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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2018  |  Volume : 29  |  Issue : 4  |  Page : 872-878
The impact of blood flow rate on dialysis dose and phosphate removal in hemodialysis patients


1 Department of Nephrology, Dialysis and Renal Transplantation, Faculty of Medicine, Mohammed V Military Hospital, Mohammed V, Souissi University, Rabat; Department of Nephrology and Dialysis, 5th Military Hospital, Guelmim, Morocco
2 Department of Nephrology and Dialysis, 5th Military Hospital, Guelmim; Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fes, Morocco
3 Department of Nephrology, Dialysis and Renal Transplantation, Faculty of Medicine, Mohammed V Military Hospital, Mohammed V, Souissi University, Rabat, Morocco

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Date of Submission30-Jul-2017
Date of Decision24-Sep-2017
Date of Acceptance28-Sep-2017
Date of Web Publication28-Aug-2018
 

   Abstract 

The inadequacy of dialysis and hyperphosphatemia are both associated with morbidity and mortality in chronic hemodialysis (HD) patients. Blood flow rate (BFR) during HD is one of the important determinants of increasing dialysis dose. The aim of this study was to determine the effect of increasing BFR on dialysis dose and phosphate removal. Forty-four patients were included in a cross-sectional study. Each patient received six consecutive dialysis sessions as follows: three consecutive sessions with a BFR of 250 mL/min, followed by three others with BFR of 350 mL/min without changing the other dialysis parameters. Patients' body weight was recorded, and blood samples (serum urea and phosphate) were collected before and after each dialysis session. For assessing the efficacy of dialysis, urea reduction ratio (URR), Kt/VDiascan (Kt by Diascan and V by Watson), Kt/V Daugirdas (Daugirdas 2nd generation), equilibrated Kt/V, and phosphate reduction rate (PRR) were used. The increase of BFR by 100 mL/min resulted in a significant increase of URR, Kt/V Diascan, Kt/VDaugirdas, equilibrated Kt/V, and PRR: URR; 75.41 ± 5.60; 83.51 ± 6.12; P <0.001), (Kt/VDiascan; 1.28 ± 0.25; 1.55 ± 0.15; P <0.001), (Kt/VDaugirdas; 1.55 ± 0.26; 2.10 ± 0.61; P = 0.001), equilibrated Kt/V; 1.40 ± 0.19; 1.91 ± 0.52; P = 0.001), and (PRR; 50.32 ± 12.22; 63.66 ± 13.10; P = 0.010). Adequate dialysis, defined by single-pool Kt/V ≥1.4, was achieved using two different BFRs: 250 and 350 mL/min, respectively, in 73% and 100% of the cases. Increasing the BFR by 40% is effective in increasing dialysis dose and phosphate reduction rate during high-flux HD. The future prospective studies are needed to evaluate the impact of increasing BFR on phosphate removal using the total amount of phosphate removed, and also evaluate the cardiovascular outcome of phosphate reduction and dialysis improvement.

How to cite this article:
Rafik H, Aatif T, El Kabbaj D. The impact of blood flow rate on dialysis dose and phosphate removal in hemodialysis patients. Saudi J Kidney Dis Transpl 2018;29:872-8

How to cite this URL:
Rafik H, Aatif T, El Kabbaj D. The impact of blood flow rate on dialysis dose and phosphate removal in hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Jul 16];29:872-8. Available from: http://www.sjkdt.org/text.asp?2018/29/4/872/239654

   Introduction Top


In managing regular hemodialysis (HD) patients, we need to ensure the optimal dialysis prescription for each patient and quantify the amount of dialysis actually delivered to the patient.[1] Adequate delivery of dialysis dose has a significant effect in decreasing morbidity and mortality of chronic HD patients.[2] The most common marker to quantify dialysis adequacy is Kt/V index where K is the effective clearance of urea (commonly accepted as the marker solute for uremic toxicity), t is the duration of the session, and V is the volume of urea distribution. The Kt/V is the exponent of the nonlinear curve describing the decrease of urea concentration during one dialysis session.[3] The European Best Practice Guidelines recommend that the dialysis dose should be measured at least monthly; urea reduction ratio (URR) above 65%, single-pool Kt/Vurea of at least 1.4 and double-pool Kt/Vurea of at least 1.2 should be maintained.[4] To achieve an adequate Kt/V, many factors could be optimized as follows: dialyzer size and characteristics, dialysis time, dialysis frequency, dialysate flow rate, and blood flow rate (BFR). However, the use of some of these methods is not always possible due to clinical intolerance and economic constraints.[5]

Hyperphosphatemia is highly prevalent in HD patients and is a major risk factor for vascular calcifications.[6] In addition, increased serum phosphorus levels have been reported to be an independent prognostic factor for patients' survival.[7] Therefore, it is necessary to improve the removal of this molecule.[8] Phosphate clearance is affected by dialyzer membrane surface area and permeability, blood and dialysate flow rate, dialysis time and frequency, and HD modality.[9]

The aim of this study was to determine the effect of increasing BFR on dialysis dose evaluated by URR and Kt/V, and on phosphate removal assessed by phosphate reduction rate (PRR).


   Methods Top


The trial was designed as a cross-sectional, single-center study comparing the impact of increasing BFR from 250 to 350 mL/min on dialysis dose and phosphate removal. This study was conducted on HD patients in a single-dialysis center in the 5th Military Hospital of Guelmim, Morocco. The study protocol was approved by the Committee on Ethics and Research of the Institution. Forty-four dialysis patients were included in the study.

The inclusion criteria were as follows: duration on HD therapy of at least three months, three dialysis sessions per week for 4 hours each, absence of severe cardiovascular disease, good vascular access, adult age, and patient's consent.

Baseline demographic and clinical data, including age, sex, height, dry weight, body mass index (BMI), causes of end-stage renal disease (ESRD), and comorbidities, were collected at the study entry. The present study was divided into two phases, each phase comprised three HD sessions per patient. In the first phase, the BFR was regulated at 250 mL/min; and in the second phase, it was increased to 350 mL/min without changing the other dialysis parameters for each patient. The patients' body weight was recorded, and blood samples (serum urea and phosphate) were collected before and after each dialysis session. The initial sample was obtained from the arterial line of the extracorporeal system avoiding dilution with either heparin or washing solution. The final sample was obtained at the end of the dialysis session, the ultrafiltration rate was set to zero, and the blood pump rate was reduced to 100 mL/min. Fifteen seconds after reducing the blood flow, the sample was then drawn from the arterial line. For assessing the efficacy of dialysis, URR, Kt/VDiascan, Kt/VDaugirdas, equilibrated Kt/V (Kt/Vequi), and PRR were used.

URR is the percentage fall in blood urea achieved by a dialysis session (Appendix 1).[10]



A Gambro model AK 200 ULTRA S dialysis machine (Gambro-Hospal, Lund, Sweden) equipped with the DIASCAN system was used in each dialysis. Online urea clearance measurement deployed in the DIASCAN system, automatically determines the urea clearance K via a positive or negative conductivity bolus. With K and effective dialysis duration t given, effective cleared plasma Kt is easily calculated. For urea distribution volume V, Watson formula is applied (Appendix 2), resulting in Kt/VDiascan.[11]



Kt/VDaugirdas was calculated using Daugirdas second-generation formula (Appendix 3) which is the most accurate equation to estimate single-pool Kt/V (spKt/V).[12] Kt/Vequi was developed to account for the effects of urea rebound and more accurately reflect the delivered dose of dialysis. It was calculated from Kt/VDaugirdas using an equation (Appendix 4) that changes depending on whether the patient was dialyzed with arteriovenous access or strictly venous access.[13]





PRR is the percentage fall in blood phosphate achieved by a dialysis session (Appendix 5).



Data with continuous variables were presented as the mean ± standard deviation. Categorical variables were presented as effective and percentage. The paired student t-test was used to compare variables. A value of P <0.05 was considered statistically significant. Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS) version 10.0 for Windows (SPSS Inc., Chicago, IL, USA).


   Results Top


Patient characteristics

Our study included 44 chronic HD patients undergoing regular dialysis three times a week. Twenty-four patients were male and 20 were female, their mean age was 55.36 ± 15.82 years, and the median duration on dialysis was 61.81 months. Causes of ESRD were diabetes (45.45%), hypertension (13.63%), lithiasis (4.54%), gout (4.54%), reflux (4.54%), glomerulonephritis (4.54%), and unknown (22.72%). Twenty patients (45.45%) were diabetic, six (13.63%) had ischemic cardiomyopathy, and four (9.09%) had peripheral arterial occlusive disease. None of the patients had preserved residual renal function. The patients' BMI ranged from 17 to 31.40 kg/m2 (mean 23.07 ± 4.50 kg/m2). The detailed characteristics of the study patients are shown in [Table 1].
Table 1: Characteristics of patients included in the study.

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Treatment parameters

Each patient received six consecutive HD sessions with an effective dialysis time of 240 minutes, using high permeability polyamide dialyzers of 2.1 m2 in 50%, 1.7 m2 in 31.81 %, and 1.4 m2 in 18.18%, at an effective dialysate flow rate of 500 ml/min. A new dialyzer was used each time. The vascular access utilized was an arteriovenous fistula in 81.81%, tunneled catheter in 9.09%, and arteriovenous graft in 9.09%. Low-molecular-weight heparin was used to prevent thrombosis in the extra-corporeal circuit (Enoxaparine 4000 IU in 81.81% and Enoxaparine 2000 IU in 18.18%). There were no dialysis incidents such as hypertension or hypotension during the study. [Table 2] shows the dialysis parameters.
Table 2: Dialysis parameters in the study patients.

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Dialysis dose data

By increasing BFR from 250 to 350 mL/min, the parameters of dialysis adequacy, namely URR, Kt/VDiascan, Kt/VDaugirdas, and Kt/Vequi rose significantly (URR; 75.41 ± 5.60; 83.52 ± 6.12; P <0.001), (Kt/VDiascan; 1.28 ± 0.25; 1.55 ± 0.15; P <0.001), (Kt/VDaugirdas; 1.55 ± 0.26; 2.10 ± 0.61; P = 0.001), and (Kt/Vequi; 1.40 ± 0.19; 1.91 ± 0.52; P = 0.001) [Table 3].
Table 3: Effect of increasing blood flow rate on dialysis efficiency.

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Adequate dialysis, defined by spKt/V ≥1.4, was achieved according to two methods: Kt/V Diascan, Kt/VDaugirdas, respectively, in 19.90% and 73% of the cases using a BFR of 250 mL/min and in 70.70 and 100% of the cases using a BFR of 350 mL/min.

Phosphate removal data

There was no significant difference between the predialysis serum phosphate in the two BFR groups (42.95 ± 9.59; 43.95±10.35 mg/L; P = 0.437).

PRR improved from 50.32 ± 12.22 to 63.66 ± 13.10 (P = 0.010) when BFR was increased from 250 to 350 mL/min [Table 3].


   Discussion Top


The BFR is different in many countries and the optimal BFR has been unclear. The Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that in the United States, patients with BFR >400 mL/min account for 83.6% of the HD patients. In Canada and some European countries, patients with BFR ≥250 mL/min account for about 98% of the HD patients.[14] However, in Japan, patients with BFR ≥250 mL/min account for 18% and the BFR prescribed is usually 200 mL/min for a typical HD treatment.[15] Some investigators suggest that the use of low BFR may contribute to longer survival by facilitating the longer maintenance of arteriovenous fistula.[15],[16] On the contrary, other studies have demonstrated that the increased BFR is important for optimizing dialysis dose,[5] and inadequate dialysis dose is associated with increased mortality.[2] The results of HD study have indicated that, with a schedule of thrice-weekly dialysis, an increased dose of dialysis did not improve survival or reduce the rate of hospitalization as compared with a standard dose.[17] In this study, we demonstrated that Kt/VDaugirdas was ≥1.4 in 73% of cases with a BFR of 250 mL/min and in 100% of cases with a BFR of 350 mL/min. Several observational studies have examined the relationship between BFR and dialysis dose. Chang et al showed that BFR was positively correlated with spKt/V (ß = 0.108, P = 0.001) and odds ratio of patients with BFR <250 mL/min to have inadequate dialysis dose (spKt/V ≤1.2) was 1.5 (95% CI, 1.03 to 2.20; P = 0.036).[18] Borzou et al reported that 16.7% of patients had Kt/V higher than 1.3 using BFR of 200 mL/min whereas 26.2% of patients had Kt/V higher than 1.3 using BFR of 250 mL/min HD.[19] Kim et al reported that by increasing the BFR by 15%–20% in patients with low efficiency dialysis (Kt/V less than of 1.2), the efficiency of dialysis would increase by 4%.[20]

It is known that hyperphosphatemia is a major risk factor for vascular calcifications and is independently associated with increased risk of death in HD patients.[6],[7] Dietary restriction and phosphate binding agents are usually used to control serum phosphate levels but have limited efficacy.[21] Phosphate removal during HD is limited largely due to the intra-cellular location of most inorganic phosphorus and can be improved by hemodialfiltration, increased dialysis frequencies, and extended treatment times.[9] Serum phosphate levels decrease sharply during the first 60–120 min of dialysis and remain relatively constant thereafter, apparently independent of dialyzer blood flow and type of dialyzer membrane.[22],[23] Gutzwiller et al assessed the effectiveness of increasing BFR on clearance of potassium and phosphate with dialysis and showed that increasing the BFR was effective in increasing the clearance of potassium but was not effective in phosphorus clearance.[22] In contrast, increasing BFR in our study by 40% was associated significantly with an increase in PRR. Our result might be explained by the fact that we have chosen PRR which is certainly not a good marker of phosphate removal instead of the total amount of phosphate removed.


   Conclusion Top


Increasing BFR is effective in increasing dialysis dose and PRR during high-flux HD. The future prospective studies should evaluate the impact of increasing BFR on phosphate removal using the total amount of phosphate removed and also evaluate the cardiovascular outcome of phosphate reduction and dialysis improvement.

Conflict of Interest: None declared.

 
   References Top

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Locatelli F, Buoncristiani U, Canaud B, Köhler H, Petitclerc T, Zucchelli P, et al. Dialysis dose and frequency. Nephrol Dial Transplant 2005;20:285-96.  Back to cited text no. 1
    
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Port FK, Ashby VB, Dhingra RK, Roys EC, Wolfe RA. Dialysis dose and body mass index are strongly associated with survival in hemo-dialysis patients. J Am Soc Nephrol 2002;13: 1061-6.  Back to cited text no. 2
    
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Aatif T, Hassani K, Alayoud A, Zajjari Y, Maoujoud O, Benyahia M, et al. Quantification of hemodialysis dose: What kt/V to choose? Int J Artif Organs 2014;37:29-38.  Back to cited text no. 3
    
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European Best Practice Guidelines Expert Group on Hemodialysis, European Renal Association. Section II. Haemodialysis adequacy. Nephrol Dial Transplant 2002;17 Suppl 7:16-31.  Back to cited text no. 4
    
5.
Mandolfo S, Borlandelli S, Ravani P, Imbasciati How to improve dialysis adequacy in patients with vascular access problems. J Vasc Access 2006;7:53-9.  Back to cited text no. 5
    
6.
Block GA. Control of serum phosphorus: Implications for coronary artery calcification and calcific uremic arteriolopathy (calciphylaxis). Curr Opin Nephrol Hypertens 2001;10:741-7.   Back to cited text no. 6
    
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Palmer SC, Hayen A, Macaskill P, Pellegrini Craig JC, Elder GJ, et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: A systematic review and meta-analysis. JAMA 2011;305:1119-27.  Back to cited text no. 7
    
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Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009; 76(Suppl 113) :S1-130.  Back to cited text no. 8
    
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Kuhlmann MK. Phosphate elimination in modalities of hemodialysis and peritoneal dialysis. Blood Purif 2010;29:137-44.  Back to cited text no. 9
    
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Lowrie EG, Lew NL. The urea reduction ratio (URR): A simple method for evaluating hemodialysis treatment. Contemp Dial Nephrol 1991; 12:11-20.  Back to cited text no. 10
    
11.
Watson PE, Watson ID, Batt RD. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr 1980;33:27-39.  Back to cited text no. 11
    
12.
Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume kt/V : An analysis of error. J Am Soc Nephrol 1993;4:1205-13.  Back to cited text no. 12
    
13.
Kotanko P, Levin N, Gotch F. Dialysis delivery and adequacy. In: Molony D, Craig J, editors. Evidenced Based Nephrology. Oxford: Wiley Blackwell; 2008. p. 423-30.  Back to cited text no. 13
    
14.
Arbor Research Collaborative for Health. DOPPS Practice Monitor. Available from: http://www.dopps.org/DPM/Default.aspx. [Last accessed on 2016 Dec 19].  Back to cited text no. 14
    
15.
Kimata N, Karaboyas A, Bieber BA, Pisoni RL, Morgenstern H, Gillespie BW, et al. Gender, low kt/V, and mortality in Japanese hemodialysis patients: Opportunities for improvement through modifiable practices. Hemodial Int 2014;18:596-606.  Back to cited text no. 15
    
16.
Pisoni RL, Arrington CJ, Albert JM, Ethier J, Kimata N, Krishnan M, et al. Facility hemodialysis vascular access use and mortality in countries participating in DOPPS: An instrumental variable analysis. Am J Kidney Dis 2009;53:475-91.  Back to cited text no. 16
    
17.
Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, et al. Effect of dialysis dose and membrane flux in mainte-nance hemodialysis. N Engl J Med 2002;347: 2010-9.  Back to cited text no. 17
    
18.
Chang KY, Kim SH, Kim YO, Jin DC, Song HC, Choi EJ, et al. The impact of blood flow rate during hemodialysis on all-cause mortality. Korean J Intern Med 2016;31:1131-9.  Back to cited text no. 18
    
19.
Borzou SR, Gholyaf M, Zandiha M, Amini R, Goodarzi MT, Torkaman B. The effect of increasing blood flow rate on dialysis adequacy in hemodialysis patients. Saudi J Kidney Dis Transpl 2009;20:639-42.  Back to cited text no. 19
[PUBMED]  [Full text]  
20.
Kim YO, Song WJ, Yoon SA, et al. The effect of increasing blood flow rate on dialysis adequacy in hemodialysis patients with low Kt/V. Hemodial Int 2004;8:85.  Back to cited text no. 20
    
21.
Thompson S, Manns B, Lloyd A, Hemmelgarn MacRae J, Klarenbach S, et al. Impact of using two dialyzers in parallel on phosphate clearance in hemodialysis patients: A randomized trial. Nephrol Dial Transplant 2017;32: 855-61.  Back to cited text no. 21
    
22.
Gutzwiller JP, Schneditz D, Huber AR, Schindler Garbani E, Zehnder CE. Increasing blood flow increases kt/V(urea) and potassium removal but fails to improve phosphate removal. Clin Nephrol 2003;59:130-6.  Back to cited text no. 22
    
23.
Kerr PG, Lo A, Chin Mm, Atkins RC. Dialyzer performance in the clinic: Comparison of six low-flux membranes. Artif Organs 1999;23:817-21.  Back to cited text no. 23
    

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Correspondence Address:
Dr. Hicham Rafik
Department of Nephrology, Dialysis and Renal Transplantation, Mohammed V Military Hospital, Faculty of Medicine, Mohammed V-Souissi University, Rabat
Morocco
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DOI: 10.4103/1319-2442.239654

PMID: 30152424

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