NDT Advance Access originally published online on April 23, 2007
Nephrology Dialysis Transplantation 2007 22(7):2093-2094; doi:10.1093/ndt/gfm234
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Removal of BNP and inflammatory cytokines by haemodiafiltration in refractory heart failure
Email: amir.kazory{at}medicine.ufl.eduSir,
We read with great interest the paper by Libetta et al., recently published in your journal [1]. It evaluates the role of intermittent haemodiafiltration (iHDF) in refractory congestive heart failure (CHF), and tries to explore the pathophysiological mechanisms for restoration of diuretic responsiveness. However, in our opinion, a close look at the methodology of the study gives rise to a few concerns that could adversely affect the results and conclusions.
First, brain natriuretic peptide (BNP) is degraded and eliminated from plasma primarily by neutral endopeptidase; glomerular filtration has only a minor role in its removal [2]. In this study, both diuretic therapy and iHDF significantly lowered circulating levels of BNP. The authors hypothesize that rapid and significant decrease of BNP in iHDF patients is due to rapid plasma volume reduction. While this can be true in the diuretic group, it should be interpreted cautiously in the iHDF group, due to the role of filtration in removal of BNP. In fact, a number of studies exploring the use of BNP in assessing the extracellular fluid volume in dialysis patients have failed to find any correlation between BNP levels and pre- and post-dialysis hydration status [3,4]. Therefore, it is more likely that BNP reduction in the iHDF group is mainly related to its removal by filtration rather than a reflection of a change in plasma volume. Besides, after termination of iHDF therapy, levels of BNP immediately started to rise, while the levels continued to decrease in the diuretic group during the 30-day follow-up period (Figure 1 of that paper). This implies that volume status might actually have been better preserved over time in the diuretic group, and that the decrease in BNP levels were mainly due to removal by iHDF.
Second, the authors observed a significant reduction of pro-inflammatory cytokines in the iHDF group and concluded that lowering of these cytokines is associated with a strong reduction of BNP in these patients (used as an indicator of improvement of cardiac function). However, since the inflammatory state per se is not modified by using iHDF, it is not clear why authors have hypothesized that removal of these cytokines (simultaneously with elimination of anti-inflammatory cytokines) would have a positive impact on cardiac function. Indeed, the authors failed to show any simultaneous increase in the levels of anti-inflammatory cytokines, which remained below detectable limits during the whole period of the study. Besides, the fact that the authors did not find any correlation between serum levels of BNP and pro-inflammatory cytokines in iHDF group can reflect the differences in kinetics and removal rate of these substances with iHDF rather than a change in the inflammatory state and/or volume status.
In summary, we agree with the authors that iHDF demonstrates short-term efficiency in rapid removal of fluid and solutes (including BNP and inflammatory cytokines) in patients with diuretic-resistant CHF. However, the pathophysiological mechanisms for restoration of diuretic responsiveness and potential impact of iHDF on CHF-associated chronic inflammatory state need further studies specifically designed to address these issues.
Conflict of interest statement. None declared.
Division of Nephrology
Hypertension, and Transplantation
University of Florida, Gainesville
Florida, USA
References
- Libetta C, Sepe V, Zucchi M, et al. Intermittent haemodiafiltration in refractory congestive heart failure: BNP and balance of inflammatory cytokines. Nephrol Dial Transplant (2007) [Epub ahead of print].
[Abstract/Free Full Text] - Mark PB, Petrie CJ, Jardine AG. Diagnostic, prognostic, and therapeutic implications of brain natriuretic peptide in dialysis and nondialysis-dependent chronic renal failure. Semin Dial (2007) 20:40–49.[CrossRef][Web of Science][Medline]
- Fagugli RM, Palumbo B, Ricciardi D, et al. Association between brain natriuretic peptide and extracellular water in hemodialysis patients. Nephron Clin Pract (2003) 95:c60–c66.[CrossRef][Web of Science][Medline]
- Lee SW, Song JH, Kim GA, et al. Plasma brain natriuretic peptide concentration on assessment of hydration status in hemodialysis patient. Am J Kidney Dis (2003) 41:1257–1266.[CrossRef][Web of Science][Medline]
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