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Association Between N-Terminal Propeptide B-Type Natriuretic Peptide and Markers of Hypervolemia

Gangji AS|Al Helal B|Churchill DN|Brimble KS|Margetts PJ
Peritoneal Dialysis International, Vol. 28, pp. 308–311
OBJECTIVE: Patients with end-stage renal disease have a higher risk of developing premature cardiovascular disease (1). Volume expansion in peritoneal dialysis (PD) patients is associated with cardiovascular disease (2); however, accurate volume assessment is difficult. B-type natriuretic peptide (BNP), N-terminal propeptide BNP (N-BNP), and bioelectrical impedance analysis (BIA) have been proposed as adjunctive measures to aid in diagnosing hypervolemia. B-type natriuretic peptide is a 32 amino acide peptide of cardiac origin that is released in response to ventricular wall stretch. The pro-hormone is cleaved to form an active and an inactive BNP molecule. The inactive N-BNP has a longer half-life. In dialysis patients, N-BNP is associated with cardiovascular and overall mortality; however, its role in predicting volume status in PD patients has not been extensively studied (3). Bioelectrical impedance analysis has been used in PD patients to determine volume status and correlates highly with gold standard isotope dilution methods (4). The impedance ratio determined at 5 kHz:200 kHz (5), the resistance-reactance (RXc) graph method proposed by Piccoli et al. (6), and the ratio of extracellular water to total body water (ECW:TBW) have all been shown to correlate with clinical evidence of hypervolemia. Other markers of hypervolemia in PD patients include high peritoneal transport status (7) and hypoalbuminemia (8). The aim of the present study was to determine if N-BNP correlates with markers of hypervolemia, as measured by BIA, serum albumin, and peritoneal transport status. A second objective was to test for correlations between N-BNP and troponin T (TnT), a marker of cardiovascular disease, and between NBNP and phase angle, a surrogate marker predicting mortality in PD patients.
CONCLUSION: Several methods that have correlated previously with clinical evidence of hypervolemia were used in assessing volume status. This was done to avoid spurious findings and in recognition of the limits of each technique in volume assessment. N-BNP correlated with all five predictors of hypervolemia. Unlike the ECW:TBW ratio, the impedance ratio and the RXc graph method have no underlying assumptions regarding body geometry and hydration status. In addition, these methods use raw data rather than volumes calculated based on assumptions, and these two techniques have been proposed to be better predictors of volume status (12). Hypoalbuminemia has been associated with inflammation and malnutrition and is a marker of overhydration in PD patients (8). In the present study, hypoalbuminemia was a valid marker of fluid overload, as low serum albumin was associated with N-BNP but did not correlate with CRP or SGA. In addition, none of the hypervolemic markers correlated with SGA; however, serum albumin was associated with all other markers of hypervolemia. N-terminal BNP is eliminated by the renal route and it has been postulated that N-BNP levels are elevated due to reduced clearance (13). In the present study, N-BNP was not associated with reduced renal clearance or residual urine output, thus making it less likely that these two variables were confounders; this is consistent with the reports by Alehagen et al (14). Elevated TnT levels have also been shown to be predictive of increased mortality in hemodialysis patients (15). The finding of N-BNP’s association with TnT and phase angle, a marker of death in PD patients (16), may imply that N-BNP is also a predictor of poor prognosis. In prospective studies involving PD and hemodialysis patients respectively, Wang et al. and Zoccali et al. found an association between N-BNP and mortality (3, 17). The present study has several limitations. The design is crosssectional with a small sample size. The results establish correlations but a long-term prospective study is required to determine if N-BNP is a valid surrogate marker for hypervolemia and if it can be used to manage volume in PD patients. In conclusion, this study demonstrates that N-BNP correlates with different markers of volume overload and surrogate markers predicting death in PD patients. A prospective study with volume adjustment based on N-BNP would be required to assess if this potential marker of hydration status can maintain PD patients in a euvolemic state.
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