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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2006  |  Volume : 17  |  Issue : 2  |  Page : 171-176
Influence of Erythropoietin Dose and Albumin Level on the Plasma Brain Natriuretic Peptide in Hemodialysis Patients


Department of Nephrology, King Saud University, Riyadh, Saudi Arabia

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   Abstract 

Brain natriuretic peptide (BNP) levels increase in patients with congestive heart failure. Theoretically, BNP levels can be helpful in the determination of the "dry weight" of hemodialysis patients. To evaluate the effect of hemodialysis on the plasma concentration of BNP and to determine the factors that affect BNP levels during hemodialysis in patients with chronic renal failure, we studied five stable patients with chronic renal failure. A total of 15 blood samples were obtained for BNP levels at 24, 48 and 72 hours after the last hemodialysis session. The plasma BNP levels did not change significantly either with ultrafiltration volume or with time since last dialysis. However, the BNP levels correlated positively with the erythropoietin (EPO) dose (r=0.98, P<0.001) and negatively with the serum albumin levels (r = 0.94, P=0.02). Univariate analysis showed that the EPO dose (P=0.001) and the albumin level (P=0.02) were significant predictors of BNP level. Adjusted multivariate analysis showed significant interaction between the EPO dose and the albumin level (P=0.01, P=0.03 respectively. In conclusion: the plasma BNP levels were not significantly influenced by ultrafiltration volume or time since last dialysis. However, the BNP levels may be a useful prognostic parameter for assessing the risk of cardiovascular morbidity and mortality in hemodialysis patients.

Keywords: Brain natriuretic peptide, Albumin, Erythropoietin.

How to cite this article:
Alsuwaida A. Influence of Erythropoietin Dose and Albumin Level on the Plasma Brain Natriuretic Peptide in Hemodialysis Patients. Saudi J Kidney Dis Transpl 2006;17:171-6

How to cite this URL:
Alsuwaida A. Influence of Erythropoietin Dose and Albumin Level on the Plasma Brain Natriuretic Peptide in Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2020 Jul 6];17:171-6. Available from: http://www.sjkdt.org/text.asp?2006/17/2/171/35786

   Introduction Top


Brain natriuretic peptide (BNP) is a hormone released from myocardial cells in response to volume expansion and possibly to increased wall stress. The half-life of plasma BNP in normal subjects is approximately 20 minutes, which makes it a useful tool for assessing current left ventricular hemodynamic status.[1] The pathophysiologic and clinical relevance of BNP assays in the classification and predication of mortality in patients with heart failure has been shown in several studies. [2],[3],[4]

Patients in renal failure have markedly elevated BNP levels, which typically decline after dialysis sessions.[5],[6] It is unclear whether the elevations in BNP levels are due to volume overload (leading to increased BNP secretion), decreased metabolism and clearance of BNP, or decreased cardiac function.

Establishing volume status in patients on hemodialysis (HD) is extremely important. However, symptoms and physical findings may not be sufficiently sensitive to make an accurate estimation. Sequential BNP measure­ments may have potential application in monitoring the volume status of HD patients. Serial BNP levels may also be used to monitor and manage the ultrafiltration volume required in order to reach the optimal 'dry weight' for HD patients.

We hypothesized that plasma BNP levels will correlate positively with the ultrafiltration volume and time since last dialysis in HD patients. We also examined the influence of other factors particular to dialysis patients. These include: dialysis dose, parathyroid level, serum albumin level, and erythropoietin (EPO) dose.


   Patients and Methods Top


We measured plasma BNP levels 24, 48 and 72 h since last HD in 5 patients who have been undergoing 4 hours of three times weekly chronic HD for at least 6 months. The ethics committee of Security Force Hospital approved the protocol and informed consent was obtained from all participants.

All patients were clinically stable with no clinical evidence of active infection or congestive heart failure; all patients had a normal ejection fraction ( > 50%) in the two dimensional echocardiogram).

Blood for BNP measurement was drawn into a chilled glass tube containing disodium EDTA and aprotinin, and centrifuged imme­diately. The plasma was frozen and stored at -80°C until assayed for BNP using a well­established immunoradiometric assay (IRMA).


   Statistical Analysis Top


The statistical analyses were conducted using SAS software. Results are expressed as mean ± standard deviation. A Pearson's linear correlation coefficient (or a Spearman's test if any variable was ordinal and/or not normally distributed) was used for correlation between variables. To establish which variables were independently associated to BNP serum levels, a stepwise multiple linear regression analysis was performed, with a forward selection strategy, using an F value of p <0.05 as the selection criterion. A mixed model for repeated measurements was used to assess the simultaneous effect of time since last dialysis and ultrafiltration volume on plasma BNP level. P value < 0.05 was set for statistical significance.


   Results Top


Demographic characteristics of patients are shown in [Table - 1]. All enrolled patients completed the study according to the protocol. The mean age of the patients was 31.8 years. All the patients were on EPO for their anemia.

[Figure - 1] shows the plasma BNP levels in patients at 24, 48 and 72h since the last HD. There was no significant variation in the plasma BNP levels at the indicated times (F=0.02, P=0.98). The ultrafiltration volume strongly correlated with the time since last HD (r=0.75, P=0.001). However, there was no significant relationship between BNP plasma level and ultrafiltration volume (F<0.05, P=0.83).

[Figure - 2] shows that the mean BNP concen­tration strongly correlated with the EPO dose, (r=0.98, P<0.001) but not with the hemoglobin concentration (r= -0.4, P=0.46).

[Figure - 3],[Figure - 4] show that the serum albumin level correlated negatively with the EPO dose (r= -0.95, P=0.01) and BNP level (r=­0.94, P=0.02), respectively.

Univariate analysis of the EPO dose (F=132, P=0.001) and the albumin level (F=23.5, P=0.02) showed that they were significant predictors of BNP level.

The multivariate analysis showed a signi­ficant interaction between the albumin level and the EPO dose (F=1110, P=0.02). Even after adjusting for this interaction, the EPO dose (F=2483, P=0.01) and the albumin level (F=586, P=0.03) continued to be significant predictors of the BNP level. In order to further scrutinize this interaction, we classified the albumin level into 'Normal' if it was equal or greater than 40 or 'Low' if it was not. The patients with low albumin had higher BNP levels and required higher doses of EPO. [Table - 2] shows the mean of EPO and BNP level based on their albumin level.

There was no correlation between the mean BNP level and the calcium-phosphorus product (r=0.5, P=0.35) or the parathyroid level (r=0.05, P=0.9), which suggested that the BNP level was not affected by bone­related factors.


   Discussion Top


The BNP levels decrease after HD, similar to the other middle molecules between 300 to 1200 Daltons. Our study showed that the BNP levels returned to baseline values within 24h post standard dialysis with no significant changes during the following 48 or 72h. The immediately post dialysis level of BNP was lower than the baseline level of BNP because of the relatively slow equilibration with the extravascular space similar to other middle molecules.

Several clinical trials indicated that BNP levels were clinically useful for the diagnosis of patients with suspected heart failure. [2],[3],[4],[7],[8],[9] However, the clinical relevance of the BNP assay as a diagnostic marker of cardiac function in patients with end-stage renal disease is doubtful. [10],[11] The patients on HD show signi­ficant variations in their intravascular volume during the interdialysis period suggesting that BNP levels could be sensitive to these variations. However, the results of this study showed no significant relationship between the ultrafiltration volume and the BNP levels in HD patients. Furthermore, the range of the BNP levels in stable dialysis patients is very wide, which makes choosing a cutoff point to discriminate those with congestive heart failure not feasible.

The BNP measurements seem to show better clinical performance as a prognostic rather than a diagnostic marker. Recently, several well-designed studies demonstrated the prognostic relevance of the BNP assays in patients with both heart failure [12],[13] and acute coronary syndrome. [14],[15],[16] Cataliotti et al [17] and Go to et al [18] reported that high levels of BNP were significantly associated with a greater risk of cardiovascular events in dialysis patients without clinical evidence of congestive heart failure.

Kumagai et al [19] examined the relationship between EPO and chronic heart failure in patients on maintenance HD and reported a significant correlation between BNP levels and the EPO dose in patients with heart failure. However, our study showed that the correlation between EPO and BNP was very strong and existed even in the absence of heart failure, and is not related to anemia. We postulate two possible explanations for this observation; the EPO may stimulate synthesis of BNP in the heart, or the BNP may behave as an acute phase reactant in patients with systemic inflammation usually requiring a higher dose to maintain adequate hemoglobin levels. The latter explanation can further explain the higher BNP level in patients with low albumin level. These observations substantiate the use of BNP levels as a prognostic marker for patients on hemodialysis.

In summary, plasma BNP levels were not significantly influenced by ultrafiltration volume. However, BNP levels may be a useful prognostic parameter for assessing the risk of cardiovascular morbidity and mortality in hemodialysis patients.

 
   References Top

1.Holmes SJ, Espiner EA, Richards AM, Yandle TG, Frampton C. Renal, endocrine, and hemodynamic effects of human brain natriuretic peptide in normal man. J Clin Endocrinol Metab 1993;76:91-6.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Nakamura M, Endo H, Nasu M, Arakawa N, Segawa T, Hiramori K. Value of plasma B type natriuretic peptide measurement for heart disease screening in a Japanese population. Heart 2002;87:131-5.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Koglin J, Pehlivanli S, Schwaiblmair M, et al. Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure. J Am Coll Cardiol 2001; 38:1934-41.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Ishii J, Nomura M, Okuma T, et al. Risk stratification using serum concentrations of cardiac troponin T in patients with end­stage renal disease on chronic maintenance dialysis. Clin Chim Acta 2001;312:69-79.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Mair J, Friedl W, Thomas S, Puschendorf B. Natriuretic peptides in assessment of left-ventricular dysfunction. Scand J Clin Lab Invest Suppl 1999;230:132-42.  Back to cited text no. 5  [PUBMED]  
6.Jensen KT, Carstens J, Ivarsen P, Pedersen EB. A new, fast and reliable radioimmunoassay of brain natriuretic peptide in human plasma. Reference values in healthy subjects and in patients with different diseases. Scand J Clin Lab Invest 1997;57:529-40.  Back to cited text no. 6    
7.Cowie MR, Mendez GF. BNP and congestive heart failure. Prog Cardiovasc Dis 2002;44:293-321.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.McGeoch G, Lainchbury J, Town G, et al. Plasma brain natriuretic peptide after long­term treatment for heart failure in general practice. Eur J Heart Fail 2002;4:479-83.  Back to cited text no. 8    
9.McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 2002;106:416-22.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Ishii J, Nomura M, Okuma T, et al. Risk stratification using serum concentrations of cardiac troponin T in patients with end­stage renal disease on chronic maintenance dialysis. Clin Chim Acta 2001;312:69-79.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Osajima A, Okazaki M, Tamura M, et al. Comparison of plasma levels of mature adrenomedullin and natriuretic peptide as markers of cardiac function in hemodialysis patients with coronary artery disease. Nephron 2002;92:832-9.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Sayama H, Nakamura Y, Saito N, Kinoshita M, Suda M. Relationship between left ventricular geometry and brain natriuretic peptide levels in elderly subjects. Gerontology 2000;46:71-7.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Selvais PL, Donckier JE, Robert A, et al. Cardiac natriuretic peptides for diagnosis and risk stratification in heart failure: influences of left ventricular dysfunction and coronary artery disease on cardiac hormonal activation. Eur J Clin Invest 1998;28:636-42.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Omland T, Aakvaag A, Bonarjee V, et al. Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myo­cardial infarction. Comparison with plasma atrial natriuretic peptide and n-terminal proatrial natriuretic peptide. Circulation 1996;93:1963-1969.  Back to cited text no. 14    
15.Horio T, Shimada K, Kohno M, et al. Serial changes in atrial and brain natriuretic peptides in patients with acute myocardial infarction treated with early coronary angioplasty. Am Heart J 1993;126:292-9.  Back to cited text no. 15    
16.Arakawa N, Nakamura M, Aoki H, Hiramori K. Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction. J Am Coll Cardiol 1996; 27:1656-61.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Cataliotti A, Malatino LS, Jougasaki M, et al. Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling. Mayo Clin Proc 2001;76:1111-9.  Back to cited text no. 17  [PUBMED]  
18.Goto T, Takase H, Toriyama T, et al. Increased circulating levels of natriuretic peptides predict future cardiac event in patients with chronic hemodialysis. Nephron 2002;92:610-5.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Kumagai J, Yorioka N, Kawanishi H, et al. Relationship between erythropoietin and chronic heart failure in patients on chronic hemodialysis. J Am Soc Nephrol 1999; 10:2407-11.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Abdulkareem Alsuwaida
Department of Nephrology, King Saud University, P.O. Box 2925, Riyadh 11461
Saudi Arabia
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PMID: 16903623

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    Abstract
    Introduction
    Patients and Methods
    Statistical Analysis
    Results
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