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Article

NT-proBNP Levels in Hemodialysis Patients: Unrelated to Interdialytic Weight Gain, Limited in Detecting Left Ventricular Systolic Dysfunction, but May Identify Atrial Fibrillation

by
Maria Divani
,
Katerina Katsanaki
,
Maria Tziastoudi
,
Panagiota Makri
,
Christina Poulianiti
,
Evangelos Lykotsetas
,
Andriani Balatsouka
,
Ioannis Stefanidis
and
Theodoros Eleftheriadis
*
Department of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, Greece
*
Author to whom correspondence should be addressed.
Kidney Dial. 2026, 6(2), 42; https://doi.org/10.3390/kidneydial6020042
Submission received: 21 March 2026 / Revised: 1 June 2026 / Accepted: 8 June 2026 / Published: 9 June 2026
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Abstract

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is released in response to increased cardiac wall stress and is used as a biomarker for volume overload and heart failure (HF). It is also elevated in atrial fibrillation (AF) and inflammation. However, in hemodialysis (HD) patients, its interpretation is complicated by reduced renal clearance, large fluid shifts between dialysis sessions, and chronic inflammation. Methods: In 123 HD patients, we examined the relationship between NT-proBNP and interdialytic weight gain, HF with preserved ejection fraction (HFpEF), left ventricular systolic dysfunction (LVSD), and AF, as well as the impact of inflammation. Clinical characteristics, laboratory data, and echocardiography (within three months) were evaluated, while serum NT-proBNP and calprotectin levels were measured by ELISA. Results: NT-proBNP showed no association with interdialytic weight gain and did not identify HFpEF. Inflammatory markers (C-reactive protein and calprotectin) correlated positively with NT-proBNP. Multivariable analysis demonstrated that LVSD, AF, and inflammation remained independent predictors of NT-proBNP levels. Although NT-proBNP levels were higher in LVSD, its diagnostic performance was poor (AUC 0.627). In contrast, NT-proBNP was significantly elevated in patients with AF and showed good diagnostic performance (AUC 0.801). Conclusions: In HD patients, NT-proBNP is not correlated with interdialytic weight gain, performs poorly as a marker of LVSD, but may serve as a useful marker of AF.

Graphical Abstract

1. Introduction

N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) is produced by cardiomyocytes in response to myocardial stretch, and patients with suspected heart failure (HF) should undergo a serum NT-proBNP test. Patients with elevated serum NT-proBNP levels should undergo an echocardiogram and cardiology evaluation. This test also aids in diagnosing acute decompensated HF and volume overload [1,2].
In addition to HF, NT-proBNP levels are elevated in patients with atrial fibrillation (AF). In a large cohort of overweight and obese patients, elevated NT-proBNP was associated with left atrium volume enlargement and dysfunction, suggesting its potential for predicting and preventing AF [3]. In patients with newly diagnosed AF, atrial cardiomyopathy, assessed by left atrial size, was present in 69% of 2810 patients, and NT-proBNP was elevated in 56% [4]. In patients with a history of AF, continuous rhythm monitoring over 1 year showed that high serum NT-proBNP levels were associated with increased AF burden and/or episodes lasting more than 24 h [5]. Finally, a large retrospective study of 155,345 individuals who underwent NT-proBNP testing concluded that NT-proBNP is elevated in patients with AF. Consequently, NT-proBNP identifies HF more accurately in individuals without AF than those with AF [6].
Importantly, the presence of chronic kidney disease (CKD) introduces additional limitations to the clinical interpretation of NT-proBNP levels. Although numerous studies confirmed that elevated NT-proBNP predicts cardiovascular events and mortality in hemodialysis (HD) patients [7,8,9,10,11,12,13,14], various non-HF-related factors may affect its levels. First, decreased renal clearance of NT-proBNP results in a significant elevation of its levels in patients with CKD [15,16]. Additionally, fluid overload is common in this population, often due to interdialytic weight gain or imprecise dry-weight determination, and can also lead to elevated NT-proBNP levels [17,18,19,20]. Notably, in one study, increased NT-proBNP levels were associated with fluid overload rather than with cardiac ejection fraction, left ventricular end-diastolic and systolic dimensions, intraventricular septal and posterior ventricular wall thickness, and left atrial diameter [21]. Consistent with the role of decreased renal function and fluid overload in increased NT-proBNP levels is the finding that, in HD patients, the greater the residual diuresis, the lower the serum NT-proBNP levels [22,23]. The same has been observed in patients undergoing peritoneal dialysis [24]. Furthermore, in HD patients, the prevalence of AF is higher than in the general population and is associated with increased mortality [25]. Implantable loop recorders for continuous cardiac rhythm monitoring in 66 HD patients revealed incident AF episodes in 41% over a 6-month follow-up period [26]. As in the general population, AF in HD is associated with elevated NT-proBNP or BNP levels [20,27]. Finally, chronic low-grade inflammation is prevalent in HD patients and is associated with high NT-proBNP levels [13,28,29,30]. This association has also been observed in patients without CKD [31,32].
In this complex landscape, we evaluated whether fluid status, assessed by interdialytic weight gain and residual diuresis, and inflammation, assessed by serum C-reactive protein (CRP) and calprotectin, affect serum NT-proBNP levels in HD patients. Our main aim was to investigate whether NT-proBNP levels could identify patients with HF with preserved ejection fraction (HFpEF), left ventricular systolic dysfunction (LVSD), or AF.

2. Materials and Methods

2.1. Patients

A total of 123 clinically stable HD patients were enrolled in the study. The mean age of the cohort was 66.00 ± 12.2 years; 87 were male, and 36 were female. The cause of end-stage kidney disease (ESKD) was diabetic nephropathy (n = 32), primary glomerulonephritis (n = 25), hypertension (n = 20), cardiorenal syndrome (n = 8), autosomal dominant polycystic kidney disease (n = 8), secondary focal segmental glomerulosclerosis (n = 6), vasculitis (n = 4), obstructive nephropathy (n = 2), analgesic nephropathy (n = 2), and unknown causes (n = 16).
Forty-six patients had diabetes mellitus. Forty-four patients had a history of coronary heart disease (CHD), confirmed by coronary artery angiography performed for angina symptoms or after a myocardial infarction. Thirty-four patients had a history of AF, defined as a documented history of paroxysmal, persistent, or permanent atrial fibrillation based on medical records and/or electrocardiographic findings, with most receiving anticoagulant therapy, including acenocoumarol (n = 9), low-molecular-weight heparin (n = 9), or half-dose apixaban (n = 4). Eighty-two individuals were on statin therapy, and most were taking antihypertensive medications. Attending nephrologists determined the use of phosphate binders, vitamin D analogs, and calcimimetics. All patients had been on HD for at least six months before inclusion. They underwent standard HD sessions with polysulfone dialyzers and bicarbonate-based dialysate containing calcium at 1.25 or 1.5 mmol/L. Each HD session lasted 4 h and was performed 3 times per week. Residual diuresis over 500 mL/day was present in 30 patients. Fifty-two patients underwent HD through a central venous catheter (CVC).
Patients presenting with dyspnea upon arrival at the HD unit were excluded from participation. Further exclusion criteria included active infection, autoimmune disease, malignancy, liver pathology, or administration of cytotoxic, immunosuppressive, or corticosteroid therapy within the previous six months. All eligible patients attending the dialysis unit during the study period who met the predefined inclusion and exclusion criteria were consecutively enrolled. No formal a priori sample size calculation was performed, as this was an exploratory observational study that included all eligible patients during the study period. However, a post hoc power analysis was conducted for the main findings of the study.
All patients underwent transthoracic echocardiography within 3 months of study enrollment. In accordance with contemporary heart failure guidelines [1,2], left ventricular systolic dysfunction (LVSD) was defined as reduced left ventricular systolic function with left ventricular ejection fraction (LVEF) < 50%, thereby including patients with HF with mildly reduced ejection fraction (HFmrEF; LVEF 41–49%) and reduced ejection fraction (HFrEF; LVEF ≤ 40%). Heart failure with preserved ejection fraction (HFpEF) was defined as LVEF ≥ 50% in the presence of echocardiographic evidence of diastolic dysfunction. We assessed LVSD rather than HFmrEF and HFrEF separately due to the small number of patients enrolled in the study. Based on echocardiographic findings, 37 patients were classified as having HFpEF, and 30 as having LVSD. Patients exhibiting tachycardia (heart rate > 100 bpm) or bradycardia (heart rate < 50 bpm), as well as individuals with severe mitral or aortic valve disease (regurgitation or stenosis), which could confound the assessment of ejection fraction, were excluded from the study.
Additional clinical and demographic features are presented in Table 1.
A control group of 22 healthy individuals (mean age 65.27 ± 6.17 years; 14 males, 8 females) was included after a thorough review of medical records and physical examination.
Written informed consent was obtained from all study participants. The study protocol was approved by the Ethics Committee of the Faculty of Medicine, University of Thessaly, Larissa.

2.2. Methods

Blood samples were obtained at the start of the second hemodialysis session of the week, and serum was stored at –80 °C.
Serum NT-proBNP concentrations were measured using the Human N-terminal pro-B-type natriuretic peptide (NT-proBNP) ELISA kit (Cusabio, Wuhan, China), which has a sensitivity of 0.216 ng/mL. Serum calprotectin was measured using the Calprotectin Human ELISA Kit (Hycult Biotech, Uden, The Netherlands) with a sensitivity of 1.6 ng/mL.
All other parameters were recorded as part of routine laboratory assessments performed concurrently with serum collection.

2.3. Statistical Analysis

Statistical analyses and graphical visualizations were performed using IBM SPSS Statistics version 29 (IBM Corp., Armonk, NY, USA), JASP version 0.95.4 (University of Amsterdam, Amsterdam, The Netherlands), and MedCalc free online statistical calculators version 23.5.9 (MedCalc Software Ltd., Ostend, Belgium). The distribution of variables was evaluated with the one-sample Kolmogorov–Smirnov test. Since serum NT-proBNP, CRP, and calprotectin levels were not normally distributed, non-parametric methods were used. Group comparisons were conducted with the Mann–Whitney U test, and data are shown as median (interquartile range). Correlations between continuous variables were analyzed using Spearman’s rank correlation coefficient. The relationship between NT-proBNP levels and variables correlated with them, or with conditions in which NT-proBNP levels differed significantly, was examined using multivariable linear regression analysis. Multicollinearity among independent variables was checked via Variance Inflation Factors (VIFs), with values > 5 indicating significant multicollinearity and values < 2.5 indicating minimal multicollinearity. Associations between categorical variables were tested with the Chi-square test. Receiver operating characteristic (ROC) curve analysis was performed, and the optimal cut-off points were determined by selecting the point that maximized Youden’s Index (J = Sensitivity + Specificity − 1). A post hoc power analysis was conducted for the main findings of the ROC curve analysis. When needed, comparisons of ROC curves were performed using the DeLong test. A p-value of <0.05 was considered statistically significant.
Raw data of the study are provided as Supplementary Material in Table S1.

3. Results

3.1. NT-proBNP Levels in HD Patients and Healthy Subjects

Serum NT-proBNP levels were markedly elevated in HD patients compared with healthy individuals. Healthy subjects had levels of 191.90 (179.20–1047.18) pg/mL, whereas HD patients showed levels of 1744.80 (1259.20–2755.80) pg/mL (p < 0.001) (Figure 1).
Interestingly, among HD patients, serum NT-proBNP levels showed no significant correlations with age (Rho 0.088, p = 0.331), duration of HD treatment (Rho 0.080, p = 0.382), urea reduction ratio (Rho −0.076, p = 0.403), body mass index (Rho 0.016, p = 0.859), albumin (Rho −0.029, p = 0.753), or intact parathyroid hormone (Rho 0.024, p = 0.796). Although a trend was observed, serum NT-proBNP concentrations did not differ significantly between females (2006.80 [633.08–2920.40] pg/mL) and males (1582.50 [1245.25–1903.85] pg/mL) (p = 0.067). The associations of NT-proBNP levels with the evaluated factors, as shown in Table 1, are presented in Table 2.
Among all the factors evaluated, serum NT-proBNP levels were correlated with white blood cell count, neutrophil count, cholesterol, triglycerides, calprotectin, and CRP. Additionally, NT-proBNP levels differed significantly among patients with or without LVSD, AF, and CRP > 1 mg/dL (Table 2). Multivariate linear regression analysis confirmed that LVSD, AF, neutrophils, CRP, and calprotectin independently influence serum NT-proBNP levels (Table 3).
Because neutrophils constitute a major component of the total white blood cell count, including both variables introduced structural multicollinearity. Therefore, the neutrophil count was retained as the more specific inflammatory marker. All VIF values were below 2.5, indicating minimal multicollinearity. The reversal in the direction of association between calprotectin and NT-proBNP in univariate (Rho 0.234) and multivariable (B −0.432) analyses likely reflects suppression/confounding effects rather than multicollinearity, as VIF values are low.

3.2. NT-proBNP Levels, Interdialytic Weight Gain, and Residual Diuresis in HD Patients

In HD patients, interdialytic weight gain, whether expressed as an absolute volume or as a percentage of dry weight, showed no correlation with serum NT-proBNP levels (Rho −0.17, p = 0.855 and Rho 0.005, p = 0.954, respectively).
As expected, interdialytic weight gain, expressed either as absolute volume (Rho −0.298, p < 0.001) or as a percentage of dry weight (Rho −0.330, p < 0.001), demonstrated a negative correlation with residual diuresis. Serum NT-proBNP levels did not correlate with residual urine output (Rho −0.14, p = 0.879). Using a daily urine output threshold of 500 mL, NT-proBNP levels were 1946.60 (1256.50–2726.65) pg/mL in patients producing less than 500 mL per day and 1720.00 (1411.40–3086.60) pg/mL in those producing more than 500 mL per day (p = 0.860) (Figure 2A).
Receiver operating characteristic (ROC) curve analysis showed that serum NT-proBNP does not reliably distinguish patients with residual diuresis exceeding 500 mL/day. The area under the curve (AUC) was 0.490 (95% CI 0.384–0.597; p = 0.861), indicating no predictive value (Figure 2B).

3.3. NT-proBNP Levels and Heart Failure in HD Patients

Serum NT-proBNP levels did not differ between HD patients with HFpEF, and those without heart failure. Levels were 1698.20 (1367.90–2741.60) pg/mL in the HFpEF group and 1679.60 (1206.70–2714.50) pg/mL in patients without HF (p = 0.564).
In contrast, NT-proBNP levels were significantly higher in HD patients with LVSD compared to those without HF. Levels were 2244.80 (1732.20–2866.60) pg/mL in the LVSD group and 1679.60 (1206.70–2714.40) pg/mL in patients without HF (p = 0.046).
Similarly, NT-proBNP levels were significantly elevated in HD patients with LVSD compared with those without LVSD (i.e., those with HFpEF or no HF). Levels were 2244.80 (1732.20–2866.60) pg/mL versus 1688.80 (1222.70–2725.90) pg/mL, respectively (p = 0.037) (Figure 3A).
ROC curve analysis indicated that serum NT-proBNP has limited diagnostic utility for detecting LVSD in HD patients. The AUC was 0.627 (95% CI 0.510–0.744; p = 0.034). At the optimal cut-off of 1719 pg/mL, sensitivity was 80% (95% CI 62.69–90.49) and specificity was only 54.84% (95% CI 44.73–64.56) (Figure 3B). However, a post hoc power analysis indicated limited statistical power (0.557), suggesting that this finding should be interpreted with caution and confirmed in larger cohorts.
A strong association was observed between LVSD and a history of coronary heart disease (CHD) (Pearson χ2 = 33.78, p < 0.001). However, serum NT-proBNP concentrations did not differ significantly between patients with and without CHD. Median levels were 2102.90 (1308.35–2918.60) pg/mL in HD patients with CHD and 1696 (1241.80–2572.80) pg/mL in those without CHD (p = 0.160).
Notably, HD via a CVC rather than an arteriovenous fistula was associated with LVSD (Pearson’s χ2 = 3.962, p = 0.047). However, NT-proBNP levels did not differ between patients with or without CVC (1819.5 [1201.2–2755.8] pg/mL vs. 1698.2 [1413.6–2747.95] pg/mL, p = 0.338). No association was detected between CVC use and CHD (Pearson’s χ2 = 0.052, p = 0.819).

3.4. NT-proBNP Levels and Atrial Fibrillation in HD Patients

NT-proBNP levels were markedly elevated in HD patients with a documented history of atrial fibrillation (AF) compared to those without AF. Patients with a history of AF had levels of 2763.70 (2105.60–4172.75) pg/mL, whereas those without AF had levels of 1674.60 (1125.70–2102.90) pg/mL (p < 0.001) (Figure 4A).
ROC curve analysis showed that serum NT-proBNP provides good diagnostic accuracy for detecting a positive history of AF in HD patients. The AUC was 0.801 (95% CI 0.714–0.888; p < 0.001). At an optimal cut-off of 2530 pg/mL, sensitivity was 70.59% (95% CI 53.83–83.17), and specificity was 84.27% (95% CI 75.31–90.39) (Figure 4B). Post hoc power analysis demonstrated excellent statistical power (>0.999), further supporting the robustness of this finding. No significant association was found between LVSD and a history of AF (Pearson χ2 = 0.642, p = 0.423). Also, no significant association was observed between a history of AF and CHD (Pearson χ2 = 0.597, p = 0.440). Notably, HD via a CVC rather than an arteriovenous fistula was not associated with AF (Pearson’s χ2 = 2.190, p = 0.130).

3.5. NT-proBNP Levels and Inflammation in HD Patients

Serum NT-proBNP levels were positively correlated with neutrophil count (Rho 0.359, p < 0.001), CRP levels (Rho 0.297, p < 0.001), and serum calprotectin concentration (Rho 0.234, p = 0.009). Notably, the emerging inflammatory marker calprotectin correlated positively with white blood cell count (Rho 0.228, p = 0.012), neutrophils (Rho 0.423, p < 0.001), and CRP (Rho 0.249, p = 0.006). Interestingly, serum CRP levels did not differ significantly between HD patients with or without LVSD (1.06 [0.84–1.61] mg/dL vs. 1.27 [0.81–1.59] mg/dL, p = 0.871), with or without AF (1.23 [0.89–1.60] mg/dL vs. 1.21 [0.82–1.53] mg/dL, p = 0.320), or with or without CHD (1.02 [0.78–1.59] mg/dL vs. 1.30 [0.83–1.60] mg/dL, p = 0.397). Moreover, CRP levels were not correlated with interdialytic weight gain (Rho 0.054, p = 0.555) or residual diuresis (Rho −0.034, p = 0.713). Also, CRP levels did not differ between patients dialyzed via a CVC or an arteriovenous fistula (1.3 [0.838–1.828] mg/dL vs. 0.950 [0.805–1.525] mg/dL, p = 0.082).
Using a serum CRP cut-off of 1 mg/dL to identify inflammation in HD patients, those with CRP levels below 1 mg/dL had lower NT-proBNP levels (1679.60 [1035.90–2411.35] pg/mL) compared to patients with CRP levels above 1 mg/dL (2006.80 [1373.40–3433.60] pg/mL, p = 0.011) (Figure 5A).
ROC curve analysis showed that serum NT-proBNP has limited capacity to distinguish patients with CRP levels above 1 mg/dL. The AUC was 0.634 (95% CI 0.536–0.732; p = 0.007). At the optimal cut-off of 1740 pg/mL, sensitivity was 62.69% (95% CI 50.72–73.28) and specificity was 64.29% (95% CI 51.19–75.54) (Figure 5B).
Notably, no significant association was detected between a serum CRP level above 1 mg/dL and LVSD (Pearson χ2 = 0.021, p = 0.886), a positive history of AF (Pearson χ2 = 1.985, p = 0.159), or CHD (Pearson χ2 = 0.552, p = 0.457).
Regarding calprotectin, serum levels were higher in patients with LVSD (2531.54 [1892.82–3820.65] ng/mL vs. 1903.23 [1259.40–2837.40] ng/mL, p = 0.019) or AF (3143.98 [1759.81–4059.68] ng/mL vs. 1904.30 [1305.0–2610.65] ng/mL, p = 0.008). Serum calprotectin concentration did not differ between patients with CHD and those without (1904.23 [1214.09–3657.63] ng/mL vs. 2072.47 [1382.99–3064.15] ng/mL, p = 0.924). No correlation was observed between calprotectin and intradialytic weight gain (Rho −0.038, p = 0.675) or residual diuresis (Rho −0.106, p = 0.244). Also, calprotectin levels did not differ between patients dialyzed via a CVC or an arteriovenous fistula (1913.36 [1395.54–3582.32] ng/mL vs. 1948.92 [1290.30–2791.68] ng/mL, p = 0.346).
ROC curve analysis showed that serum NT-proBNP has limited ability to distinguish patients with calprotectin levels above the median (1943.52 ng/mL). The AUC was 0.601 (95% CI 0.536–0.732; p = 0.007). At the optimal cut-off of 1740 pg/mL, sensitivity was 62.69% (95% CI 50.72–73.28) and specificity was 64.29% (95% CI 0.499–0.702).
In addition, ROC curve analysis showed that calprotectin levels modestly identified patients with LVSD (AUC 0.643 [95% CI 0.535–0.751], p = 0.01) or AF (AUC 0.655 [95% CI 0.541–0.760], p = 0.008). The DeLong test showed that the discriminatory capacity of NT-proBNP levels did not differ from that of calprotectin levels for LVSD (AUC difference −0.016, p = 0.844), but NT-proBNP was superior for AF (AUC difference 0.146, p = 0.045).

4. Discussion

Serum NT-proBNP is recognized as a biomarker for chronic or decompensated HF in the general population [1,2]. In HD patients, although elevated NT-proBNP is associated with increased cardiovascular events and mortality [7,8,9,10,11,12,13,14], its usefulness as a biomarker is limited by various confounding factors common in this population.
The impact of impaired renal function on NT-proBNP concentrations should be considered when interpreting this biomarker in HD patients, as decreased renal clearance elevates serum NT-proBNP levels [15,16]. The importance of renal function as a confounding factor in interpreting NT-proBNP became apparent in a retrospective study of 1036 patients with CKD, including 103 receiving HD. BNP levels increased progressively as renal function declined. Moreover, although BNP showed positive associations with CHD, congestive HF, and AF in univariate analyses among patients with CKD stages 1–5, these associations lost statistical significance in patients with CKD stage 5 undergoing HD [16]. Accordingly, we found that serum NT-proBNP levels are markedly higher in HD patients than in healthy individuals. However, we did not detect an association between residual diuresis and NT-proBNP levels. The latter contradicts previous studies showing that the greater the residual diuresis, the lower the NT-proBNP levels [22,23], but this may be because, in HD patients, residual renal diuresis is associated with a very low glomerular filtration rate and is confounded by other factors present in this population.
Volume overload and fluid status assessment constitute additional important confounding factors influencing NT-proBNP levels in HD patients. Volume overload is common in HD patients and results from increased interdialytic weight gain or imprecise dry weight determination. We did not find a correlation between interdialytic weight gain, either as an absolute volume or as a percentage of dry weight, and serum NT-proBNP levels. Typically, residual diuresis helps maintain low interdialytic weight gain, and this relationship was observed in our patient cohort. However, as previously noted, residual diuresis did not affect NT-proBNP levels. These conflict with findings from various studies indicating that fluid overload in HD patients raises NT-proBNP levels [17,18,19,20]. Nonetheless, most of those studies assessed fluid status by measuring the extracellular-to-intracellular water ratio using bioelectrical impedance analysis. Although this method is more precise than clinical criteria, it is not widely used in clinical practice for determining the dry weight of HD patients. Certainly, increased interdialytic body weight indicates greater overhydration in patients, and the lack of association with NT-proBNP levels may reflect multiple confounding factors in this population. Conversely, our result might indicate that advanced methods, such as bioelectrical impedance analysis, for assessing body composition should be incorporated into routine clinical practice. However, this is not the case at present, and the currently available clinical trials have not demonstrated clinical benefits from modern volume management strategies guided by assistive technologies [33,34,35].
The association between inflammation and NT-proBNP has been consistently reported in both the general and HD populations. In a large cohort of older men followed for an average of 16.3 years, researchers found that new cases of HF were associated with NT-proBNP levels and with the inflammatory markers IL-6 and CRP. A correlation between inflammatory markers and NT-proBNP levels was noted [31]. Interestingly, a similar relationship between high-sensitivity CRP and NT-proBNP levels has also been observed in young, healthy adults [32]. The relationship between inflammation and BNP appears to be bidirectional. Exposure of cardiomyocytes to pro-inflammatory cytokines increases BNP synthesis [36]. Additionally, administering lipopolysaccharide to healthy volunteers elevates NT-proBNP levels [37]. On the other hand, exposure of macrophages to BNP increases both pro-inflammatory cytokines and the anti-inflammatory cytokine IL-10 [38]. Notably, chronic low-grade inflammation is prevalent in HD patients and is associated with high NT-proBNP levels [28,29,30]. In our patient, CRP correlated with serum NT-proBNP levels, and patients with CRP levels above 1 mg/mL had significantly higher NT-proBNP levels. However, ROC curve analysis revealed that NT-proBNP performs poorly as an indicator of inflammation in HD patients, with a statistically significant p-value but a relatively low AUC of 0.634. Our results are consistent with other studies and indicate that inflammation is a confounding factor when interpreting serum NT-proBNP levels in HD patients.
To further evaluate the role of inflammation, we also examined the association between NT-proBNP and the emerging inflammatory marker calprotectin. Calprotectin is an emerging inflammatory marker that reflects neutrophil activation [39]. It is elevated in HD patients and has been associated with increased overall and cardiovascular mortality [40,41,42]. We observed a positive correlation between serum calprotectin and white blood cell count, neutrophils, and CRP, supporting calprotectin as an inflammatory marker in HD patients. NT-proBNP levels were unable to discriminate patients with serum calprotectin levels above or below the median. However, caution is needed when interpreting this result because, unlike CRP, serum calprotectin is an emerging inflammatory marker without established upper limits in clinical practice, and the median may not be highly clinically relevant. The correlations between the inflammatory markers CRP and calprotectin and NT-proBNP levels, along with the modest capacity of calprotectin to discriminate patients with LVSD or AF, although not superior to that of NT-proBNP, indicate that inflammation is a confounding factor that limits the use of serum NT-proBNP levels as a marker in the HD population.
We next evaluated the diagnostic utility of NT-proBNP for detecting LVSD in HD patients. In response to myocardial stretch, ventricular myocytes produce BNP, while NT-proBNP, a more stable byproduct in the BNP synthesis pathway, has become an established biomarker for HF [1,43]. In our HD patients, serum NT-proBNP levels did not differ between those with HFpEF and those without HF. In patients with LVSD, NT-proBNP levels were found to be higher compared to those without heart failure or in the group that includes both patients with HFpEF and those without heart failure. However, ROC curve analysis revealed that NT-proBNP performs poorly as an indicator of LVSD in HD patients, with a statistically significant p-value but a relatively low AUC of 0.627. At the optimal cut-off level, its sensitivity was 80%, but the specificity was only 55%. In our cohort, NT-proBNP performs worse than in another study with outstanding discrimination (AUC 0.94) [30]. It also performs worse than in a study (AUC 0.859), which, however, assessed HFrEF (LVEF < 40%) and measured post-dialysis NT-proBNP levels [44]. As noted, our results on the discriminatory capacity of NT-proBNP to identify HD patients with LVSD should be interpreted with caution due to the limited statistical power. In addition, our study detected a strong association between LVSD and a history of CHD. However, serum NT-proBNP concentrations did not differ significantly between patients with and without CHD.
NT-proBNP appeared particularly limited in discriminating HD patients with HFpEF. A study included four longitudinal community-based cohorts comprising 22,756 participants with a median follow-up of 12 years, during which 633 developed incident HFpEF and 841 developed incident HFrEF, and found that NT-proBNP was more strongly associated with HFrEF than with HFpEF [45]. Thus, the cofounding factors present in HD patients may have contributed to the lack of difference in serum NT-proBNP levels between patients with HFpEF and those without HF observed in our study.
Atrial fibrillation is another major determinant of elevated NT-proBNP levels in HD patients. In HD patients, the prevalence of AF is higher than in the general population and is linked to increased mortality [25]. Similar to the general population [3,4,5,6], AF in HD patients is associated with elevated NT-proBNP or BNP levels [20,27]. In our HD patients, serum NT-proBNP levels were significantly higher in those with a history of AF than in those without. ROC curve analysis revealed that NT-proBNP performs well as an indicator of AF in HD patients, with a p-value < 0.001 and an AUC of 0.801. At the optimal cut-off value, sensitivity was 71%, and specificity was 84%. In our cohort, NT-proBNP performed better (AUC 0.801) than in another study (AUC 0.734), which, however, assessed BNP levels in relation to incident AF [27]. Notably, no significant association was found between AF and LVSD or CHD.
Our findings suggest that AF may be the cardiovascular condition most strongly associated with NT-proBNP elevation in HD patients. In addition to ventricular myocytes, atrial myocytes also produce BNP. This is supported by the fact that, in patients with AF, elevated NT-proBNP levels are associated with left atrial enlargement and dysfunction [3,4]. Notably, in patients with AF, BNP concentrations were significantly higher in blood drawn from the coronary sinus (atrial drainage) than in blood drawn from the anterior interventricular vein (ventricular drainage), and atrial BNP production decreased significantly after successful DC cardioversion of AF [46]. From a clinical perspective, the significance of our finding that NT-proBNP levels can indicate a history of AF lies in the potential to use NT-proBNP to predict and prevent new-onset AF, since AF is associated with increased mortality in the HD population [25]. Notably, paroxysmal AF recurrence is more common in HD patients, and even cardiac ablation therapy has a much lower success rate than in the general population [47]. Given that AF episodes occurred during or shortly after HD sessions, measures to reduce interdialytic weight gain, accurately determine patients’ dry weight, avoid high ultrafiltration rates and high potassium shifts, and improve dialysis adequacy may be beneficial [26,27,48].
We also investigated whether the type of vascular access influences NT-proBNP levels and cardiovascular status in HD patients. The adverse effects of arteriovenous fistulas, especially when access flow is high, on cardiac function in HD patients are well known [49]. Weeks after AVF creation, particularly when blood flow exceeds 600 mL/min, structural and functional cardiac changes occur, and NT-proBNP increases [50]. Therefore, we also evaluated whether HD through CVC has any beneficial effect on cardiac function or NT-proBNP levels. However, in our cohort, patients dialyzed via a CVC were less likely to have LVSD. This may reflect that patients with CVCs tend to be older and have more comorbidities, including cardiovascular disease [51,52,53]. NT-proBNP levels did not differ between patients with and without a CVC. Comorbidities and differences in AVF blood flow may account for this. Notably, HD through CVC was not associated with AF, and neither CRP nor calprotectin levels differed between patients dialyzed via a central venous catheter or an arteriovenous fistula.
Taken together, our findings indicate that the clinical utility of NT-proBNP varies depending on the cardiovascular condition being evaluated in HD patients. Overall, our study suggests that NT-proBNP may be a clinically useful biomarker for identifying AF in HD patients, whereas its utility for detecting LVSD appears more limited in this population. The weaker discriminative performance and lower statistical power observed for LVSD likely reflect multiple non-cardiac factors that influence NT-proBNP levels in HD patients, including impaired renal clearance, chronic inflammation, and volume fluctuations. Further studies with larger cohorts are warranted to better define the diagnostic role of NT-proBNP for systolic heart failure in this setting.
Because NT-proBNP is not a perfect biomarker for detecting cardiovascular disease, particularly in HD patients, emerging biomarkers are under investigation. For example, galectin-3 and soluble suppression of tumorigenicity-2 (sST2) are two promising biomarkers. Galectin-3 is a lectin that promotes cardiac remodeling and fibrosis by activating macrophages and fibroblasts. sST2 reflects myocardial stress and fibrosis-related signaling through the IL-33/ST2 pathway. These two biomarkers have been studied in the context of HF. Nevertheless, novel data link galectin-3 and sST2 to CHD and AF [54]. A meta-analysis has shown an association between galectin-3 and mortality, vascular stiffness, or LVSD in HD patients [55]. Importantly, sST2 appears to be less affected by renal impairment than NT-proBNP, potentially improving risk stratification in HD patients [56,57]. However, additional large prospective studies are required before their routine use in clinical practice.
Several limitations of the present study should be acknowledged when interpreting our findings. First, although we found an association between serum NT-proBNP levels and the prevalence of LVSD and predominantly AF, its cross-sectional design precludes causal inference. Longitudinal studies that measure NT-proBNP over time are necessary to clarify causal relationships and determine whether serum NT-proBNP acts as a marker of LVSD and AF in HD patients. To address this, we plan to conduct follow-up assessments within the current cohort, enroll additional patients, and include participants from multiple centers to validate the association between NT-proBNP and cardiovascular complications. Such studies will also help identify accurate NT-proBNP cut-off points for diagnosis. Second, we relied on patients’ medical records to determine whether they had CHD or AF, and the transthoracic echocardiography was performed within three months of blood sampling. As a result, some cases of asymptomatic CHD may have been missed, and without continuous monitoring, the number of patients experiencing episodes of AF may have been underestimated. However, HD patients visit the HD units three times a week, which facilitates early recognition of CHD symptoms and AF. Furthermore, our patients have regular cardiology assessments and transthoracic echocardiography. In addition, transthoracic echocardiography was performed within a maximum interval of 3 months from blood sampling, a relatively short timeframe unlikely to have significantly influenced the results. Finally, dry weight was determined using clinical criteria. More advanced methods, such as bioelectrical impedance analysis, inferior vena cava ultrasound, or lung ultrasound, could improve the accuracy of dry weight assessments. However, these techniques have not yet been widely adopted in clinical practice, and the currently available clinical trials have not demonstrated that volume management strategies guided by assistive technologies are superior to usual care in improving hard clinical outcomes [33,34,35].

5. Conclusions

In conclusion, in HD patients, several confounding factors, including reduced renal clearance, fluid overload, and chronic inflammation, limit the usefulness of NT-proBNP as a biomarker of cardiovascular disease. Our study demonstrated that NT-proBNP is unaffected by interdialytic weight gain, a readily available, though somewhat imprecise, indicator of fluid overload. Also, NT-proBNP is not a reliable marker of HFpEF, and has limited ability to identify LVSD (AUC 0.627). However, NT-proBNP adequately identifies patients with a history of AF (AUC 0.801), suggesting a potential role in detecting HD patients at increased risk of developing AF.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/kidneydial6020042/s1, Table S1: Raw data.

Author Contributions

Conceptualization, T.E.; methodology, T.E., M.D. and K.K.; software, T.E., M.D., K.K., A.B. and M.T.; validation, T.E., M.D., K.K. and P.M.; formal analysis, T.E., M.D., K.K. and M.T.; investigation, T.E., M.D., E.L. and A.B.; resources, T.E., M.D., P.M. and I.S.; data curation, T.E., M.D., K.K., P.M. and M.T.; writing—original draft preparation, T.E.; writing—review and editing, T.E., M.D., C.P., E.L., I.S. and A.B.; visualization, T.E., C.P., A.B. and M.T.; supervision, T.E.; project administration, T.E., M.D., P.M., K.K. and I.S.; funding acquisition, I.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted following the Declaration of Helsinki and approved by the Ethics Committee of the University of Thessaly, Faculty of Medicine (number of approval: 558/10-2-2017, approval date: 10 February 2017).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

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Kidneydial 06 00042 g001
Figure 1. Comparison of serum NT-proBNP levels between healthy individuals and HD patients. Serum NT-proBNP levels were significantly higher in HD patients than in healthy subjects. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.001.
Figure 1. Comparison of serum NT-proBNP levels between healthy individuals and HD patients. Serum NT-proBNP levels were significantly higher in HD patients than in healthy subjects. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.001.
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Kidneydial 06 00042 g002
Figure 2. Serum NT-proBNP in HD patients with residual diuresis of more or less than 500 mL/day. Serum NT-proBNP levels did not differ significantly between HD patients with residual diuresis of more or less than 500 mL/day (p > 0.05). Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the distribution of data density (A). ROC curve analysis revealed an AUC of 0.490 (p > 0.05) (B).
Figure 2. Serum NT-proBNP in HD patients with residual diuresis of more or less than 500 mL/day. Serum NT-proBNP levels did not differ significantly between HD patients with residual diuresis of more or less than 500 mL/day (p > 0.05). Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the distribution of data density (A). ROC curve analysis revealed an AUC of 0.490 (p > 0.05) (B).
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Figure 3. Serum NT-proBNP levels in HD patients with or without LVSD. NT-proBNP levels were significantly higher in HD patients with LVSD compared to those without LVSD. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.05 (A). ROC curve analysis yielded an AUC of 0.627 (p < 0.05) (B).
Figure 3. Serum NT-proBNP levels in HD patients with or without LVSD. NT-proBNP levels were significantly higher in HD patients with LVSD compared to those without LVSD. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.05 (A). ROC curve analysis yielded an AUC of 0.627 (p < 0.05) (B).
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Figure 4. Serum NT-proBNP levels in HD patients with or without a history of atrial fibrillation. Serum levels of NT-proBNP were markedly elevated in HD patients with atrial fibrillation. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.001 (A). ROC curve analysis revealed an AUC of 0.801 (p < 0.001) (B).
Figure 4. Serum NT-proBNP levels in HD patients with or without a history of atrial fibrillation. Serum levels of NT-proBNP were markedly elevated in HD patients with atrial fibrillation. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.001 (A). ROC curve analysis revealed an AUC of 0.801 (p < 0.001) (B).
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Figure 5. Serum NT-proBNP levels in HD patients with or without inflammation. Defining inflammation as a serum CRP level above 1 mg/dL, HD patients with inflammation had higher NT-proBNP levels than those without inflammation. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.05 (A). ROC curve analysis showed an AUC of 0.634 (p < 0.05) (B).
Figure 5. Serum NT-proBNP levels in HD patients with or without inflammation. Defining inflammation as a serum CRP level above 1 mg/dL, HD patients with inflammation had higher NT-proBNP levels than those without inflammation. Dots represent individual observations. Boxes show the interquartile range (IQR), with the horizontal line marking the median. Whiskers extend to 1.5 × IQR. Violin plots show the data’s density distribution. * p < 0.05 (A). ROC curve analysis showed an AUC of 0.634 (p < 0.05) (B).
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Table 1. Patients’ Characteristics.
Table 1. Patients’ Characteristics.
NMeanSD
Age (years)12366.0012.22
Males/Females87/36
Diabetes Mellitus (yes/no)46/77
Hypertension (yes/no)109/14
Coronary heart disease (yes/no)44/79
LVSD/HFpEF/No HF30/37/56
Atrial fibrillation (yes/no)34/89
Central venous catheter (yes/no)52/71
Duration on HD (months)12358.7650.50
White blood cells (c/μL)1237259.152551.88
Neutrophils (c/μL)1234929.511972.19
Lymphocytes (c/μL)1231693.52609.59
Hemoglobin (g/dL)12311.750.80
Platelet (c/μL)123210.9762.49
Creatinine (mg/dL)1236.322.18
Urea (mg/dL)123127.0226.51
Urea reduction ratio (%)12367.167.58
Interdialytic weight gain (kg)1233.201.05
Interdialytic weight gain (%)1234.181.29
Residual diuresis (mL)123291.06393.60
Res. diuresis > 500 mL/d (yes/no)47/76
Body mass index (kg/m2)12327.285.68
Albumin (g/dL)1233.620.31
Cholesterol (mg/dL)123134.1744.00
Triglyceride (mg/dL)123135.0776.96
Ferritin (ng/mL)123171.42174.65
Transferrin saturation (%)12319.0212.03
Calcium (mg/dL)1239.170.478
Phosphorous (mg/dL)1235.321.01
Intact parathyroid hormone (pg/mL)123342.69280.68
SGOT (U/L)12314.4711.81
SGPT (U/L)12312.159.20
Alkaline phosphatase (U/L)123202.3796.95
C-reactive protein (mg/dL)1231.260.85
C-reactive protein > 1 mg/dL (yes/no)67/56
Calprotectin (ng/mL)1232388.451373.96
NT-proBNP (pg/mL)1232218.451536.56
Table 2. Associations of serum NT-proBNP levels with patients’ characteristics.
Table 2. Associations of serum NT-proBNP levels with patients’ characteristics.
NNT-proBNP Medians (pg/mL)-Median (IQR)Rhop
Age123 0.0880.331
Male/Female87/361582.5 (1245.3–1903.85)/2006.8 (633.08–2920.4) 0.067
Diabetes Mellitus (yes/no)46/771697.5 (1340.9–2763.7)/1909.0 (1203.0–2734.5) 0.271
Hypertension (yes/no)109/141736.0 (1222.7–2763.7)/1868.8 (1544.1–2747.95) 0.661
Coronary Heart Disease (yes/no)44/792102.9 (1308.35–2918.6)/1696.0 (1241.8–2572.8) 0.160
HFpEF/no HF 37/561698.2 (1367.9–2741.6/1679.6 (1206.7–2714.5) 0.564
LVSD (yes/no)30/932244.8(1732.2–2866.6)/1688.8 (1222.7–2725.9) 0.037
Atrial fibrillation (yes/no)34/892763.7 (2105.6–4172.75)/1674.6 (1125.7–2102.9) <0.001
Central venous catheter (yes/no)52/711819.5 (1413.6–2747.95)/1698.2 (1201.2–2755.8) 0.338
Duration on HD123 0.0800.381
White blood cells123 0.2600.004
Neutrophils123 0.359<0.001
Lymphocytes123 0.0880.331
Hemoglobin123 −0.0950.295
Creatinine123 0.0170.856
Urea123 −0.0270.769
Urea reduction ratio123 −0.0760.403
Interdialytic weight gain (mL)123 −0.0170.855
Interdialytic weight gain (%)123 0.0050.954
Residual diuresis123 −0.0140.879
Res. dieresis > 500 mL (yes/no)47/761720.0 (1411.4–3086.6)/1946.6 (1256.5–2726.65) 0.860
Body mass index123 0.0160.859
Albumin123 −0.0290.753
Cholesterol123 −0.2230.013
Triglycerides123 −0.324<0.001
Ferritin123 0.0920.310
TSAT123 −0.1610.076
Calcium123 0.0340.711
Phosphorous123 −0.1320.145
Parathyroid hormone123 0.0240.796
Alkaline phosphatase124 0.0560.536
C-reactive protein (CRP)123 0.297<0.001
CRP > 1 mg/dL (yes/no)67/562006.8 (1373.4–3433.6)/1679.6 (1035.9–2411.35) 0.011
Calprotectin (ng/mL)123 0.2340.009
Calprotectin > median (yes/no)61/611894.8 (1552.9–2879.6)/1684.6 (1125.7–2667.5) 0.055
Comparison between groups: Mann–Whitney U test; Correlations between variables: Spearman’s correlation test.
Table 3. Independent determinants of serum NT-proBNP levels.
Table 3. Independent determinants of serum NT-proBNP levels.
B (Unstand.)S.E.β (Stand.)tpVIF
Constant1489557.1 2.6720.009
LVSD923.3286.2 3.2270.0021.196
Atrial fibrillation865.4315.4 2.7440.0081.289
Cholesterol−2.5653.375−0.073−0.7600.4501.250
Triglycerides−4.7331.677−0.271−2.8230.0061.235
Neutrophils0.3460.0890.4983.899<0.0012.189
CRP346.5163.20.2162.1230.0371.389
Calprotectin−0.4320.122−0.421−3.537<0.0011.903
Model summary: R = 0.653, R2 = 0.426, Adjusted R2 = 0.374, p < 0.001.
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MDPI and ACS Style

Divani, M.; Katsanaki, K.; Tziastoudi, M.; Makri, P.; Poulianiti, C.; Lykotsetas, E.; Balatsouka, A.; Stefanidis, I.; Eleftheriadis, T. NT-proBNP Levels in Hemodialysis Patients: Unrelated to Interdialytic Weight Gain, Limited in Detecting Left Ventricular Systolic Dysfunction, but May Identify Atrial Fibrillation. Kidney Dial. 2026, 6, 42. https://doi.org/10.3390/kidneydial6020042

AMA Style

Divani M, Katsanaki K, Tziastoudi M, Makri P, Poulianiti C, Lykotsetas E, Balatsouka A, Stefanidis I, Eleftheriadis T. NT-proBNP Levels in Hemodialysis Patients: Unrelated to Interdialytic Weight Gain, Limited in Detecting Left Ventricular Systolic Dysfunction, but May Identify Atrial Fibrillation. Kidney and Dialysis. 2026; 6(2):42. https://doi.org/10.3390/kidneydial6020042

Chicago/Turabian Style

Divani, Maria, Katerina Katsanaki, Maria Tziastoudi, Panagiota Makri, Christina Poulianiti, Evangelos Lykotsetas, Andriani Balatsouka, Ioannis Stefanidis, and Theodoros Eleftheriadis. 2026. "NT-proBNP Levels in Hemodialysis Patients: Unrelated to Interdialytic Weight Gain, Limited in Detecting Left Ventricular Systolic Dysfunction, but May Identify Atrial Fibrillation" Kidney and Dialysis 6, no. 2: 42. https://doi.org/10.3390/kidneydial6020042

APA Style

Divani, M., Katsanaki, K., Tziastoudi, M., Makri, P., Poulianiti, C., Lykotsetas, E., Balatsouka, A., Stefanidis, I., & Eleftheriadis, T. (2026). NT-proBNP Levels in Hemodialysis Patients: Unrelated to Interdialytic Weight Gain, Limited in Detecting Left Ventricular Systolic Dysfunction, but May Identify Atrial Fibrillation. Kidney and Dialysis, 6(2), 42. https://doi.org/10.3390/kidneydial6020042

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