Natriuretic peptides, brain natriuretic peptide (BNP), and N-terminal probrain natriuretic peptide (NT-proBNP) are mainly known as diagnostic markers for heart failure with high diagnostic and prognostic values in the general population. In patients who are undergoing hemodialysis (HD), changes in NT-proBNP can be related to noncardiac problems such as fluid overload, inflammation, or malnutrition and can also be influenced by the dialysis characteristics. The current review aimed to summarize findings from studies on the association between NT-proBNP and malnutrition in HD patients. Articles published after 2009 and over a ten-year period were considered for inclusion. We first briefly discuss the traditional functions of NT-proBNP, and after, we describe the functions of this prohormone by focusing on its relation with protein energy wasting (PEW) in HD patients. Mechanisms that could explain these relationships were also discussed. Overall, 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects were taken into account. NT-proBNP levels correlated with several factors described in the 4 categories of markers indicative of PEW (body mass and composition, muscle mass, biochemical criteria, and dietary intakes) and/or were associated with PEW. Interactions between several parameters could be involved in the association between NT-proBNP and malnutrition with a strong role of weight status. NT-proBNP is elevated in HD patients and is associated with malnutrition. Nevertheless, the prognostic value of NT-proBNP on nutritional status should be evaluated.
Uremic malnutrition, also called malnutrition inflammation complex syndrome or protein energy wasting, corresponding to a decrease in energy and body protein, is a common problem in patients with end-stage renal disease (ESRD) undergoing HD and has been consistently associated with mortality in different populations [
Brain natriuretic peptide (BNP) is synthesized mainly in the heart as a proBNP that is further cleaved into bioactive BNP and biologically inactive NT-proBNP [
The current review aimed to summarize findings from studies on the association between NT-proBNP and malnutrition in HD patients.
For this review, we reviewed the literature using PubMed, Medline, and Scopus with the following search terms: N-terminal probrain natriuretic peptide (NT-proBNP), nutritional status, malnutrition, and hemodialysis (HD) in humans. We also searched in the selected articles and took into account some of the relevant references cited by the authors. Mechanisms that could explain these relationships were also discussed while also taking the results of some animal studies into account.
Articles published after 2009 and over a ten-year period, in adults (>18 year of age), were considered for inclusion.
We first briefly discuss the characteristics and traditional functions of NT-proBNP, and after, we describe the functions of this prohormone by focusing on its relation with protein energy wasting (PEW) in patients undergoing maintenance HD.
During the period taken into account in this review, we found 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects [
Summary of studies on relationships between NT-proBNP and protein energy wasting in maintenance hemodialysis.
Authors | Country | Number of HD subjects | Study design |
NT-proBNP levels |
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Guo et al. [ |
Sweden |
|
Cross-sectional study and longitudinal study |
Values (median (IQR)): 11,609 (4,581–35,000) with wasting signs (SGA > 1) 5,671 (1,909–17,141) pg/ml in those without |
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Bednarek-Skublewska et al. [ |
Poland |
|
Cross-sectional study |
Values (range): 403–35,000 pg/ml |
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Lee et al. [ |
Korea |
|
Cross-sectional study |
Values (median (IQR)): 4,342 (1,582–22,304) pg/ml in well-nourished 24,807 (11,435–44,127) pg/ml in malnourished |
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Snaedal et al. [ |
Sweden |
|
Longitudinal study |
Values (median (IQR)): 8,946 (2,909–26,571) pg/mL 12,932 (5,658–35,001) pg/mL with PEW (SGA > 1) 6,092 (2,248–17,670) pg/mL without PEW |
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Schwermer et al. [ |
Poland |
|
Longitudinal study |
Values: (mean ± SD): 6,098 ± 19,659 |
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Ikeda et al. [ |
Japan |
|
Longitudinal study |
Values (median (range)): 2,910 (465–78,400) pg/ml |
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Ducros et al. [ |
Guadeloupe (France) |
|
Cross-sectional study |
Values (range): 125–33,144 pg/ml (median (IQR)): 6,243 (1833–18,721) pg/mL with PEW 2,132 (1,100–5,200) pg/mL without PEW |
BIA: bioimpedance analysis. %CGR: percentage creatinine generation rate. MIS: malnutrition-inflammation score. IQR: interquartile range. ISRNM: International Society of Renal Nutrition and Metabolism. PEW: protein energy wasting. SD: standard deviation. SGA; subjective global assessment.
The levels of the prohormone vary according to the population studied. NT-proBNP is cleared by the kidney and, in patients with CKD, especially those on HD, levels of NT-proBNP are usually increased as a consequence of increasing secretion and decreasing renal clearance [
Thus, elevated levels of the prohormone are often observed in HD patients without clinical evidence of cardiovascular disease. These high NT-proBNP levels in patients with renal dysfunction [
The influences of age, gender, body mass index (BMI), time of the dialysis session during the week, time of measurement of NT-proBNP before or after a hemodialysis session, dialysis characteristics, and membrane type have been reported [ In some studies, blood concentrations of NT-ProBNP were associated with hypervolemia or fluid overload [ Inflammation also influences NT-proBNP levels [
Studies on maintenance of HD patients have reported the association between NT-proBNP levels and malnutrition by subjective global assessment (SGA), malnutrition-inflammation score (MIS), or markers defined in the International Society of Renal Nutrition and Metabolism (ISRNM) nomenclature [
Globally, SGA is a tool that uses 5 components of a medical history (weight change, dietary intake, gastrointestinal symptoms, functional capacity, and disease and its relation to nutritional requirements) and 3 components of a brief physical examination (signs of fat and muscle wasting, nutrition-associated alterations in fluid balance) to assess nutritional status [
The practice guidelines and criteria for evaluating nutritional status in ESRD patients recommend the use of nomenclatures for PEW [
To study these relationships, we first focused on the relation between the main parameters described in the 4 categories of factors for PEW identification according to the ISRNM nomenclature, and after, we considered the relation with malnutrition status in each of the studies.
Lower BMI, body fat, and unintentional weight loss over time are included in this category of nutritional markers in the ISRNM nomenclature.
Assessment of nutritional status and especially evaluation of muscle mass is essential for the identification of patients at risk for the development of PEW [
Some biochemical indicators have been proposed for the diagnosis of PEW, and serum albumin, serum prealbumin (transthyretin), and cholesterol have been studied as nutritional markers in CKD patients [
In the ISRNM nomenclature, low dietary intake was considered in the presence of unintentional low dietary protein intake <0.8 g/kg/day for at least 2 months for dialysis patients or unintentional low dietary energy intake <25 kcal/kg/day for at least 2 months [
The 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects are summarized in Table
In 222 HD patients, the association between NT-proBNP, PEW, and inflammation was evaluated. NT-proBNP was analyzed in plasma by an immunometric assay. Patients presenting with an SGA score of 2–4 were defined as malnourished. A NT-proBNP level above 9,761 pg/ml was associated with PEW even following adjustment for age, dialysis vintage, inflammation, and Davies score [
In 97 HD patients, the relationship between serum level of NT-proBNP and nutritional status, inflammation, and hydration was investigated. NT-proBNP was measured by an immunoassay. The nutritional status was evaluated with specific markers including BMI, albumin, and nPCR. NT-proBNP was only moderately associated directly with hydration status but was extremely elevated in patients with intensive catabolism [
In 44 HD patients, nutritional status was assessed using subjective SGA and MIS. NT-proBNP was measured by immunoassay, malnutrition was accompanied by volume overload and associated with increased log NT-proBNP, and these levels were independently associated with increased left ventricular mass index [
A prospective study was performed in 211 HD patients to analyze NT-proBNP variability and the factors predicting this variability. Malnutrition was one of the studied factors. NT-proBNP was measured by an immunometric assay. Longitudinal changes in NT-proBNP were associated with changes in nutritional status. Patients with wasting and patients with congestive heart failure had significantly higher NT-proBNP levels than patients without these conditions [
A study aiming to establish the usefulness of NT-proBNP for hydration assessment and the relation of NT-proBNP with the nutritional state and prognosis of survival was conducted in 321 HD patients. NT-proBNP was measured by immunoassay. Bioimpedance analysis was used. Patients were classified according to quartiles of NT-proBNP. NT-proBNP correlated negatively with practically all nutritional indices including serum albumin, cholesterol, and BMI. The highest albumin level was present in Q1 (4.10 ± 0.63/3.99 ± 0.51/3.90 ± 0.62/3.97 ± 0.78 g/dl;
In a prospective observational study with one-year follow-up in a cohort of prevalent HD patients (
The association between PEW and NT-proBNP was evaluated in a cross-sectional study performed in 207 Afro-Caribbean HD patients. One component in each of the 4 categories for the wasting syndrome (according to the ISRNM nomenclature) was retained: serum albumin <38 g/L, BMI < 23 kg/m2, serum creatinine < 818
In some other studies, authors found associations between NT-proBNP and signs of wasting, but the investigation of these relations was not the main objects in these studies [
Several hypotheses have been proposed concerning the association between high NT-proBNP and PEW. A direct effect of PEW on the level of NT-proBNP by affecting ventricular remodeling in HD patients has been suggested [ Complex interactions between NT-proBNP, malnutrition, inflammation, and fluid overload have been reported in HD patients [ Several parameters among 4 established categories (body mass and composition, muscle mass, biochemical criteria, and dietary intakes) for the definition of PEW according to ISRNM are separately associated with NT-proBNP. Interaction between some of these parameters could be involved in the association between NT-proBNP and malnutrition with a strong role of weight status [ Other hypothesis, suggested in patients without CKD, might be involved in HD patients.
Adipose tissue could also play an important role. It has been shown that NP display a lipolytic effect in adipose tissue [
In summary, the data suggest that NT-proBNP correlates with the indices of protein energy wasting and malnutrition. Therefore, this marker seems to be useful in the evaluation of nutritional status in hemodialysis. However, limitations in most of the above studies include the small sample size, the isolated measurements of the biomarker, the lack of precision regarding the time of NT-proBNP measurement in some studies, and the potential biases related to the methods used for PEW assessment. Factors indicating the presence of PEW can also be induced by inflammatory processes. Thus, the clinical context should be taken into account for the interpretation of elevated NT-proBNP levels. Since high NT-proBNP is primarily a marker of cardiac dysfunction, the increased levels of the prohormone must draw attention to cardiac function but also to nutritional status. Nevertheless, we must highlight the need to evaluate the prognostic value of NT-proBNP for malnutrition in hemodialysis in further studies.
Bioimpedance analysis
Body mass index
Brain natriuretic peptide
Chronic kidney disease
End-stage renal disease
Hemodialysis
High-sensitive C-reactive protein
Interdialytic weight gain
International Society of Renal Nutrition and Metabolism
Malnutrition-inflammation score
Natriuretic peptides
Normalized protein catabolic rate
N-terminal probrain natriuretic peptide
Percentage creatinine generation rate
Protein energy wasting
Subjective global assessment.
The authors declare no conflicts of interest.
The authors would like to acknowledge Mrs Jeanne Arjounin (Head of the library at the University Hospital Center, Guadeloupe) and Mr Peter Tucker (Medical Translator/Editor for medical authors at University Hospitals in France and Belgium) for their support.