Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure

In AL amyloidosis prognosis depends on the severity of heart dysfunction which is best assessed by natriuretic peptides (BNP and NT-proBNP). However, their clearance relies on glomerular filtration rate (GFR) and their concentration increases with renal failure. We evaluated the diagnostic and prognostic performance of NT-proBNP and BNP in 248 patients with AL amyloidosis with different degrees of renal failure. Patients were grouped according to GFR. Group 1 comprised 109 patients with GFR ≥60 mL/min/1.73 m(2) , Group 2, 77 subjects with GFR <60 and ≥15 mL/min/1.73 m(2) , and Group 3, 62 patients with GFR <15 mL/min/1.73 m(2) . The ability of natriuretic peptides to detect heart involvement and to predict survival in the three groups was assessed. Decreasing eGFR required higher cutoffs of both NT-proBNP and BNP for detecting heart involvement and predicting survival. Both natriuretic peptides were independent prognostic markers in Groups 1 and 2, whereas in Group 3 only BNP independently predicted survival. Natriuretic peptides are powerful and useful markers of cardiac dysfunction and prognosis, provided that eGFR is considered in interpreting their clinical meaning. BNP should be preferred in patients with end-stage renal failure.     

Relationship between B-type natriuretic peptides and pulmonary capillary wedge pressure in the intensive care unit

OBJECTIVES: We examined whether B-type natriuretic peptides (BNP) can serve as noninvasive markers of pulmonary capillary wedge pressure (PCWP) in the setting of critical illness. BACKGROUND: The BNP and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are highly correlated with left ventricular (LV) filling pressures in patients with depressed LV systolic function. However, their relationship to PCWP in a heterogeneous intensive care unit (ICU) population has not been established. METHODS: We prospectively studied 40 patients in the ICU requiring invasive hemodynamic monitoring. Hemodynamics were recorded simultaneously with blood sampling for BNP and NT-proBNP. RESULTS: The BNP (median 420 pg/ml) and NT-proBNP (median 3,304 pg/ml) levels were markedly elevated, but weakly correlated with PCWP (BNP, r = 0.40, NT-proBNP, r = 0.32) and other cardiac parameters. Peptide levels were approximately four-fold greater in patients with impaired (estimated glomerular filtration rate [eGFR] <60 ml/min) versus normal (eGFR >60 ml/min) renal function, despite similar PCWP, cardiac index, and LV ejection fraction. In addition, both BNP and NT-proBNP showed stronger correlations with PCWP in patients with preserved (BNP, r = 0.58, NT-proBNP, r = 0.73) versus impaired renal function (BNP, r = 0.48, NT-proBNP, r = 0.34). Interaction terms between eGFR and BNP (p = 0.06) and NT-proBNP (p = 0.04) suggest that eGFR modulates the relationship of these peptides to filling pressures. CONCLUSIONS: The BNPs are markedly elevated, yet show only weak correlations to PCWP in ICU patients requiring invasive hemodynamic monitoring. Thus, a single value for BNP or NT-proBNP may not be a clinically useful noninvasive marker of filling pressures in the critically ill patient. This appears to be especially true in patients with impaired renal function.     

Amino-terminal pro-brain natriuretic Peptide, renal function, and outcomes in acute heart failure: redefining the cardiorenal interaction?

OBJECTIVES: We sought to study the individual and integrative role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and parameters of renal function for prognosis in heart failure. BACKGROUND: Amino-terminal pro-BNP and renal impairment both predict death in patients with heart failure. Worsening of renal function in heart failure even defines the "cardiorenal syndrome." METHODS: Seven hundred twenty subjects presenting with acute heart failure from 4 university-affiliated medical centers were dichotomized according to NT-proBNP concentration and baseline glomerular filtration rate. In addition, patients were divided according to changes in renal function. The primary end point was 60-day mortality. RESULTS: The combination of a glomerular filtration rate (GFR) <60 ml/min/1.73 m2 with an NT-proBNP >4,647 pg/ml was the best predictor of 60-day mortality (odds ratio 3.46; 95% confidence interval 2.13 to 5.63). Among subjects with an NT-proBNP above the median, those with a GFR <60 ml/min/1.73 m2 or a creatinine rise > or =0.3 mg/dl had the worst prognosis, whereas in subjects with a NT-proBNP below the median, prognosis was not influenced by either impaired renal function at presentation or the development of renal impairment during admission. CONCLUSIONS: The combination of NT-proBNP with measures of renal function better predicts short-term outcome in acute heart failure than either parameter alone. Among heart failure patients, the objective parameter of NT-proBNP seems more useful to delineate the "cardiorenal syndrome" than the previous criteria of a clinical diagnosis of heart failure.     

Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study.

The relationship between renal insufficiency and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels remains unclear. We examined this relationship in the context of patients who presented to the emergency department of an urban tertiary care medical center with dyspnea. Even in the presence of renal insufficiency, NT-proBNP remained a valuable tool for the diagnosis of acute congestive heart failure and it provides important prognostic information. OBJECTIVES: We sought to examine the interaction between renal function and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels. BACKGROUND: The effects of renal insufficiency on NT-proBNP among patients with and without acute congestive heart failure (CHF) are controversial. We examined the effects of kidney disease on NT-proBNP-based CHF diagnosis and prognosis. METHODS: A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min were analyzed. We used multivariate logistic regression to examine covariates associated with NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of NT-proBNP concentration. RESULTS: Glomerular filtration rates ranged from 15 ml/min/1.73 m2 to 252 ml/min/1.73 m2. Renal insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were more likely to have CHF (all p < 0.003). Worse renal function was accompanied by cardiac structural and functional abnormalities on echocardiography. We found that NT-proBNP and GFR were inversely and independently related (p < 0.001) and that NT-proBNP values of > 450 pg/ml for patients ages <50 years and >900 pg/ml for patients > or =50 years had a sensitivity of 85% and a specificity of 88% for diagnosing acute CHF among subjects with GFR > or =60 ml/min/1.73 m2. Using a cut point of 1,200 pg/ml for subjects with GFR <60 ml/min/1.73 m2, we found sensitivity and specificity to be 89% and 72%, respectively. We found that NT-proBNP was the strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence interval 1.2 to 2.0; p = 0.0004) and remained so even in those with GFR <60 ml/min/1.73 m2 (hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p = 0.006). CONCLUSIONS: The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with suspected CHF, irrespective of renal function.     

Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure

BACKGROUND: Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels, but this has not been well described in heart failure (HF) patients without the exclusion of patients with renal dysfunction. AIMS: To study the influence of both anaemia and renal function on BNP and NT-proBNP levels in a large group of hospitalised HF patients. METHODS AND RESULTS: We studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159) were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non-anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were measured in all patients before discharge. In multivariable analyses both plasma haemoglobin and eGFR were independently related to the levels of BNP and NT-proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP] respectively, P-values<0.01). CONCLUSION: Anaemia and renal dysfunction are related to increased BNP and NT-proBNP levels, independent of the severity of HF. These results indicate that both anaemia and renal dysfunction should be taken into consideration during the interpretation of BNP and NT-proBNP levels in HF patients.     

Effect of compensated renal dysfunction on approved heart failure markers: direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP

Brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are markers of heart failure. Although renal dysfunction may increase plasma concentrations, the magnitude of this effect has not been assessed in a head-to-head comparison between the clinically approved tests. We assessed the effect of compensated renal dysfunction on BNP (Triage BNP; Biosite) and NT-proBNP (elecsys proBNP; Roche) in 469 randomly selected stable outpatients after myocardial infarction (MI; Monitoring Trends and Determinants in Cardiovascular Diseases [MONICA] register Augsburg) who were characterized with respect to renal function (glomerular filtration rate [GFR]; Cockroft method) and left ventricular (LV) ejection fraction (EF) and mass (2D echocardiography). BNP and NT-proBNP were elevated in MI patients with LV dysfunction (LVD; EF <35%) compared with MI patients with preserved EF ( >45%; BNP 139+/-27 pg/mL versus 75+/-6; NT-proBNP 816+/-237 pg/mL versus 243+/-20; both P <0.03). Among all MI patients, the prevalence of renal dysfunction (GFR <85 mL/min) was 24%. BNP and NT-proBNP were significantly elevated in MI patients with renal dysfunction (BNP 132+/-17 pg/mL versus 68+/-4 without renal dysfunction; NT-proBNP 535+/-80 pg/mL versus 232+/-19; both P <0.05), and both markers were correlated with GFR in univariate and multivariate analyses (all P <0.01). When binary cut-off values were stratified according to the absence or presence of renal dysfunction (BNP 75 pg/mL and 125 pg/mL, respectively; NT-proBNP 100 pg/mL and 350 pg/mL, respectively), the predictive power of both markers for the detection of LVD increased substantially. BNP and NT-proBNP are almost similarly influenced by mild-to-moderate renal dysfunction. Renal dysfunction is a potential cause of elevated marker concentrations in the absence of LVD, and cut-off concentrations should be stratified according to renal function.     

B-Type Natriuretic Peptide and Renal Disease

B-type natriuretic peptide (BNP) is a cardiac neurohormone which has a principal effect on the kidney to signal both natriuresis and diuresis. Both BNP and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, the relationships between BNP, renal function, and CHF as an emergency diagnosis, are not completely understood. The correlation between BNP and estimated glomerular filtration rate (eGFR) is approximately r = –0.20. At an eGFR <60 ml/min/1.73 m², the optimum cutpoint for BNP to diagnose CHF rises to approximately 200 pg/ml. At this cutpoint the area under the receiver operating characteristic curve is 0.81, indicating that BNP is of diagnostic value in this group. Importantly, the precursor molecule N-terminal proBNP has a stronger correlation with eGFR of approximately –0.60, and is influenced by the age-related decline in renal function above the lower bounds of normal of <60 ml/min/1.73 m². Because BNP is a principal messenger from the heart to the kidneys, and because it is influenced by renal filtering function, parenchymal mass, and tubular function, BNP can be leveraged in assisting in the diagnosis and management of combined heart and renal failure.     

Association between renal function and circulating levels of natriuretic peptides (from the Dallas Heart Study)

The relations between renal function and circulating B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-pro-BNP) in the general population have not been fully elucidated. A total of 2,784 subjects from the Dallas Heart Study, a multiethnic population-based sample of Dallas County, Texas, residents, was studied. Detailed cardiac phenotyping, including magnetic resonance imaging and electron beam computed tomography, as well as measurements of NT-pro-BNP and BNP, were performed. Associations between estimated glomerular filtration rate (eGFR) and both NT-pro-BNP and BNP were evaluated using multivariable statistical analysis techniques. Median eGFR in this young, predominantly healthy population was 97 ml/min/1.73 m(2) (interquartile range 84 to 112). Natriuretic peptide levels were not associated with renal function over the normal range of eGFR. Below a threshold eGFR of 90 ml/min/1.73 m(2), both NT-pro-BNP and BNP increased in an exponential fashion with decreasing eGFR. These associations remained significant after adjustment for multiple potential confounders (p <0.001 for all). For eGFR <90 ml/min/1.73 m(2), the relative increase in NT-pro-BNP was twice as great as that for BNP for a given decrease in eGFR. In conclusion, a threshold effect regarding the association between renal function and natriuretic peptides was shown. With eGFR <90 ml/min/1.73 m(2), both NT-pro-BNP and BNP were inversely and independently associated with renal function, with a greater magnitude of association with renal impairment noted for NT-pro-BNP.     

Kidney function and cardiovascular disease in the hypertensive population: the ERIC-HTA study

BACKGROUND AND OBJECTIVES: Epidemiological data on the incidence and prevalence of cardiovascular disease in chronic renal failure are scant The objective of the present study is to assess the relationship between renal function, measured by the estimated glomerular filtration rate, and the presence of early or established cardiovascular disease, in a population of hypertensives from primary care. PATIENTS AND METHODS: Cross-sectional, multicentre study carried out in primary care centres all over Spain. Hypertensive subjects, older than 55 years, were included. In all of them a structured interview including cardiovascular risk factors or disease was performed. Blood pressure was measured following a standard procedure, and serum biochemistry and an electrocardiogram were obtained. Renal function was estimated using the abbreviated MDRD (Modification of Diet in Renal Disease Study Group) equation. For each glomerular filtration rate stratum the odds ratio and 95% confidence interval (CI) of left ventricular hypertrophy or cardiovascular disease were calculated, adjusted by confounding variables. RESULTS: A total of 13 687 patients (mean age 68.1 years, women 55.4%, diabetics 30.6%, body mass index 28.6 kg/m2) were included. Of these, 26.4% had established cardiovascular diseases and 20.3% electrocardiographic left ventricular hypertrophy. The average serum creatinine was 1.01 mg/dl, creatinine clearance 70.0 ml/min, and glomerular filtration rate 74.0 ml/min per 1.73 m2. Thirty-three patients (0.24%) had glomerular filtration rate < 5 ml/min per 1.73 m2; 89 (0.65%) from 15 to 29; 3745 (27.36%) from 30 to 59; 7798 (56.97%) from 60 to 89; and 2019 (14.75%) higher than 89 ml/min per 1.73 m2. In a multiple regression analysis, after adjusting by age, sex, body mass index, diabetes, systolic and diastolic blood pressure, and smoking, a lower glomerular filtration rate was associated with a higher prevalence of left ventricular hypertrophy. Likewise, a reduction in the glomerular filtration rate was also associated with a higher prevalence of cardiovascular disease. CONCLUSIONS: In hypertensive patients from primary care, the prevalence of cardiovascular disease is inversely proportional to the level of renal function. Estimated glomerular filtration is easy to determine and complements evaluation of the hypertensive patient.     

Glomerular filtration rate estimated by the CKD-EPI formula is a powerful predictor of in-hospital adverse clinical outcomes after an acute coronary syndrome

The prognostic value of admission estimated glomerular filtration rate (eGFR) calculated by the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for cardiovascular adverse outcomes in acute coronary syndrome (ACS) was explored. Baseline eGFR was classified as no renal dysfunction (>90 mL/min per 1.73 m(2)), borderline (90-60.1 mL/min per 1.73 m(2)), moderate (60-30.1 mL/min per 1.73 m(2)), or severe (≤30 mL/min per 1.73 m(2)) renal dysfunction. Of the 5034 patients, 3415 (67.8%) had eGFR <90. Compared to patients with an eGFR ≥60 mL/min per 1.73 m(2), patients with <60 mL/min per 1.73 m(2) were less likely to be treated with β-blockers, angiotensin-converting enzyme inhibitors, or statins, or to undergo percutaneous coronary interventions. Lower eGFR showed a stepwise association with significantly worse adverse in-hospital outcomes. The adjusted odds ratio of in-hospital death with an eGFR <30 mL/min per 1.73 m(2) was 3.1 (95% confidence interval 1.1-8.4, P = .0324), compared with an eGFR >90 mL/min per 1.73 m(2). Estimated glomerular filtration rate calculated by the new CKD-EPI is an independent predictor of major adverse cardiac outcomes in patients with ACS.     

Clinical profile and management of hypertensive patients with chronic ischemic heart disease and renal dysfunction attended by cardiologists in daily clinical practice

OBJECTIVE: The present study was designed to assess the influence of renal function on the clinical profile and management of the hypertensive outpatients with chronic ischemic heart disease. METHODS: A total of 112 investigators, all cardiologists, were asked to consecutively enrol outpatients of at least 18 years of age, both sexes, with an established diagnosis of hypertension and chronic ischemic heart disease. Renal function was assessed by serum creatinine levels and estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula. Renal impairment was considered a serum creatinine of at least 1.2/1.3 mg/dl (women/men) or an estimated glomerular filtration rate less than 60 ml/min/1.73 m2. Blood pressure was considered controlled when it was less than 140/90 mmHg and less than 130/80 mmHg in diabetic patients or patients with chronic kidney disease. RESULTS: A total of 2024 patients (66.8+/-10.1 years; 31.7% women) were included. A total of 666 (32.9%) and 498 (24.6%) patients exhibited renal function impairment assessed by estimated glomerular filtration rate and serum creatinine, respectively. The subgroup of patients with renal dysfunction was older, with a higher proportion of women with atrial fibrillation, diabetes, organ damage, associated clinical conditions and a worse blood pressure control. No differences were found in clinical profile when the two subgroups of patients with impaired renal function [serum creatinine >or=1.2/>or=1.3 mg/dl (women/men) vs. estimated glomerular filtration rate <60 ml/min per 1.73 m2] were compared. CONCLUSION: Renal function impairment is frequent in the hypertensive population with coronary artery disease. Patients with renal dysfunction represent a subgroup of very high-risk population with more risk factors and comorbidities and worse blood pressure control. The clinical profiles of hypertensive patients with renal function impairment are similar whether renal dysfunction is detected by high serum creatinine or by low estimated glomerular filtration rate.     

Influence of renal function on the usefulness of N-terminal pro-B-type natriuretic peptide as a prognostic cardiac risk marker in patients undergoing noncardiac vascular surgery

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is related to stress-induced myocardial ischemia and/or volume overload, both common in patients with renal dysfunction. This might compromise the prognostic usefulness of NT-pro-BNP in patients with renal impairment before vascular surgery. We assessed the prognostic value of NT-pro-BNP in the entire strata of renal function. In 356 patients (median age 69 years, 77% men), cardiac history, glomerular filtration rate (GFR, ml/min/1.73 m(2)), and NT-pro-BNP level (pg/ml) were assessed preoperatively. Troponin T and electrocardiography were assessed postoperatively on days 1, 3, 7, and 30. The end point was the composite of cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariate analysis was used to evaluate the interaction between GFR, NT-pro-BNP and their association with postoperative outcome. Median GFR was 78 ml/min/1.73 m(2) and the median concentration of NT-pro-BNP was 197 pg/ml. The end point was reached in 64 patients (18%); cardiac death occurred in 7 (2.0%), Q-wave myocardial infarction in 34 (9.6%), and non-Q-wave myocardial infarction in 23 (6.5%). After adjustment for confounders, NT-pro-BNP levels and GFR remained significantly associated with the end point (p = 0.005). The prognostic value of NT-pro-BNP was most pronounced in patients with GFR > or =90 (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.80 to 1.76) compared with patients with GFR 60 to 89 (OR 1.04, 95% CI 1.002 to 1.07), and with GFR 30 to 59 (OR 1.12, 95% CI 1.03 to 1.21). In patients with GFR <30 ml/min/1.73 m(2), NT-pro-BNP levels have no prognostic value (OR 1.00, 95% CI 0.99 to 1.01). In conclusion, the discriminative value of NT-pro-BNP is most pronounced in patients with GFR > or =90 ml/min/1.73 m(2) and has no prognostic value in patients with GFR <30 ml/min/1.73 m(2).     

Association between retinol-binding protein and renal function among Asian subjects with type 2 diabetes mellitus: a cross-sectional study

Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m2 (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A- controls with an eGFR > 60 ml/min per 1.73 m2, Group B - controls with an eGFR < 60 ml/min per 1.73 m2, Group C- T2DM subjects with an eGFR > 60 ml/min per 1.73 m2, and Group D - T2DM subjects with an eGFR < 60 ml/ min per 1.73 m2. In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m2 than in subjects with an eGFR > 60 ml/min per 1.73 m2. However, the difference was only significant between the control groups (p < 0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p < 0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM.     

Effect of Beta-blockade and ACE Inhibition on B-type Natriuretic Peptides in Stable Patients with Systolic Heart Failure

INTRODUCTION: The long-term effect of beta-blockade on the plasma levels of natriuretic peptides BNP and its N-terminal counterpart, NT-proBNP, as risk markers in heart failure (HF) is obscure. METHODS: Stable systolic HF patients from the CARMEN study were divided in groups matching their randomised treatment allocation: Carvedilol, enalapril or carvedilol+enalapril. Changes in BNP and NT-proBNP from baseline to 6 months maintenance visit were evaluated in each treatment arm. Furthermore, the prognostic value of BNP and NT-proBNP during monotherapy with carvedilol was assessed with univariate Cox proportional hazards models using a combined endpoint of all cause mortality and cardiovascular hospitalisation. RESULTS: NT-proBNP and BNP were significantly reduced after six months treatment with enalapril (NT-proBNP 1,303 to 857 pg/ml (P < 0.001), BNP 119 to 85 pg/ml (P < 0.001)) or carvedilol+enalapril (NT-proBNP 1,223 to 953 pg/ml (P = 0.003), BNP 117 to 93 pg/ml (P = 0.01)). In contrast, no change was observed in the carvedilol group (NT-proBNP 907 to 1,082 pg/ml (P = 0.06), BNP 114 to 130 pg/ml (P = 0.15). The prognostic value of NT-proBNP and BNP was maintained in the carvedilol group (NT-proBNP HR 1.018 95% CI (1.005-1.032), BNP 1.171 (1.088-1.260)). CONCLUSION: Treatment of HF patients with carvedilol alone does not reduce levels of natriuretic peptides, but treatment with enalapril does. Both BNP and NT-proBNP predict death and hospitalisation in HF patients treated with carvedilol for six months. The clinical implication of our results is that NT-proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic HF patients receiving carvedilol without ACE inhibition.     

Hemoglobin Decline in Children with Chronic Kidney Disease: Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population.Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration.Results: Of the 340 patients studied, the mean age was 11 ± 4 yr, the mean glomerular filtration rate was 42 ± 14 ml/min per 1.73 m², and the mean hemoglobin was 12.5 ± 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval −0.2 to −0.5) for every 5-ml/min per 1.73 m² decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m², the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m² decrease in glomerular filtration rate.Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m². Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals.The adverse health effects of anemia in adult and pediatric patients with chronic kidney disease (CKD) are both common and profound. Anemia has been associated with increased mortality, limitations in physical activity, and adverse effects on quality of life. Among children in the 2005 End Stage Renal Disease Clinical Performance Measures Project, 95% of 1598 prevalent pediatric patients with ESRD were anemic; 95% of patients who were receiving hemodialysis and 94% of patients who were receiving peritoneal dialysis were prescribed erythropoiesis-stimulating agents (ESA) (1). A lower prevalence of anemia is observed at earlier stages of CKD in pediatric patients. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) stages CKD as follows: Stage 1, evidence of kidney damage with normal or increased GFR; stage 2, GFR 60 to 89 ml/min per 1.73 m²; stage 3, GFR 30 to 59 ml/min per 1.73 m²; stage 4, GFR 15 to 29 ml/min per 1.73 m²; stage 5, GFR <15 ml/min per 1.73 m² or on dialysis (2). In a recent single-center, cross-sectional study of 366 children and adolescents with CKD, approximately 30% of patients with stages 1 and 2 CKD reported prevalent anemia, defined as hemoglobin <12 mg/dl or medical treatment for anemia, whereas 66% of patients with stage 3 and 93% of patients with stages 4 and 5 CKD were anemic. GFR was estimated from serum cystatin C in this study (3).The lower prevalence of anemia in patients with earlier stages of CKD suggests an association between hemoglobin and GFR. In adults, hemoglobin has been reported to decline below a GFR threshold of 40 to 60 ml/min per 1.73 m² as measured by the Modification of Diet in Renal Disease (MDRD) or Cockcroft-Gault equation (4,5). This association, including the existence of a “GFR threshold,” has not been clearly described in children. This study aimed to define more clearly the relationship between hemoglobin and GFR in the pediatric CKD population. To accomplish this, we used the relatively large sample size and precise measurement of GFR offered by the Chronic Kidney Disease in Children Prospective Cohort Study (CKiD).     

Comparison of coronary atherosclerotic volume in patients with glomerular filtration rates < or = 60 versus > 60 ml/min/1.73 m(2): a meta-analysis of intravascular ultrasound studies

The relation between glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) and the extent and progression of coronary atherosclerosis in 989 subjects with coronary artery disease was investigated. Despite being older, more likely to be women, and having a history of hypertension, diabetes, and bypass surgery, total atheroma volume and percent atheroma volume in subjects with a low GFR did not differ from subjects with a GFR >60 ml/kg/min. Similarly, there was no difference in progression rates of total atheroma volume and percent atheroma volume in patients with GFRs lower and higher than 60 ml/min/1.73 m(2) in response to a high rate of use of established preventive therapies. In conclusion, findings suggest that the increased incidence of clinical events in patients with impaired renal function may result from factors other than atherosclerotic burden.     

Influence de la fonction rénale sur la pertinence diagnostique du BNP chez l’insuffisant cardiaque âgé

Aim of the study

BNP levels are accurate in the diagnosis of heart failure and useful in clinical practice. Relationship between BNP, heart failure (HF) and renal function are little known in the elderly. Renal function influence the optimal cut point of BNP in patients with a Glomerular Filtration Rate (eGFR) lesser than 60 ml/min/1.73 m².

Methodology

A total of 71 patients (mean age = 85 years) were admitted in a Cardiogeriatric Unit. We noted several parameters, age, gender, the presence or the absence of Systolic Heart Failure (clinical history and physical examination), the echographic measure of the left ventricular ejection fraction, the eGFR value calculated by simplified MDRD formula and the BNP value. We divided these patients into six groups according the presence of HF and eGFR value higher than 60ml/min/1.73m²,or between 30 and 60 or between 15 and 30.

Results

Our results show that the BNP value is higher in all the three groups of patients with Heart Failure with or without diminution of the eGFR: for example, 1220 pg/ml in the presence of HF versus 788 pg/ml in the absence of HF in the two groups with the eGFR is calculated between 15 and 30 ml/min/1.73m².

Conclusion

BNP is a helpful tool in clinical practice for the diagnosis of Systolic Heart Failure in the presence of renal impairment in the elderly with a higher biomarker cut point.     

Renal function after autologous bone marrow transplantation in children: a long-term prospective study

We measured glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and the concentrating capacity of the kidneys in children after autologous BMT. Twenty-six patients had received TBI in their conditioning regimen and 14 patients had received chemotherapy only. Median follow-up was 10 years. Mean GFR before BMT was close to normal in both groups. Mean GFR decreased from 124 [CI 114,134] ml/min/1.73 m(2) before BMT to 99 [CI 82,115] ml/min/1.73 m(2) 6 months after BMT in the + TBI group (P < 0.001). There was no significant change in the -TBI group. Mean ERPF before BMT was high: 1110 [95% CI 830,1390] ml/min/1.73 m(2) in the + TBI group and 910 [CI 570,1250] ml/min/1.73 m(2) in the - TBI group. Six months after BMT, there was a tendency to a decrease in ERPF in the +TBI group, to 760 [CI 580,940] ml/min/1.73 m(2) (P = 0.064). After this initial decrease, GFR and ERPF remained essentially unchanged in both groups. The mean concentrating capacity of the kidneys was normal before and after BMT. In seven patients chronic renal impairment developed after BMT (GFR <70 ml/min/1.73 m(2)). All had received TBI. They had also received more nephrotoxic antibiotics than the other patients. We conclude that TBI was the principal cause of deterioration of renal function after BMT, possibly by limiting compensatory hyperperfusion and resulting in a fall in GFR. Antibiotic treatment may have contributed.     

Long-term renal effects of diltiazem in essential hypertension

Eighteen hypertensive patients underwent short-term (8 weeks) and long-term (6 months) assessment of renal function and body fluid composition following diltiazem monotherapy (240 to 480 mg/day). Diltiazem monotherapy effectively lowered blood pressure in 60% of patients at 8 weeks. In 12 of the 18 patients continued on diltiazem monotherapy for 6 months, good control of blood pressure was sustained. Glomerular filtration rate, effective renal plasma flow, filtration fraction, and renal vascular resistance were unchanged throughout the protocol period. In individuals with pretreatment glomerular filtration rates less than or equal to 80 ml/min/1.73m2, diltiazem monotherapy showed both short-term and long-term improvement in glomerular filtration rate (62%) and effective renal plasma flow (34%). Filtration fraction was unchanged, suggesting that the changes in glomerular filtration rate might be related to the attenuated intrarenal effects of angiotensin II and/or norepinephrine. No long-term effect was seen on salt and water excretion or body fluid composition.