markedly with the reduction in GFR, generating a very high number of false positive diagnoses of AKI in stable CKD patients. The grade of GFR impairment and the cause of kidney disease have a lower effect on urinary NGAL and on plasma BNP. In any case, specific reference values of NGAL and BNP should be used in chronic kidney disease patients, according to their functional stage, when assessing acute kidney injury, heart failure, and cardio-renal syndromes in patients with impaired GFR.

Topics: Acute-Phase Proteins; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; False Positive Reactions; Female; Glomerular Filtration Rate; Heart Failure; Humans; Lipocalin-2; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Proto-Oncogene Proteins; Renal Insufficiency, Chronic; Young Adult

B-type natriuretic peptide (BNP) concentration predicts outcome in patients undergoing dialysis. Because survival and cardiovascular risk change across the CKD continuum, serial changes in BNP were compared in patients at different CKD stages and after kidney transplantation.. Patients with CKD stages 3 and 4 (CKD 3-4), dialysis patients, and kidney transplant recipients (KTRs) from one center had two measurements of BNP taken a median of 161 days apart in 2003-2004 and were followed until July 2012. Both BNP-32 (Triage BNP; Biosite Diagnostics) and NT-BNP-76 (proBNP; Roche Diagnostics) were assayed. The interaction between change in log-transformed BNP concentration over time and patient group was tested by fitting regression models on panel data with random effects. Survival after the second measurement was compared by tertile of change in BNP.. Patients with CKD 3-4 (n=48), dialysis patients (n=102), and KTRs (n=73) were followed for a median of 5.7, 4.8, and 5.9 years, respectively. The interaction between patient group and BNP measurements over time was significant for NT-BNP-76 (P<0.001) and BNP-32 (P<0.01). Median NT-BNP-76 increased in dialysis patients and those with CKD 3-4 from 3850 pg/ml (interquartile range [IQR], 1776-12,323 pg/ml) to 18,830 pg/ml (IQR, 6114-61,009 pg/ml; P<0.001) and from 698 pg/ml (IQR, 283-2922 pg/ml) to 2529 pg/ml (IQR, 347-9277 pg/ml; P=0.002), respectively. Change was not significant for KTRs or comparisons made with BNP-32. Survival rate was significantly lower for patients with the highest tertile of change in NT-BNP-76 among patients with CKD 3-4 (P=0.02), but not in the dialysis or KTR groups. In 11 patients who received a kidney transplant during the study, median NT-BNP-76 decreased from 9607 pg/ml (IQR, 2292-31,282 pg/ml) to 457 pg/ml (IQR, 203-863 pg/ml) after transplant (P<0.01).. The temporal trajectory of BNP differs between dialysis patients and those with CKD 3-4 and KTRs. This has important implications for the development of BNP-guided management strategies in CKD.

Topics: Adult; Aged; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic; Severity of Illness Index; Survival Rate; Time Factors

Topics: Cardiovascular Diseases; Female; Humans; Kidney; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that provides additional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluate its clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men). Patients were followed for 23 months (range, 13-32 months) for cardiovascular (CV) events and/or death. Strain patients (n = 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking, and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors of Strain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI. Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in 12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that of ECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients.

Topics: Aged; Antihypertensive Agents; C-Reactive Protein; Cardiovascular Diseases; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peripheral Vascular Diseases; Prognosis; Renal Insufficiency, Chronic; Smoking; Troponin

Traditional predictors suboptimally predict cardiovascular disease (CVD) in individuals with chronic kidney disease (CKD). This study compared 5 nontraditional cardiac and kidney markers on the improvement of cardiovascular prediction among those with CKD.. Among 8622 participants aged 52 to 75 years in the Atherosclerosis Risk in Communities (ARIC) Study, cardiac troponin T, N-terminal pro-B-type natriuretic peptide, cystatin C, β2-microglobulin, and β-trace protein were compared for improvement in predicting incident CVD after stratifying by CKD status (940 participants with CKD [kidney dysfunction or albuminuria]). During a median follow-up of 11.9 years, there were 1672 CVD events including coronary disease, stroke, and heart failure (336 cases in CKD). Every marker was independently associated with incident CVD in participants with and without CKD. The adjusted hazard ratios (per 1 SD) were larger for cardiac markers than for kidney markers, particularly in CKD (1.61 [95% confidence interval, 1.43-1.81] for cardiac troponin T, 1.50 [1.34-1.68] for N-terminal pro-B-type natriuretic peptide, and <1.26 for kidney markers). Particularly in CKD group, cardiac markers compared with kidney markers contributed to greater c-statistic increment (0.032-0.036 versus 0.012-0.015 from 0.679 with only conventional predictors in CKD and 0.008-0.011 versus 0.002-0.010 from 0.697 in non-CKD) and categorical net reclassification improvement (0.086-0.127 versus 0.020-0.066 in CKD and 0.057-0.077 versus 0.014-0.048 in non-CKD). The superiority of cardiac markers was largely consistent in individual CVD outcomes.. A greater improvement in cardiovascular prediction was observed for cardiac markers than for kidney markers in people with CKD. These results suggest that cardiac troponin T and N-terminal pro-B-type natriuretic peptide are useful for better CVD risk classification in this population.

Topics: Aged; beta 2-Microglobulin; Biomarkers; Cardiovascular Diseases; Cystatin C; Female; Humans; Incidence; Intramolecular Oxidoreductases; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Time Factors; Troponin T; United States

Biomarkers are useful tools for diagnosis and risk assessment of acute kidney injury and acute heart failure, particularly in ICU patients. Most biomarkers are produced or cleared by the kidney, so the presence of chronic kidney disease may affect their clinical reliability, particularly if the putative diagnosis of acute kidney injury or acute heart failure is based on a single measurement/single threshold approach. Better alternatives, such as establishing different diagnostic cutoff values per different chronic kidney disease strata or evaluating the diagnostic performance of a delta value (change from baseline levels) instead of a single threshold, should be carefully considered in critically ill patients with renal impairment and other co-morbidities.

Topics: Acute-Phase Proteins; Female; Glomerular Filtration Rate; Humans; Lipocalins; Male; Natriuretic Peptide, Brain; Proto-Oncogene Proteins; Renal Insufficiency, Chronic

Estimating fluid balance in haemodialysis patients is essential when determining dry weight, but limited methods are currently available. B-type natriuretic peptide (BNP) is a useful surrogate marker in patients with congestive heart failure (CHF), but whether its validity could be generalized to haemodialysis patients has not been studied well.. A total of 457 haemodialysis patients at a dialysis centre were analyzed. Determinants of BNP were assessed in connection with ultrasound cardiography (UCG) records, Kt/V, ultrafiltration rate (UFR), and demographic factors. All-cause death and cardiovascular (CV) events were recorded as the main outcome.. Among the UCG records, left atrial diameter (LAD), left ventricular ejection fraction (LVEF), were determinants of log-transformed (ln) BNP; UFR, age and sex were also significant. There was a positive correlation between BNP and LAD (r = 0.285, P < 0.001). Receiver operating characteristic (ROC) analysis revealed that BNP had 90% and 80% sensitivity to predict the presence of LA enlargement of 77.9 pg/mL and 133.2 pg/mL, respectively. Higher BNP and lower LVEF were associated with higher risk for developing all-cause death and CVD. In the adjusted model, patients with BNP higher than 471 pg/mL had hazard ratio of 2.18 (95% confidence interval (CI) 1.20-3.96, P = 0.01), compared to those with BNP <109 pg/mL.. B-type natriuretic peptide was determined by LAD, LVEF, UFR, age and sex. BNP and LAD had positive correlation and BNP could become a useful tool for estimating the presence of LA enlargement. BNP and LVEF was a strong risk factor for predicting all-cause death and CV events among patients undergoing haemodialysis.

Topics: Age Factors; Aged; Area Under Curve; Biomarkers; Cardiomegaly; Cause of Death; Female; Heart Atria; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; ROC Curve; Sex Factors; Stroke Volume; Treatment Outcome; Ultrasonography; Ventricular Function, Left; Water-Electrolyte Balance

Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart failure. Hypertension is a widely accepted risk factor for its outcome.. We analyzed 169 heart transplant recipients. The diagnosis of hypertension was made on the basis of information gathered at 3 consecutive visits. Complete blood count, urea, serum lipids, fasting glucose, creatinine, and N-terminal pro-B-type natriuretic peptide were also studied.. In the orthotopic heart transplantation (OHT) population, 11% had diabetes and 68% had chronic kidney disease. Hypertension was diagnosed and treated in 68% of the OHT patients. Hypertensive patients were significantly older, with a lower estimated glomerular filtration rate and higher serum creatinine and erythrocyte count. Thirty-three percent of patients did not achieve target blood pressure despite optimal medical treatment. Patients treated with tacrolimus had similar systolic blood pressure compared with those treated with cyclosporine (with a tendency to have lower values). Patients treated with mammalian target of rapamycin inhibitors had similar systolic and diastolic blood pressures compared with those treated without these inhibitors. In the group of patients given steroids, systolic and diastolic blood pressures were significantly lower than in the group not treated with steroids. In addition, steroid-treated patients had a significantly lower estimated glomerular filtration rate, hemoglobin, and erythrocyte count and higher serum creatinine, N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. Chronic kidney disease was also more prevalent in this group. Blood pressure was not related to the kidney function.. Despite polytherapy, optimal blood pressure control was not achieved in the majority of patients. OHT patients have a high prevalence of hypertension, which should be treated adequately. More efforts should be made to optimize blood pressure control, particularly when other comorbidities are present. Blood pressure was not related to patient kidney function.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Comorbidity; Creatinine; Cyclosporine; Erythrocyte Count; Female; Heart Transplantation; Humans; Hypertension; Immunosuppressive Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Tacrolimus

YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesions of atherosclerosis. Elevated serum YKL-40 levels are independently associated with the presence and extent of coronary artery disease and cardiovascular mortality. Because there are no data on heart transplant recipients and because they are prone to cardiovascular complications, the aim of this study was to assess YKL-40 in this population with particular attention to its relationship with endothelial damage. We studied 84 patients after heart transplantation. Healthy volunteers served as control subjects.. Complete blood count, urea, creatinine, lipids, fasting glucose, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and iron status were studied with the use of standard laboratory methods. We assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury von Willebrand factor (vWF) and midkine with the use of commercially available assays.. Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly higher in heart allograft recipients than in the control group (P < .001). In univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63 [P < .001]; estimated glomerular filtration rate, r = -0.44 [P < .001]), NT-proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation (r = 0.23; P < .05), copeptin (r = -0.42; P < .001), soluble transferrin receptor (r = 0.24; P < .05), hemoglobin (r = -0.42; P < .001), transferrin (r = -0.31; P < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001), ejection fraction (r = -0.28; P < .05), New York Heart Association functional class (r = -0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05), vWF (r = -0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate analysis, only creatinine was found to be a predictor of YKL-40 (β = 0.59; P = .02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients.. YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly owing to impaired renal function in patients after heart transplantation.

Topics: Adipokines; Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Chitinase-3-Like Protein 1; Coronary Disease; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Glycopeptides; Heart Transplantation; Humans; Inflammation; Interleukin-6; Lectins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Transplant Recipients

Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). We explored the relationship between CVD, plasma brain natriuretic peptide (BNP) and copeptin in non-dialysis patients with chronic kidney disease (CKD).. BNP and copeptin were measured using ELISA in 86 non-dialysis patients with different degrees of CKD and in 20 control patients. The effects of BNP, copeptin levels and other biochemical indices on carotid ultrasound echocardiography and CVD history were determined using correlation analysis.. BNP and copeptin levels were significantly higher in the CKD group than in the control group. Both indices increased progressively, in parallel with the decline in glomerular filtration rate (GFR). BNP levels were (184.25 ± 65.18) ng/L in early phase CKD, (975.245 ± 354.09) ng/L in middle phase CKD, and (1463.51 ± 614.92) ng/ml in end phase CKD compared with levels of (101.56 ± 42.76) ng/L in the control group (all P < 0.01). Copeptin levels in the middle phase ((20.36 ± 9.47) pmol/L) and end phase groups ((54.26 ± 18.23) pmol/L were significantly higher than in the control group ((9.21 ± 2.64) pmol/L; both P < 0.01). There was no difference in copeptin levels between early phase CKD ((10.09 ± 5.23) pmol/L) and control patients. Stepwise multiple regression analysis identified GFR, intima-media thickness (IMT), left ventricular hypertrophy (LVH), and previous history of CVD as independent risk factors for elevated BNP and copeptin levels.. BNP and copeptin appear to provide sensitive biological markers for the evaluation of atherosclerosis in non-dialysis patients with CKD.

Topics: Adult; Aged; Cardiovascular Diseases; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Glomerular Filtration Rate; Glycopeptides; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Young Adult

Topics: Acute Disease; Biomarkers; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic; Severity of Illness Index

Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations increase in dogs with azotemia. However, the correlation between glomerular filtration rate (GFR) and NT-proBNP concentrations in dogs has not been evaluated. The objective of this study was to evaluate the correlation between GFR and plasma NT-proBNP concentrations in dogs with chronic kidney disease (CKD). In this retrospective cross-sectional study, plasma creatinine (Cre) and NT-proBNP concentrations, plasma iohexol clearance (PCio) values and blood pressure were measured in dogs with CKD. Dogs were classified according to PCio values into D group (dogs with decreased PCio values), and N group (dogs with normal PCio values). Dogs were further categorized on the basis of their systolic blood pressure and PCio values into NT-D group (normotensive dogs with decreased PCio values), NT-N group (normotensive dogs with normal PCio values), HT-D group (hypertensive dogs with decreased PCio values) and HT-N group (hypertensive dogs with normal PCio values). Significant correlations were observed between plasma NT-proBNP and Cre concentrations (r=0.360, P<0.05) and PCio values (r=-0.470, P<0.01). Plasma NT-proBNP concentrations were significantly higher in the D group than in the N group (P<0.001). Plasma NT-proBNP concentrations were significantly higher in the HT-D group than in the other three groups (P ≤ 0.007). No differences in plasma NT-proBNP concentrations were observed between the NT-D and HT-N groups (P=0.28). Plasma NT-proBNP concentrations were significantly lower in the NT-N group than in the other three groups (P ≤ 0.043). Our findings suggest that decreased GFR might be associated with increased plasma NT-proBNP concentrations in dogs, similar to that in humans. In addition, the complication of hypertension in CKD might be associated with further increases in plasma NT-proBNP concentrations. In conclusion, the effects of GFR and blood pressure on the plasma NT-proBNP concentration were small, but it could be necessary to consider the effects when this marker is used to evaluate canine cardiac disease.

Topics: Animals; Dog Diseases; Dogs; Female; Glomerular Filtration Rate; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Retrospective Studies

Brain natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) are useful biomarkers for diagnosis and prediction of prognosis. Both of these peptides are elevated in patients with chronic kidney disease (CKD), but there is no evidence as to which peptide is the more suitable biomarker in patients with severe renal dysfunction.. This retrospective cohort study evaluated patients with cardiovascular diseases (64.9±11.7 years, mean±SD). The end points were all-cause death and a composite end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for severe heart failure, and initiation of hemodialysis. Baseline plasma BNP and NT-proBNP levels, expressed as log-transformed data, were closely correlated in patients with CKD stages 1-3 (n=998) (r2=0.870, p<0.001), whereas for CKD stages 4-5 (n=85) there was a significant but weaker correlation (r2=0.209, p<0.001). During follow-up periods (51.3±0.4 months), 132 patients died and 202 patients reached the composite end point. The area under the receiver operating characteristic curve (AUROC) for BNP and NT-proBNP were similar for CKD stages 1-3. However, for CKD stages 4-5, the AUC for mortality for BNP was 0.713 and that for NT-proBNP was 0.760, while the AUC for the composite end point for BNP was 0.666 and that for NT-proBNP was 0.720.. Both BNP and NT-proBNP are useful biomarkers for mortality and cardiovascular events, but NT-proBNP may be superior to BNP for CKD stages 4-5.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cohort Studies; Endpoint Determination; Female; Follow-Up Studies; Forecasting; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Renal Insufficiency, Chronic; Retrospective Studies; ROC Curve; Severity of Illness Index; Young Adult

The effect of impaired kidney function on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) is vague. This study was performed to examine the effect of kidney dysfunction on the afore-mentioned markers and determine appropriate cutoffs for systolic heart failure (SHF).. In this cross sectional study adults with estimated glomerular filtration rate (eGFR) <60 ml/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. SHF was defined as documented by a cardiologist with ejection fraction of < 40% and assessed by New York Heart Association classification (NYHA). Plasma was assayed for creatinine (Cr), BNP and NT-proBNP.. A total of 190 subjects were enrolled in the study, 95 with and 95 without SHF. The mean age of patients was 58 (±15) years, 67.4% being males. Mean BNP levels showed a 2.5 fold and 1.5 fold increase from chronic kidney disease (CKD) stage 3 to stage 5 in patients with and without SHF respectively. NT-proBNP levels in non-heart failure group were 3 fold higher in CKD stage 5 compared to stage 3. Mean NT-proBNP levels were 4 fold higher in CKD stage 5 compared to stage 3 in patients with SHF. Optimal BNP and NT-proBNP cutoffs of SHF diagnosis for the entire CKD group were 300 pg/ml and 4502 pg/ml respectively.. BNP and NT-proBNP were elevated in kidney dysfunction even in the absence of SHF; however the magnitude of increase in NT-proBNP was greater than that of BNP. BNP and NT-proBNP can be useful in diagnosing SHF, nonetheless, by using higher cutoffs stratified according to kidney dysfunction. NT-proBNP appears to predict heart failure better than BNP.

Topics: Adult; Aged; Biomarkers; Cross-Sectional Studies; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

The brain natriuretic peptides (BNP, NT-proBNP) are useful diagnostic markers of heart failure (HF), as exemplified by the ESC Heart Failure guidelines. The PolSenior project was an epidemiological study carried out to examine medical, psychological and socioeconomic aspects of aging in Poland. The aim of this study is an epidemiological description of HF based on elderly population from the PolSenior Study, stratified by NT-pro-BNP concentration values.. The research sample included 4979 respondents (2567 males and 2412 females) split into six equally sized age groups of elderly individuals. The study consisted of three visits performed by trained nurses and included a questionnaire survey, comprehensive geriatric assessment and blood and urine sampling with more than 50 biochemical parameters measured. Serum NT-pro-BNP was measured by electrochemiluminescence method (ECLIA).. The prevalence of chronic kidney disease (CKD) (77.8%) and atrial fibrillation (39.5%), number of hospitalizations (23.7%) and number of patients treated with HF drugs were highest in NT-proBNP > 2000 pg/ml group and least frequent in NT-proBNP < 400 pg/ml group. Obese patients had significantly more frequently NT-proBNP values < 400 pg/ml (73.0%) and less frequently NT-proBNP values >2000 pg/ml (2.8%). Age over 70 years and male gender were associated with the increased NT-pro-BNP (> 400 pg/ml) (OR 1.41; CI 1.20-1.65 for male gender).. We conclude that CKD and atrial fibrillation are associated with the occurrence of increased NT-pro-BNP, the surrogate for HF in elderly population. On the contrary, overweight or obesity is associated with lower prevalence of HF in elderly.

Topics: Aged; Aged, 80 and over; Aging; Antihypertensive Agents; Atrial Fibrillation; Biomarkers; Diabetes Mellitus; Drug Utilization; Female; Heart Failure; Hospitalization; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Poland; Prevalence; Renal Insufficiency, Chronic; Sex Characteristics

Achieving and maintaining optimal fluid status remains a major challenge in hemodialysis therapy. The aim of this interventional study was to assess the feasibility and clinical consequences of active fluid management guided by bioimpedance spectroscopy in chronic hemodialysis patients.. Fluid status was optimized prospectively in 55 chronic hemodialysis patients over 3 months (November 2011 to February 2012). Predialysis fluid overload was measured weekly using the Fresenius Body Composition Monitor. Time-averaged fluid overload was calculated as the average between pre- and postdialysis fluid overload. The study aimed to bring the time-averaged fluid overload of all patients into a target range of 0.5 ± 0.75 L within the first month and maintain optimal fluid status until study end. Postweight was adjusted weekly according to a predefined protocol.. Time-averaged fluid overload in the complete study cohort was 0.9 ± 1.6 L at baseline and 0.6 ± 1.1 L at study end. Time-averaged fluid overload decreased by -1.20 ± 1.32 L (P<0.01) in the fluid-overloaded group (n=17), remained unchanged in the normovolemic group (n=26, P=0.59), and increased by 0.59 ± 0.76 L (P=0.02) in the dehydrated group (n=12). Every 1 L change in fluid overload was accompanied by a 9.9 mmHg/L change in predialysis systolic BP (r=0.55, P<0.001). At study end, 76% of all patients were either on time-averaged fluid overload target or at least closer to target than at study start. The number of intradialytic symptoms did not change significantly in any of the subgroups.. Active fluid management guided by bioimpedance spectroscopy was associated with an improvement in overall fluid status and BP.

Topics: Aged; Blood Pressure; Blood Volume; Body Composition; Body Fluids; Body Weight; Dehydration; Dielectric Spectroscopy; Electric Impedance; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors

The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients.. We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1.. Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction.. NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Topics: Adult; Aged; Arginine; Biomarkers; Diastole; Female; Humans; Hypertension; Kidney Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

Children with chronic kidney disease (CKD) are at increased risk of future cardiovascular (CV) events. Our aim in this prospective single-centre cross-sectional analysis was to assess the relationship of a novel panel of CV biomarkers with left ventricular hypertrophy (LVH).. A panel of five CV biomarkers (asymmetric dimethyl arginine, high sensitivity C-reactive protein, homocysteine, N-terminal pro-B type natriuretic peptide and uric acid) were measured on the same day as an echocardiogram assessment, in paediatric patients with pre-dialysis stages 3-5 of CKD.. Of 73 children aged 5-18 years, LVH, all eccentric, was identified in 38%. Systolic blood pressure (BP), glomerular filtration rate (GFR) and higher intake of calcium-based phosphate binders were significantly worse in children with LVH. In multivariate models analysing each biomarker one at a time with confounders [GFR, systolic BP z-score, anti-hypertensive medication (yes/no) and elemental calcium intake], clinic systolic BP z-score and elemental calcium intake consistently displayed a significant relationship with indexed left ventricular mass (LVMI). None of the evaluated CV biomarkers displayed a significant relationship with LVMI.. In our cohort of children with moderately severe pre-dialysis CKD we have identified no suitable biomarkers to detect LVH. We would therefore recommend that echocardiographic determination of LVMI remains the technique of choice for detection of LVH in children with CKD.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Echocardiography; Female; Follow-Up Studies; Humans; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic

Impairment of kidney function is frequently observed in chronic heart failure (CHF). It correlates with clinical and neurohormonal status, and affects prognosis. We aimed to identify the prognostic impact of plasma renin activity (PRA) in patients affected by CHF with chronic kidney disease (CKD).. We enrolled 996 consecutive CHF patients (age 65 ± 13 years, mean ± SD, left ventricular ejection fraction, LVEF, 33 ± 10%), who underwent a complete clinical and neurohormonal characterization and were then followed-up (median 36 months) for the end point of cardiac death.. A stage ≥ 3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) was found in 437 patients. Impaired renal function was associated with worse symptoms, lower LVEF, higher plasma norepinephrine, NT-proBNP and PRA (all p<0.001). As compared to patients with preserved renal function, those with CKD had higher cardiac mortality [106 (24%) vs 53 (9.5%), p<0.001]. In CKD patients, at Cox multivariate analysis, only ejection fraction (HR 0.91, 95% CI 0.84-0.97, p=0.008), NT-proBNP (2.53, 1.45-4.41, p=0.001) and PRA (1.73, 1.16-2.58, p=0.007) were independent predictors of cardiac death. ROC analysis identified a cut-off value for PRA of 3.29 ng/mL/h that predicted prognosis with the greatest accuracy. Finally, the elevation of both NT-proBNP and PRA identified a subset of patients with the highest risk of cardiac death.. PRA has an independent prognostic value in CHF patients with CKD comorbidity. The combination of PRA and NT-proBNP identifies a group of high risk patients, who might benefit of a more intensive care, targeted to enhance renin-angiotensin system antagonism.

Topics: Aged; Aged, 80 and over; Biomarkers; Comorbidity; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Renin; Survival Rate

Serum indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). The aim of this study was to determine whether serum IS is associated with hemodynamic parameters or cardiac events in patients with nonischemic dilated cardiomyopathy (DCM).. The 76 patients with DCM had their serum IS and plasma brain natriuretic peptide (BNP) levels measured, and underwent echocardiographic examination. Mean (± standard deviation) left ventricular ejection fraction (LVEF) and BNP levels in the patients were 32.5 ± 10.7% and 204 ± 219 pg/ml, respectively. Patients were divided into 2 groups, low IS (<0.9 µg/ml) and high IS (≥ 0.9 µg/ml), based on the median value of serum IS. Although there were no significant differences in LVEF and BNP between the groups, E/e' was significantly greater in the high IS group than in the low IS group. Furthermore, E/e' was an independent determinant of serum IS level. The risk of a cardiac event was significantly higher in the high IS group than in the low IS group (P=0.014). Moreover, serum IS was a significant predictor of cardiac events even after adjustment for BNP.. Cardiac dysfunction is associated with the serum IS level, which might serve as a new prognostic marker in DCM patients with normal renal function or mild to moderate CKD.

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Dilated; Disease Progression; Female; Heart Failure; Humans; Indican; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renal Insufficiency, Chronic; Risk Factors; Stroke Volume; Ultrasonography; Uremia

The aim of the present study was to investigate the interaction of nutritional status, N-terminal probrain-type natriuretic peptide (NT-proBNP) and ventricular remodeling in hemodialysis patients.. NT-proBNP was measured by immunoassay. Nutritional status was assessed using the subjective global assessment (SGA) and malnutrition-inflammation score (MIS). Transthoracic echocardiographic examinations were performed on all patients.. 44 patients undergoing maintenance hemodialysis were enrolled in this study. Malnourished patients had higher levels of extracellular water (ECW) per kg body weight (BWt) than well-nourished patients and higher levels of NT-proBNP. MIS was positively correlated with left ventricular mass index (LVMI), log NT-proBNP and ECW/BWt, and negatively correlated with fat mass and LV systolic dysfunction. LV systolic dysfunction, LVMI and MIS were independently associated with log NT-proBNP levels. Multiple regression analysis showed that log NT-proBNP, mean arterial pressure and ECW/BWt were independently associated with LVMI. However, MIS did not have an independent relationship to LVMI.. Malnutrition in hemodialysis patients is accompanied by volume overload and associated with increased log NT-proBNP levels independent of volume status, and these levels are independently associated with increased LVMI. This suggests a possibility that nutritional status may affect ventricular remodeling in hemodialysis patients.

Topics: Adult; Aged; Biomarkers; Chi-Square Distribution; Cross-Sectional Studies; Echocardiography, Doppler; Female; Humans; Hypertrophy, Left Ventricular; Immunoassay; Linear Models; Male; Malnutrition; Middle Aged; Natriuretic Peptide, Brain; Nutrition Assessment; Nutritional Status; Peptide Fragments; Predictive Value of Tests; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease without clinical heart failure, the Chronic Renal Insufficiency Cohort (n = 3,232). The associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated using multivariate logistic and linear regression models. Reclassification of participants' predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement index that compared a clinical model with and without NT-proBNP. The median NT-proBNP was 126.6 pg/ml (interquartile range 55.5 to 303.7). The greatest quartile of NT-proBNP was associated with a nearly threefold odds of LVH (odds ratio 2.7, 95% confidence interval [CI] 1.8 to 4.0) and LV systolic dysfunction (odds ratio 2.7, 95% CI 1.7 to 4.5) and a twofold odds of diastolic dysfunction (odds ratio 2.0, 95% CI 1.3 to 2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve 0.66) and LV systolic dysfunction (area under the curve 0.62) and poorly for the detection of diastolic dysfunction (area under the curve 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants' likelihood of having LVH (net reclassification improvement 0.14, 95% CI 0.13-0.15; p <0.001) and LV systolic dysfunction (net reclassification improvement 0.28, 95% CI 0.27 to 0.30; p <0.001) but not diastolic dysfunction (net reclassification improvement 0.10, 95% CI 0.10 to 0.11; p = 0.07). In conclusion, in this large chronic kidney disease cohort without heart failure, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction.

Topics: Adult; Aged; Cross-Sectional Studies; Echocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Protein Precursors; Renal Insufficiency, Chronic; Retrospective Studies; Severity of Illness Index; United States; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

To evaluate the association of left ventricular (LV) diastolic function and N-terminal pro-brain natriuretic peptide (NT-proBNP) with renal function in essential hypertension.. LV diastolic function was estimated by the ratio of early diastolic velocities (E) from transmitral inflow to early diastolic velocities (E') of tissue Doppler at mitral annulus (septal corner); NT-proBNP was measured in 207 hypertensive patients (mean age 56±14 years). The subjects were classified into 3 groups: E/E'≤10 group (n = 48), 1015 group (n = 50). The renal function was estimated by glomerular filtration rate (GFR) with (99m)Tc-DTPA. GFR from 30 to 59 ml/min/1.73 m(2) was defined as Stage 3 chronic kidney disease (CKD). GFR was also estimated using the modified MDRD equation. Albuminuria was defined by urinary albumin/creatinine ratio (UACR).. GFR was lower and UACR was higher in E/E' >15 group than in 10< E/E' ≤15 group or E/E' ≤10 group (p<0.0001), GFR was significantly negative and UACR was positive correlated with E/E' and NT-proBNP (p<0.0001). In multivariate stepwise linear analysis, GFR had significant correlation with age (p = 0.001), gender (p = 0.003), E/E' (p = 0.03), lgNT-proBNP (p = 0.001) and lgUACR (p = 0.01), while eGFR had no significant correlation with E/E' or lgNT-proBNP. Multivariate logistic regression analysis, adjusted for potential confounding factors, showed that participants in E/E'>15 group were more likely to have Stage 3 CKD compared with those in E/E'≤10 group with an adjusted odds ratio of 8.31 (p = 0.0036).. LV diastolic function, assessed with E/E' and NT-proBNP is associated with renal function in essential hypertension.

Topics: Adult; Diastole; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Risk Factors; Ventricular Dysfunction, Left

N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels are associated with congestive heart failure severity, and are an important diagnostic tool for assessing patients with acute dyspnea. Reduced renal function increases NT-proBNP concentrations, and therefore it might be a confounding factor in chronic kidney disease (CKD) patients.. The aim of the present study was to relate NT-proBNP plasma levels to different stages of renal function assessed with different methods in older adult subjects admitted because of dyspnea.. NT-proBNP plasma levels (Roche Diagnostic, Mannheim, Germany) were measured in 134 older adult patients (age: 80 ± 6 years) admitted to hospital because of dyspnea. Anthropometrics, anamnesis, and biochemical data were collected. Glomerular filtration rate (GFR) was evaluated with different equations, the 4 variables MDRD equations (GFR(MDRD186), GFR(MDRD175)), Mayo Clinic Quadratic formula (GFR(MAYO)), and the new CKD-EPI formula (GFR(CKD-EPI)). Patients were classified into the five K/DOQI stages of CKD and median NT-proBNP values were calculated evaluating their relationship with GFR.. Median NT-proBNP values were better stratified into the five K/DOQI stages by GFR(MAYO) (stage 1 (n = 10) 1,640 pg/ml vs. stage 2 (n = 61) 2,371 pg/ml vs. stage 3 (n = 42) 3,815 pg/ml vs. stage 4 (n = 18) 6,320 pg/ml vs. stage 5 (n = 3) 7,256 pg/ml, p = 0.017). However, similar results were obtained with the other formulae. NT-proBNP was negatively correlated with GFR as evaluated with all the different formulae (r -0.25 to -0.29; all p < 0.01). Multiple regression analysis confirmed the independent association between LnNT-proBNP and GFR.. NT-proBNP plasma levels progressively increase with worsening of renal function, and appear to be related to the five K/DOQI stages of CKD. For this purpose, GFR assessed with the GFR(MAYO) formula appears to better stratify NT-proBNP in older adult subjects. Renal function should be considered when interpreting NT-proBNP levels in older adult patients admitted for dyspnoea.

Topics: Aged; Aged, 80 and over; Aging; Dyspnea; Female; Glomerular Filtration Rate; Hospitalization; Humans; Kidney; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

Troponin T (TnT), brain natriuretic peptide (BNP) and its precursor (NT-proBNP) are useful markers of acute coronary events and heart failure. The aim of this study was to analyze the influence of chronic renal failure, inflammation and heart disease in these biomarkers.. In 266 patients with different stages of chronic renal diseases, the following parameters were measured: cardiac markers (TnT, BNP and NT-proBNP), renal function, inflammatory markers (hsCRP, fibrinogen, albumin, uric acid and white blood cells). We recorded the cardiovascular history. Ventricular dysfunction and left ventricular hypertrophy were assessed by echocardiography.. A significant correlation between cardiac markers and inflammatory parameters such as fibrinogen, hsCRP and albumin was found. Age (OR 1.05, P = .021), serum albumin (OR: 0.06, P=.006), ischemic heart disease (OR: 8.17, P=.0092) and renal failure (OR: 1.67, P=.05) were predictors of higher BNP levels. Age (OR 1.05, P=.0097), serum albumin (OR: 0.12, P=.001), ischemic heart disease (OR: 3.43, P=.034), renal failure (OR: 1, 65, P=.036) and heart failure (OR: 4.33, P=.0312) were predictors of elevated NT-proBNP. Previous ischemic heart disease alone increased TnT levels (OR: 6.51, P=.0012).. Age, previous cardiac disease and inflammation increase cardiac marker levels in patients with different stages of renal disease, but the degree of renal failure is an important factor influencing NT-proBNP levels. However, ischemic heart disease alone increases the levels of TnT.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Female; Heart Diseases; Humans; Inflammation; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Severity of Illness Index; Troponin T; Ultrasonography

Myocardial damage and strain are common in children with chronic renal failure. The most prevalent pathologies, as defined by echocardiography, are left ventricular hypertrophy (LVH), diastolic and systolic dysfunction, and altered LV geometry. Troponin I and T, as well as B-type natriuretic peptide (BNP) and its cleavage fragment NT-proBNP, are known to be good markers of myocardial damage and stress, respectively, in the general adult population and among those with chronic kidney disease (CKD). In this study we measured the levels of troponins I and T, BNP, and NT-proBNP in a group of children and young adults with CKD stages 3-5 and determined their respective correlations with echocardiographic and laboratory abnormalities. BNP and NT-proBNP levels and their log values correlated well with the following parameters: diastolic blood pressure, estimated glomerular filtration rate, time-averaged hemoglobin levels, and LV mass. Both BNP and NT-proBNP levels, but not those of either troponin, were found to be reliable surrogate markers of strained hearts, defined as having LVH or diastolic or systolic dysfunction, in the pediatric CKD stages 3-4 group. The log NT-proBNP value was also found to be a good marker of cardiac strain in the CKD stage 5 group of patients. Serum BNP and NT-proBNP threshold concentrations of 43 and 529 pg/ml, respectively, were found to have the best sensitivity and specificity in predicting strained hearts. Based on these findings, we conclude that both BNP and NT-proBNP levels, but not those of troponins I and T, can serve as inexpensive, simple, and reliable markers of stressed hearts in the pediatric CKD patient population.

Topics: Adolescent; Area Under Curve; Biomarkers; Child; Child, Preschool; Cross-Sectional Studies; Echocardiography, Doppler; Heart; Heart Diseases; Humans; Infant; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; ROC Curve; Sensitivity and Specificity; Troponin; Young Adult

The aim of the study was to evaluate the efficacy and clinical outcome of peritoneal dialysis (PD) treatment in patients with severe refractory heart failure (HF) and chronic kidney disease (CKD).. The PD treatment was performed in 118 patients [49.2% New York Heart Association (NYHA) III and 50.8% NYHA IV] with a mean age of 73.2 ± 11.4 years as an in-centre-based and intermittent automated PD at least three times per week for 12 h per session and followed up for 1.11 ± 1.17 years. The functional status of those surviving for 6 months improved (P < 0.0001): 18 (32.1%) of all 60 patients with NYHA IV at baseline died within 6 months, 3 (5.4%) converted to NYHA III, 33 (58.9%) to NYHA II, and 2 (3.6%) to NYHA I. In all 58 patients with NYHA III at baseline, 14 (25.0%) died within 6 months, 27 (48.2%) converted to NYHA II, 12 (21.4%) to NYHA I, and 3 (5.4%) showed no improvement. In those surviving for 6 months, fluid overload was significantly reduced as body weight decreased, from 78.7 [95% confidence interval (CI) 75.8-81.7] to 74.7 (71.5-77.9) after 6 months after multiple imputation (P < 0.001). The overall survival rates after 3, 6, and 12 months were 77% (95% CI 70-85), 71% (95% CI 62-79), and 55% (95% CI 45-64). In the multivariate analyses, age, diabetes mellitus, serum urea, and brain natriuretic peptide were significantly associated with mortality. The incidence of peritonitis and catheter dysfunction was 0.053 (95% CI 0.014-0.093) and 0.084 (95% CI 0.034-0.133), respectively.. The data suggest that PD is a safe, efficient, and well tolerated therapeutic tool for patients with refractory chronic HF and CKD.

Topics: Adult; Aged; Aged, 80 and over; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; New York; Peritoneal Dialysis; Prospective Studies; Regression Analysis; Renal Insufficiency, Chronic; Severity of Illness Index; Survival Rate; Treatment Outcome; Young Adult

Topics: Ambulatory Care; Female; Heart Failure; Humans; Kidney; Male; Natriuretic Peptide, Brain; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Renal Insufficiency; Renal Insufficiency, Chronic

Although brain natriuretic peptide (BNP) concentration has been associated with atherosclerosis and ischemic cardiovascular diseases (CVD) in the general population, less is known about this relationship in pre-dialysis chronic kidney disease (CKD) patients.. We prospectively analyzed 227 pre-dialysis patients with CKD [median estimated glomerular filtration rate (eGFR): 28.82 (11.65-48.20) ml/min/1.73 m(2)]. At enrollment, BNP concentrations, biochemical and echocardiographic parameters were measured, and carotid artery ultrasound was performed. Patients were prospectively followed for a mean 31.8 months (range 0.5-57.0 months). Ischemic CV events and patient outcomes were recorded.. Median BNP concentration at enrollment was significantly higher in the CKD patients than in a control group [53.9 (16.2-181.0) pg/ml vs. 9.4 (7.0-15.3) pg/ml, P<0.01]. BNP concentration was positively related with the carotid intima-media thickness of the common carotid artery (CCA-IMT) and left ventricular mass index (LVMI) and was significantly higher in patients with than without carotid plaques (P<0.01). Logistic regression analysis confirmed that lgBNP concentration was independently correlated with carotid plaques. Thirty-two patients experienced ischemic cardiovascular (ICV) events during follow-up. Kaplan-Meier analysis showed that cumulative survival without new ICV events was better in patients with lower than with higher BNP concentrations (P<0.01). Cox regression analysis showed that BNP was an independent risk factor for ICV events (HR=3.167, 95%CI=1.398-7.171, P<0.01).. Similar to findings in the general population, elevated BNP level is related to atherosclerosis and an increased risk of ICV events in pre-dialytic CKD patients.

Topics: Adult; Aged; Atherosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Plaque, Atherosclerotic; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors

As a cardiorenal syndrome, there is a dynamic interplay between the heart and the kidney. We conducted a prospective study to evaluate the prognostic impact of plasma B-type natriuretic peptide (BNP) level, a cardiac biomarker, on the long-term kidney prognosis in chronic kidney disease (CKD) patients.. We prospectively enrolled 508 patients with CKD Stages 3, 4 and 5 not on dialysis, from a single nephrology department between 2004 and 2010. The exclusion criteria were over 90 years of age, malignancy, active infection, low cardiac ejection fraction and rapid progressive glomerulonephritis. Relationships between BNP and kidney end point [defined as doubling of baseline serum creatinine and end-stage kidney disease (ESKD) requiring kidney replacement therapy] were measured using Cox models for case-mix and laboratory variables.. The final analysis covered 485 participants with no loss to follow-up. The median follow-up period was 3.2 years. Two hundred and twenty-eight of the 485 patients reached ESKD requiring dialysis, and baseline serum creatinine levels doubled in another 31. The kidney end point was significantly poorer among patients with plasma BNP levels above, compared with below a cut-off value of 86.1 pg/mL indicated from receiver operating characteristic analysis. Multivariable Cox regression analysis identified the common logarithm BNP as a predictor of kidney end point (adjusted hazard ratio 1.78, 95% CI: 1.28-2.46, P < 0.01).. Elevation of BNP level is associated with an increased risk for accelerated progression of CKD ultimately to ESKD. Monitoring the BNP level could be helpful in the management of combined heart and kidney disease.

Topics: Aged; Biomarkers; Disease Progression; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors

Our aim was to investigate left ventricular (LV) physiology and short-axis and long-axis regional LV myocardial function throughout the cardiac cycle with 2D-speckle tracking echocardiography (2D-STE) in patients with chronic kidney disease.. The study population consisted of 40 maintenance hemodialysis patients (hemodialysis group), 20 uremic patients hospitalized for creation of primary arteriovenous fistula (nondialysis group), and a control group of 20 healthy volunteers. LV regional longitudinal, circumferential and radial peak systolic velocity (Vs); early diastolic velocity (Ve); and peak systolic strain (ε) were measured with 2D-STE.. Increased LV wall thickness and a decreased E/A ratio were found in the nondialysis and hemodialysis groups as compared to the control group, but there was no difference between the 2 study groups. Longitudinal Vs and Ve of the LV basal segment and middle segment in hemodialysis group and nondialysis group were all slower than those in the control group, and Vs in the nondialysis group was slower than that of the hemodialysis group. Circumferential and radial Vs and Ve were not different among the 3 groups, except that the radial Vs of LV basal segment was markedly decreased in the nondialysis group. Longitudinal peak systolic strain in the hemodialysis and nondialysis groups were both decreased as compared to the control group. Circumferential and radial peak systolic strain was decreased only in the nondialysis group.. 2D-STE may be used to identify early abnormalities in patients with chronic kidney disease who have preserved LV ejection fraction. LV regional function appeared to be better in the hemodialysis group than that in the nondialysis group.

Topics: Aged; Blood Pressure; Calcium; Early Diagnosis; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic; Serum Albumin; Ventricular Dysfunction, Left

This study sought to determine the pharmacodynamic effect of modulation of volume status by withdrawal and reinstitution of diuretic treatment on markers of renal and tubular function.. Decreased renal perfusion and increased congestion are associated with renal dysfunction in patients with heart failure.. In this study, 30 patients with chronic systolic heart failure in a presumed euvolemic state and on standard oral furosemide therapy (40 to 80 mg) were examined. At baseline, subjects were withdrawn from their loop diuretics. After 72 h, their furosemide regimen was reinstated, and patients were studied again 3 days later. Serum creatinine, atrial and B-type natriuretic peptide, urinary kidney injury molecule (KIM)-1, urinary N-acetyl-beta-D-glucosaminidase (NAG), and serum as well as urinary neutrophil gelatinase-associated lipocalin (NGAL) were determined at various time points.. Diuretic withdrawal resulted in increases in atrial and B-type natriuretic peptide (both p < 0.05). Serum creatinine was unaffected. Both urinary KIM-1 (p < 0.001) and NAG (p = 0.010) concentrations rose significantly, after diuretic withdrawal, whereas serum and urinary NGAL were not significantly affected. After reinitiation of furosemide, both urinary KIM-1 and NAG concentrations returned to baseline (both p < 0.05), but NGAL values were unaffected.. Subclinical changes in volume status by diuretic withdrawal and reinstitution are associated with increases and decreases of markers of tubular dysfunction in stable heart failure. Diuretic therapy may favorably affect renal and tubular function by decreasing congestion.

Topics: Acetylglucosaminidase; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Comorbidity; Creatinine; Diuretics; Female; Furosemide; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Kidney Function Tests; Kidney Tubules; Male; Membrane Glycoproteins; Natriuretic Peptide, Brain; Receptors, Virus; Renal Insufficiency, Chronic

We studied relation between cystatin C level and risk of unfavorable outcome (unstable angina, fatal and nonfatal myocardial infarction [MI], fatal and nonfatal stroke, and death) in patients stabilized after exacerbation of ischemic heart disease. Patients (n=272) were included on day 10 after onset of acute coronary syndrome. No relationship between studied outcomes and cystatin was found in a group as a whole. In patients with normal of slightly reduced renal function (glomerular filtration rate more or equal 60 ml/min/1.73 m2) unfavorable outcomes were independently associated with history of myocardial infarction and stroke, elevated levels of brain natriuretic peptide and cystatin. In subjects with moderately or severely reduced renal function elevation of cystatin level lost its significance. Risk of development of unfavorable outcomes among these subjects was independently related to history of MI and GFR <60 ml/min/1.73 m2 (OR 2.130, 95% CI 1.010-4,489; =0,047). Our data confirm possibility of use of cystatin C level measured early after ACS in patients with normal or slightly lowered renal function as a parameter characterizing risk of cardiovascular complications and death.

Topics: Aged; Biomarkers; Comorbidity; Cystatin C; Disease Progression; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency, Chronic; Reproducibility of Results; Risk Factors; Time Factors

Novel biomarkers may help explain the pathobiology of vascular disease in chronic kidney disease, and thus set the stage for identification of therapeutic targets, potential reversibility, and improved outcomes in this population.. 124 subjects with GFR <60 ml/min or on renal replacement therapy underwent measurement of inflammatory, vascular and cardiac biomarkers as well as aortic pulse wave velocity (PWV) testing. A subset of patients (n = 60) had repeat PWV measured at 6 months.. Thirty-four percent of the patients were diabetic, and 50% had a history of cardiovascular disease or congestive heart failure. Median PWV was 9.8 (IQR 8.3-12.7) m/s. No significant correlations between the measured biomarkers and baseline PWV was observed. An increase in PWV (>1.5 m/s) over 6 months was observed in those subjects with diabetes, a higher brain natriuretic peptide level, lower cholesterol and lower phosphate level. Age (HR 1.086, p = 0.0028), fetuin (0.024, p = 0.0448), and interleukin-10 (top tertile HR 4.720, p = 0.0359) were associated with mortality.. In this cohort of patients with chronic kidney disease and diabetes and/or heart disease, we were unable to demonstrate that select biomarkers can inform processes leading to vascular disease. Biomarkers do appear to have utility in predicting future events in this population.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein; Aorta; Biomarkers; Blood Flow Velocity; Blood Pressure; Cardiovascular Diseases; Cholesterol; Comorbidity; Diabetes Mellitus; Female; Humans; Interleukin-10; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Phosphates; Proportional Hazards Models; Prospective Studies; Pulsatile Flow; Renal Insufficiency, Chronic; Severity of Illness Index; Vascular Stiffness

Elevation of the plasma level of B-type natriuretic peptide (BNP) is commonly seen in patients with chronic kidney disease (CKD), but its significance remains unclarified. We conducted a prospective study to evaluate the role of plasma BNP level as a predictive marker of renal outcome.. 237 patients with CKD stage 3, 4 not on dialysis were prospectively enrolled as a hospital cohort from August 2004 to December 2008. Combined renal endpoint was doubling of baseline serum creatinine or end-stage renal disease requiring dialysis. Endpoint free renal survival was calculated by Kaplan Meier analysis and compared by the log-rank test. We used Cox proportional hazards analysis to determine the independent predictor for renal outcome among the clinical data at the time of referral to a nephrologist. ROC analysis was used to determine the best cut-off value of plasma BNP level to predict the renal outcome.. The mean follow-up period was 2.5 +/- 1.1 years. Median age was 65 years. Of the subjects, 65.8% were men and 37.9% had diabetes mellitus. Median serum creatinine level was 2.7 mg/dL. Plasma BNP level was significantly higher among 147 patients who reached the combined renal endpoint compared with 90 patients who did not (116.0 pg/mL vs 54.5 pg/mL, p<0.001). After adjustment with other established predictive factors of renal outcome, plasma BNP level was selected to be the strongest predictive marker for renal endpoint (Hazard ratio 1.173, 95%CI 1.000-1.376). The optimal cut-off value of plasma BNP level suggested by ROC analysis was 69.5 pg/mL. Patients with a plasma BNP level above the cut-off point revealed a significantly poor renal outcome compared with those with a plasma BNP level below the cut-off point.. The present study suggests that the plasma BNP level might be a predictive marker for renal outcome and a guide for management of cardio-renal interaction.

Topics: Aged; Biomarkers; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency, Chronic

The N-amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels are indicative of heart failure. Few correlates of NT-proBNP levels have been identified in persons with moderate chronic kidney disease (CKD), and data from those without heart failure and from African Americans are especially limited.. The African American Study of Kidney Disease and Hypertension (AASK) enrolled nondiabetic African Americans with hypertensive kidney disease (glomerular filtration rate [GFR] = 20-65 ml/min/1.73 m(2)) and no evidence of clinical heart failure. NT-proBNP was measured in 982 AASK participants.. In unadjusted analyses, GFR (r = -0.39; p < 0.001), hematocrit (r = -0.21; p < 0.001) and body mass index (BMI; r = -0.07; p = 0.04) were inversely correlated, and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p < 0.001) were positively correlated with log NT-proBNP levels. After adjustment for potential confounders, lower GFR and hematocrit and higher systolic blood pressure and protein:creatinine ratio remained significantly associated with higher NT-proBNP.. Lower GFR and hematocrit, and higher urinary protein excretion may be associated with volume expansion in CKD. These results suggest that these processes are associated with increased NT-proBNP in CKD and may play a role in the development of heart failure.

Topics: Adult; Aged; Black or African American; Body Mass Index; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Hematocrit; Humans; Hypertension, Renal; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proteinuria; Renal Insufficiency, Chronic; Risk Factors

A-type natriuretic peptide (ANP) and adrenomedullin (ADM) are potent hypotensive, diuretic, and natriuretic peptides involved in maintaining cardiovascular and renal homeostasis. We conducted a prospective 7-year study of 177 nondiabetic patients with primary chronic kidney disease to see if ANP and ADM plasma concentrations predict the progression of their disease, using novel sandwich immunoassays covering the midregional epitopes of the stable prohormones (MRproANP and MR-proADM). Progression of chronic kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure, which occurred in 65 patients. Analysis of the receiver operating characteristic curve for the prediction of renal endpoints showed similar areas under the curve for the glomerular filtration rate (GFR) (0.838), MR-proANP (0.810), and MRproADM (0.876), respectively, as did the Kaplan-Meier curve analyses of the patients stratified according to the median of the respective markers. In separate multiple Cox-proportional hazard regression analyses, increased plasma concentrations of both peptides were each strongly predictive of the progression of chronic kidney disease after adjustments for age, gender, GFR, proteinuria and amino-terminal pro-B-type natriuretic peptide. Our study suggests that MR-proANP and MR-proADM are useful new markers of progression of primary nondiabetic chronic kidney disease.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Biomarkers; Disease Progression; Glomerular Filtration Rate; Humans; Immunoassay; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; ROC Curve; Young Adult

The natriuretic peptide (NP) system plays a central role in the renal adaptations to acute volume expansion. However, the modulation of the NP system in chronic renal insufficiency (CRI) remains to be elucidated. In the present study, we evaluated cardiac haemodynamics, plasma type-B natriuretic peptide (BNP) levels and the expression of natriuretic peptide receptor A (NPR-A) and NPR-C in the renal cortex (RC) and medulla (RM) of Sham and (3/4) nephrectomized ((3/4)nx) rats, up to 26 weeks after surgery.. Male Wistar-Han rats (190-220 g; n = 49) were randomly assigned to (3/4)nx or Sham surgery. Two, 10 and 26 weeks after surgery, non-invasive blood pressure (BP) and left ventricular (LV) haemodynamics were performed, and urine and blood were collected for metabolic studies and plasma BNP determination. In addition, tissue samples from RC and RM were obtained for NPR-A and NPR-C quantification (RT-PCR and western blotting) as well as NPR-A immunodetection.. In (3/4)nx rats, the progressive interstitial fibrosis and tubular atrophy were accompanied by a time-dependent increase of BP and impaired natriuretic response to volume expansion (VE). This was accompanied in (3/4)nx rats by an early and time-dependent elevation of BNP circulating levels that was not associated with cardiac dysfunction or increased myocardial BNP gene expression. In (3/4)nx rats, NPR-A expression in the remnant RM was consistently reduced at 2, 10 and 26 weeks, and this was accompanied by an increase in NPR-C expression in the remnant RC from (3/4)nx rats.. BP elevation and compromised natriuretic response to VE in (3/4)nx rats is associated with increased circulating BNP levels in the absence of cardiac dysfunction. This is accompanied in (3/4)nx rats by both impaired NPR-A expression in the RM and upregulation of NPR-C in the RC suggesting a novel mechanism for NP resistance in CRI.

Topics: Animals; Base Sequence; Blood Volume; Coronary Circulation; DNA Primers; Hemodynamics; Kidney Cortex; Kidney Medulla; Male; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptides; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor; Renal Insufficiency, Chronic; RNA, Messenger

Topics: Biomarkers; Heart Arrest; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renal Dialysis; Renal Insufficiency, Chronic

Limited data are available regarding the diagnostic and prognostic utility of brain natriuretic peptide (BNP) in patients with chronic kidney disease (CKD) in the intensive care unit (ICU) setting.. All patients with CKD and a serum creatinine (Cr) of 2.0 mg/dl or higher admitted to the ICU between January 2006 and September 2007 were enrolled in this study. The CKD group was divided according to the presence or absence of acute decompensated heart failure (ADHF) into CKD + ADHF and CKD-ADHF groups, respectively. Other patients with ADHF having low Cr (<1.2 mg/dl) in the coronary care unit were also recruited as a control group during the same period. BNP levels at the time of admission (admission BNP) were compared amongst these groups. We then sought to determine whether BNP levels could predict the outcome in patients with CKD.. Of 136 patients with CKD for whom data were available, including 58 on dialysis (42.6%), 81 (59.6%) had ADHF and their estimated glomerular filtration rate (eGFR) was 12.8 +/- 7.3 ml/min/1.73 m2. BNP levels at admission were 2708.6 +/- 1246.9, 567.9 +/- 491.7 and 1418.9 +/- 1126.5 pg/ml in the CKD + ADHF, CKD - ADHF and control groups (n = 33), respectively (P = 0.000). The optimal cutoff level in patients with CKD was 1020.5 pg/ml (area under the curve = 0.944) to detect ADHF from the receiver operating characteristic (ROC) curve. This level was not associated with in-hospital mortality, all-cause death or a composite event (all-cause death and/or new cardiac event). However, a borderline significant association was observed with new cardiac events (hazard ratio (HR) = 4.551; P = 0.078) during the follow-up period (521.1 +/- 44.7 days). Furthermore, continuous variables of BNP and BNP quartiles were significantly associated with new cardiac events in the multivariate Cox model (HR = 1.001, P = 0.041; HR = 2.212, P = 0.018).. The findings suggest that the level of BNP at the time of admission may be a useful marker for detecting ADHF and predicting cardiac events in patients with CKD in the ICU setting.

Topics: Aged; Biomarkers; Female; Heart Failure; Hospital Mortality; Humans; Intensive Care Units; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; ROC Curve; Survival Analysis

Both serum cardiac troponin T (cTnT) and renal function are prognostic predictors in patients with chronic heart failure (CHF). We aimed to evaluate the relationship between renal function and serum cTnT.. We measured serum concentrations of cTnT in the aortic root (AO) and coronary sinus (CS) in 258 CHF patients. Patients were divided into two groups: patients with an estimated glomerular filtration rate (eGFR) >or= 60 mL/min/1.73 m(2) [chronic kidney disease (CKD)(-)], and patients with an eGFR < 60 mL/min/1.73 m(2) [CKD (+)]. In 32 (12%) of the 258 CHF patients, serum levels of cTnT were detectable (>or=0.03 ng/mL) in the AO and in the CS. There was no correlation between eGFR and the transcardiac increase in cTnT and there was a significant negative correlation between eGFR and the serum cTnT concentration (r = - 0.365, P = 0.039). There was no difference in the transcardiac gradient of cTnT between patients without CKD (n = 16) and patients with CKD (n = 16) (0.083 +/- 0.11 vs. 0.108 +/- 0.13 ng/mL, P = 0.55). However, the serum cTnT level in the AO was two-fold higher in CHF patients with CKD than patients without CKD (0.20 +/- 0.177 vs. 0.088 +/- 0.065 ng/mL, P < 0.05).. These findings indicate that decreased clearance via the kidney contributes to the elevated cTnT in CHF patients with CKD.

Topics: Aged; Case-Control Studies; Coronary Sinus; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Renal Insufficiency, Chronic; Risk Factors; Troponin T

Anemia is common in patients with chronic kidney disease (CKD) and contributes to cardiovascular alterations. Recent findings suggest that B-type natriuretic peptide (BNP) is a sensitive biomarker for left ventricular dysfunction, but relationship between hemoglobin and BNP in CKD patients is unclear. Hemoglobin, plasma BNP and serum creatinine levels were measured in 49 patients with CKD (without heart failure), divided in two groups according to the hemoglobin status (cut-off point 110 g/L). All patients underwent echocardiography in order to assess left ventricular (LV) morphology and function. The results showed that in the group of patients with hemoglobin levels under 110 g/L BNP levels were significantly elevated (p < 0.001), as well as left ventricular mass index (p < 0.001). Systolic and diastolic LV function were significantly better in patients with hemoglobin levels above 110 g/L (p < 0.001). Hemoglobin levels were inversely related to BNP values (r = -0.451, p < 0.001). Significantly negative correlation between BNP level and creatinine clearance (p = 0.009), and significantly positive correlation between BNP level and left ventricular mass index (LVMI) were established. A similar but positive relationship was observed between hemoglobin levels and creatinine clearance (p < 0.01). We established statistically significant negative correlation between hemoglobin levels and LVMI (r = -0.564, p < 0.001). In conclusion, BNP and hemoglobin levels depend on the renal function. Anemia may contribute to elevated BNP levels in CKD patients, and may represent an important confounder of the relationship between BNP and cardiac alteration in these patients.

Topics: Anemia; Biomarkers; Bosnia and Herzegovina; Creatinine; Echocardiography; Female; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic

Plasma concentrations of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are diagnostic and prognostic biomarkers of heart failure and are also increased in patients with chronic kidney disease (CKD). We examined the relevance of BNP and NT-proBNP as predictors of CKD progression.. Of 227 nondiabetic patients with mild-to-moderate renal insufficiency, 177 patients ages 18-65 years were followed in a prospective multicenter cohort study for a period of < or = 7 years. CKD progression was assessed by recording renal endpoints, defined as doubling of baseline serum creatinine or end-stage renal disease (ESRD) requiring renal replacement therapy.. BNP and NT-proBNP were significantly higher among 65 patients who reached the combined renal endpoint than among the 112 who did not [median (interquartile range) 61 (27-98) ng/L vs 39 (20-70) ng/L, P = 0.023, for BNP; 320 (117-745) ng/L vs 84 (44-176) ng/L, P <0.001, for NT-proBNP)]. Each increment of 1 SD in log-transformed BNP and NT-proBNP increased the risk of CKD progression by hazard ratios of 1.38 (95% CI 1.09-1.76, P = 0.009) and 2.28 (1.76-2.95, P <0.001), respectively. After adjustment for other established prognostic factors of CKD progression, NT-proBNP but not BNP remained a significant independent predictor of the combined renal endpoint.. Increased BNP and NT-proBNP concentrations indicate an increased risk for accelerated progression of CKD to ESRD and may prove to be valuable biomarkers for the assessment of prognosis in patients with CKD.

Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Renal Insufficiency, Chronic