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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2009  |  Volume : 20  |  Issue : 6  |  Page : 1023-1029
Increasing dialysate flow rate increases dialyzer urea clearance and dialysis efficiency: An in vivo study

Misr University for Science and Technology, Systems and Biomedical Engineering Department, 6th of October City, Egypt

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Date of Web Publication27-Oct-2009


Clearance of urea depends on the dialysis solution flow rate as well. A faster dialysis solution flow rate increases the efficiency of diffusion of urea from blood to dialysate. An in vivo study was used in order to examine the effect of increasing dialysate flow rate (Q D ) on dialyzer urea clearance and dialysis efficiency expressed as Kt/V and URR. Group assignment was at the patient level rather than the facility level. The study subjects consisted of 138 hemodialysis patients on 3­times-per-week dialysis regimens. One way ANOVA test, Student's t test and Logistic regression analysis were used to analyze the data. Statistically significant increase in Kt/V and URR was noted as the dialysate flow increased from 500 to 800 mL/min when a moderate efficiency dialyzer with large surface area (1.6 m 2 ) and high flux high efficiency dialyzers were used (P< 0.05). For moderate efficiency dialyzers with large surface area, Kt/V increased by 5.86% (P= 0.022628) and URR increased by 4.31% (P= 0.02263). Low efficiency and small surface area (1.2 m 2 and 1.3 m 2 ) dialyzer did not show an improvement in Kt/V or URR with increase in dialysate flow rate. Increasing Q D from 500 to 800 mL/min is associated with a statistically significant increase in Kt/V, URR and dialyzer clearance in moderate efficiency low flux and high efficiency high flux dialyzers. Hemodialysis with Q D of 800 mL/min should be considered in selected patients not achieving adequacy despite extended treatment times and optimized blood flow rates.

How to cite this article:
Azar AT. Increasing dialysate flow rate increases dialyzer urea clearance and dialysis efficiency: An in vivo study. Saudi J Kidney Dis Transpl 2009;20:1023-9

How to cite this URL:
Azar AT. Increasing dialysate flow rate increases dialyzer urea clearance and dialysis efficiency: An in vivo study. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2023 Jan 29];20:1023-9. Available from: https://www.sjkdt.org/text.asp?2009/20/6/1023/57258

   Introduction Top

Accurate prediction of dialyzer urea clearance during hemodialysis is essential when prescri­bing therapy using urea kinetic modeling. [1],[2] Small solute removal is primarily obtained by diffusion. Convection represents an additional mechanism that is mostly important for larger molecules. [3],[4],[5] The efficiency of a hemodialyzer is therefore dependent on its ability to facilitate the diffusion process. [6],[7],[8] Diffusion is affected by blood and dialysate flow rates, temperature, surface area of the dialyzer, and thickness of the membrane. Assuming all other factors are cons­tant, the diffusion process is basically dependent on the concentration gradient between blood and dialysate. [9],[10] This is strongly affected by the blood and dialysate flow rates and by the distri­bution of the countercurrent flows in their rela­tive compartments. It is evident that any possi­ble mismatch between blood and dialysate flow distributions can create a significant reduction in the efficiency of the filter. [9] The dialyzer mass transfer area coefficient for urea, KoA, is a mea­sure of dialyzer efficiency in clearing urea and solutes of similar molecular weight. [1] The KoA is the maximum theoretical clearance of the dia­lyzer in milliliters per minute for a given solute at infinite blood and dialysate flow rates. For any given membrane, KoA will be proportional to the surface area of the membrane in the dia­lyzer, although there is a drop-off in the gain in KoA as membrane surface area becomes very large. [1] Dialyzers with KoA values less than 500 mL/min should be used only for "low-efficiency" dialysis or for small patients. Dialyzers with KoA values of 500-700 mL/min represent mode­rate-efficiency dialyzers, useful for routine the­rapy. Dialyzers with KoA values greater than 700 mL/min are used for "high-efficiency" dia­lysis, in a large size patient when a 4 hour dialysis session is not adequate. In practice, whereas the KoA of a dialyzer does not change at various blood flow rates, the KoA does increase substantially when dialysate flow rate is increased from 500 to 800 mL/min. [11],[12],[13],[14],[15],[16] This apparent increase in the surface area of the dia­lyzer at high dialysate flow rate is probably due to better penetration of the dialysate into the hollow-fiber bundle, resulting in an expansion of the dialyzer effective surface area and increa­sing in dialysis efficiency. [17],[18] In the present study, we determined urea clearance and KoA for four different dialyzer models under identi­cal in vitro and in vivo tests conditions then determined the dependence of urea KoA and dialysis efficiency on the dialysate flow rates.

   Methodology Top

The study subjects consisted of 138 maintenance hemodialysis patients (mean age 50.51 ± 15.12, 72 male, 66 female). The overall study period was 3 months. No subjects dropped out of the study. Demographic and co-morbidity data were obtained, as well as information on the dialysis prescription. All dialysis patients at this centre have a detailed clinical summary of their medi­cal history on the dialysis chart, which has been written by the primary nephrologist and is up­dated regularly. The presence of diabetes mellitus (DM), coronary artery disease (CAD), left ven­tricular (LV) dysfunction and peripheral vascu­lar disease (PVD) was ascertained by reviewing this summary. In addition, patients were also considered to have DM if they were on insulin or oral hypoglycaemic agents. Patients were also considered to have CAD if they had a known positive stress test or coronary angiogram or previous coronary artery angioplasty or bypass grafting. All dialysis treatments over the pre­ceding 3 months were reviewed for volume of blood processed (VBP), treatment duration, dia­lysis shift, level of nursing care, target weight, ultrafiltration volume, hypotension (defined as any documented systolic blood pressure <100 mmHg), dialyzer clotting, Kt/V and URR. To evaluate the effect of increasing dialysate flow rate on dialyzer clearance, KoA and dialysis effi­ciency at constant blood flow rate all patients were sub-grouped to: 25 patients (18.12%) dia­lyzed with 1.2m 2 cellulosynthetic low flux-low efficiency dialyzer (homophone), 50 patients (36.23%) dialyzed with 1.3 m 2 low flux-moderate efficiency polysulfone dialyzer, 30 patients (21.74%) dialyzed with 1.6 m 2 low flux-mode­rate efficiency polysulfone dialyzer and 33 pa­tients (23.91%) dialyzed with 1.8 m 2 high flux­high efficiency polysulfone dialyzer [Table 1]. VBP on dialysis was recorded after each session directly from the hemodialysis machine. VBP represents the product of the blood flow calcu­lated from the calibrated blood pump, integrated over the total time of the dialysis session. Ave­rage blood flow per session was calculated by dividing the VBP by the treatment duration re­corded for each session. The URR was calcula­ted using the formula: (Urea pre-Urea post/Urea pre Χ 100%). [19] The single-pool Kt/V (Kt/V s p) was determined from the Daugirdas second ge­neration formula [20] The pre-dialysis urea level was drawn immediately prior to hemodialysis initiation whereas the post-dialysis urea was drawn 5 min after the patient's blood had been reinfused. This procedure does not have a direct effect on the VBP for that session. The dialysis treatment characteristics are summarized in [Table 2]. Patients had dialysis three times a week, in 4 hour sessions, with a pump arterial blood flow of 300 mL/min, and flow of the dialysis bath of 500-800 mL/min. Dialysate temperature in all treatments was 36-37°C. The dialysate consisted of the following constituents: sodium 141 mmol/ L, potassium 2.0 mmol/L, calcium 1.3 mmol/L, magnesium 0.2 mmol/L, chloride 108.0 mmol/L, acetate 3.0 mmol/L and bicarbonate 35.0 mmol/L. A Fresenius model 4008B dialysis machine equipped with a volumetric ultrafiltration con­trol system was used in each dialysis. Fluid re­moval was calculated as the difference between the patients' weight before dialysis and their tar­get dry weight. Pre-dialysis body weight, blood pressure and pulse rate were measured before ingestion of food and drink.

The in-vitro clearance data were determined according to the dialyzer specification sheet at blood flow rate 300 mL/min and two dialysate flow rates 500 mL/min and 800 mL/min, where­as specific dialysis prescriptions such as treat­ment time and blood flow rate [Q B ], were kept constant. The ultrafiltration flow rate was also kept constant at zero during each experiment. Two blood samples were drawn from the arterial blood line at the dialyzer inlet and venous blood line at dialyzer outlet to determine the dialyzer in-vivo clearance. Both blood side and dialysate side urea clearances were calculated using stan­dard formula. [2] Blood side clearance was calcu­lated as (Cbi-Cbo) Χ (Qb/Cbi), and dialysate side clearance was calculated as Cdo Χ (Qd/Cbi), where Cbi denotes the urea nitrogen concentration in the blood inlet (arterial), Cbo denotes the urea nitrogen concentration in the blood outlet (ve­nous), and Cdo denotes the urea nitrogen con­centration in the dialysate outlet. Urea KoA was calculated from the mean of the blood and dia­lysate side urea clearances (Kd) using the follo­wing equation for countercurrent blood and dia­lysate flows: [21]

Where Ko is the mass transfer coefficient of dialyzer, A is the surface area, QB is the blood flow rate, QD is the dialysate flow rate, ln is the natural logarithm and Kd is the mean of blood and dialysate side urea clearance. The average values of blood and dialysate side clearance were taken as a reference for each patient. When mass balance error was greater than 5% the test was discarded and repeated. Delivered dose of dialysis, assessed by single-pool Kt/V (Kt/Vsp), urea reduction ratio (URR) and dialyzer in-vivo urea clearance rate were calculated at the two levels of dialysate flow rate and the four types of dialyzers used in the study. Statistical ana­lysis was performed using SPSS 14.0 and NCSS 2007 software packages. Mean errors relative to reference values were compared by one way ANOVA test. The Student's t test was used for both paired and non-paired data. P values < 0.05 were considered as statistically significant. Confidence intervals on the discrepancy bet­ween different estimates of the same parameter are calculated as Bland-Altman 95% limits of agreement.

   Results Top

[Table 3] summarizes the effect of increasing dialysate flow rate on dialyzer clearance, KoA and dialysis efficiency at constant blood flow rate. Increasing Q D from 500 to 800 mL/min was associated with a statistically significant increase in KoA and in-vivo urea clearance (Kt/V and URR) for all types of dialyzers, except for Type I and Type II dialyzers where Kt/V and URR didn't change significantly. [Table 4] shows the percentage change in different parameters of clearance when dialysate flow rate was in­creased. [Figure 1],[Figure 2],[Figure 3],[Figure 4] demonstrate the effect of dialysate flow rate on in-vivo urea clearance, KoA, Kt/V and URR.

   Discussion Top

Main findings in our study are that increasing dialysate flow rate to 800 mL/min from usual 500 mL/min significantly improves the Kt/V and URR in moderate and high efficiency dialyzers only. Hemodialysis remains the major modality of renal replacement therapy. Since the 1970s the drive for shorter dialysis time with high urea clearance rates has led to the development of high-efficiency hemodialysis. In the 1990s, certain biocompatible features and the desire to remove amyloidogenic (32-microglobulin has led to the popularity of high-flux dialysis. During the 1990s, the use of high-efficiency and high­flux membranes has steadily increased and use of conventional membrane has declined. [22] In 1994, a survey by the Centers for Disease Con­trol showed that high-flux dialysis was used in 45% and high-efficiency dialysis in 51% of dia­lysis centers in United States. [22] Despite the in­creasing use of these new hemodialysis moda­lities the clinical risks and benefits of high­performance therapies are not well defined. In the literature published over the past 10 years the definitions of high-efficiency and high-flux dialysis have been confusing. Currently, treat­ment quantity is not only defined by time but also by dialyzer characteristics, i.e., blood and dialysate flow rates. In the past, when the effi­ciency of dialysis and blood flow rates tended to be low, treatment quantity was satisfactorily defined by time. Today, however, treatment time is not a useful expression of treatment quantity because efficiency per unit time is highly varia­ble. The dialyzer mass transfer-area coefficient characterizes the permeability of the mass trans­fer barrier between the blood and dialysate path­ways of a hemodialyzer. Increasing the blood or dialysate flow rate decreases the thickness of the respective stagnant fluid layer. [12] This study investigated in vitro and in vivo performance of four types of dialyzers with a special focus on the effect of dialysate flow rate on urea clea­rance and dialysis efficiency over the dialysate flow rate ranges from 500 to 800 mL/min. A stan­dard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from solute concen­trations in the input and output flows on both the blood and dialysate sides. In vivo urea clearance and KoA values, calculated from the mean of the blood and dialysate side clearances, increased (P< 0.01) with increasing Q D over the entire range studied. These data show that changes in Q D alter small solute clearances greater than pre­dicted assuming a constant rate of 500 mL/min. The increase in urea KoA with increasing dialy­sate flow rate suggests that the dialysate stagnant fluid layer provides a significant resistance to urea transfer. It is also possible, however, that the increase in urea KoA with increasing dia­lysate flow rate results from an improved distri­bution of flow in the dialysate compartment. [9] A flow rate of 800 mL/min will increase urea clearance by about 12%, Kt/V by about 6% and URR by about 5% when a high-efficiency dialyzer is used. These increases in urea clea­rance and single pool Kt/V are substantial and would permit significant increases in dialysis dose as assessed by urea kinetics given a fixed treatment time.

   Acknowledgement Top

The author thanks all medical staff at the neph­rology department in Ahmad Maher Teaching Hospital, Cairo, Egypt for their invaluable sup­port during the course of this study. Special thanks are sent to the maintenance department inside the hospital that gave me the computa­tional aids and technical support to finish this study.

   References Top

1.Daugirdas JT. Chronic hemodialysis prescription: a urea kinetic approach. In: Daugirdas JT. Ing TS. eds. Handbook of dialysis. 2nd ed. Boston: Little Brown. 1994: 92-120.  Back to cited text no. 1      
2.Sargent JA, Gotch FA: Principles and biophysics of dialysis, in Replacement of Renal Function by Dialysis (4 th ed), Jacobs C, Kjellstrand CM, Koch KM, Winchester JF. Eds. Dordrecht, Kiuwer Academic, 1996, pp 34-102.  Back to cited text no. 2      
3.Galach M, Ciechanowska A, Sabalinska S, Waniewski J, Wojcicki J, Werynskis A. Impact of convective transport on dialyzer clearance. J Artif Organs 2003;6(1):42-8.  Back to cited text no. 3      
4.Locatelli F, Manzoni C, Di Filippo S. The im­portance of convective transport. Kidney Int 2002;61:115-20.  Back to cited text no. 4      
5.Jaffrin YM. Convective Mass Transfer in Hemo­dialysis. Artif Organs 1995;19:1162-71.  Back to cited text no. 5      
6.Jaffrin MY, Ding LH, Laurent JM. Simulta­neous convective and diffusive mass transfers in hemodialyzer. ASME J Biomech Eng 1990;112: 212-9.  Back to cited text no. 6      
7.Sigdell JE. Calculation of combined diffusive and convective mass transfer. Int Artif Organs 1982;5:361-72.  Back to cited text no. 7      
8.Gostoli C, Gatta A. Mass Transfer in a Hollow Fiber Dialyzer. J Membr Sci 1980;6:133-48.  Back to cited text no. 8      
9.Vander Velde C, Leonard EF: Theoretical assess­ment of the effect of flow maldistributions on the mass transfer efficiency of artificial organs. Med Biol Eng Comput 1985;23:224-9.  Back to cited text no. 9      
10.Hoenich N, Ronco C: Dialyzers evaluation. In: Replacement of Renal Function by Dialysis, Winchester J, Koch K, Jacobs C, Kjiellestrand C. eds. Dordrecht, Kluwer Academic Publishers, 1996; 256-270.  Back to cited text no. 10      
11.Clark WR, Shinaberger JH. Effect of Dialysate­side Mass Transfer Resistance on Small Solute Removal in Hemodialysis. Blood Purif 2000;27: 260-3.  Back to cited text no. 11      
12.Leypoldt JK, Cheung A, Agodoa L, Daugirdas J, Greene T, Keshaviah P. Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. Kidney Int 1997;51: 2013-7.  Back to cited text no. 12      
13.Leypoldt JK, Cheung A. Effect of low dialysate flow rates on hemodialyzer mass transfer area coefficients for urea and creatinine. Home HD Int 1999;3:51-4.  Back to cited text no. 13      
14.Leypoldt JK. Effect of Increasing Dialysate Flow Rate on KoA and Dialyzer Urea Clearance. Semin Dial 1998;11(3):195-6.  Back to cited text no. 14      
15.Ward R, Ouseph R. Increasing dialysate flow rate increases the urea mass transfer coefficient: membrane area product during clinical dialysis (abstract). J Am Soc Nephrol 1999;10:199A.  Back to cited text no. 15      
16.Choong L, Leypoldt JK, Cheung A. Dialyzer mass transfer-area coefficients during clinical hemodialysis are dependent on both blood flow and dialysate flow rates (abstract). J Am Soc Nephrol 1999;10:189A.  Back to cited text no. 16      
17.Hauk M, Kuhlmann M, Riegel W, Kohler H. In vivo effects of dialysate flow rate on Kt/V in maintenance hemodialysis patients. Am J Kidney Dis 2000;35:105-11.  Back to cited text no. 17      
18.Leypoldt JK, Cheung AK. Increases in mass transfer area coefficients and urea Kt/V with increasing dialysate flow rate are greater for high-flux dialyzers. Am J Kidney Dis 2001;38: 575-9.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]  
19.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. 19      
20.Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 1993;4 (5):1205-13.  Back to cited text no. 20      
21.Michaels AS. Operating parameters and perfor­mance criteria for hemodialyzers and other membrane-separation devices. Trans Am Soc Artif Intern Oigans 1966;12:387-92.  Back to cited text no. 21      
22.Tokars JI, Alter MJ, Miller E, et al. National surveillance of dialysis associated disease in the United States: 1994. ASAIO J 1997;43:108-19.  Back to cited text no. 22  [PUBMED]    

Correspondence Address:
Ahmad Taher Azar
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 2], [Table 4]

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