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ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 4  |  Page : 677-682

Comparative study of the effect of high-flux versus low-flux dialysis membranes on metabolic abnormalities in chronic hemodialysis patients


1 Department of Internal Medicine, Faculty of Medicine, Menoufiya University, Al-Menoufiya, Egypt
2 Department of Nephrology, Benha Teaching Hospital, Benha, Egypt

Date of Submission30-Dec-2013
Date of Acceptance14-Apr-2014
Date of Web Publication22-Jan-2015

Correspondence Address:
Abd El Samad Sobhy Abou El Nasr
Garawan, El Bagour, Al-Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.149667

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  Abstract 

Objective
The aim of the study was to compare the effect of permeability of low-flux versus high-flux dialysis membranes on control of metabolic abnormalities in chronic hemodialysis patients.
Background
End-stage renal disease is associated with multiple physiological and metabolic disturbances, including hypertension, anemia, hyperparathyroidism, dyslipidemia, malnutrition, and other serious problems that markedly and negatively affect prognosis and the quality of life of uremic patients. New dialyzers have large pores and they are more compatible than pure cellulose membranes; thus, they provoke less inflammatory reaction and are more efficient in removal of uremic toxins.
Materials and methods
Forty adult patients on regular hemodialysis were enrolled in a prospective study. Low-flux polysulfone membranes were used for at least 6 months and then patients were switched to use high-flux polysulfone membranes for 1 month. Serum electrolytes and intact parathyroid hormone (PTH) before and after dialysis were compared before and after changes in dialysis membrane.
Results
At the end of the 1-month use of high-flux filters, a highly significant increase in the mean of hemoglobin levels from 9.50 ± 1.08 to 10.29 ± 1.04 (P = 0.001) was evident. Postdialysis mean arterial blood pressure decreased significantly after use of high-flux dialysis (P = 0.002). There were highly significant decreases in predialysis blood urea nitrogen, phosphorus, sodium, and potassium after the use of high-flux filters. Predialysis intact PTH level (415.96 ± 226.72 ng/dl) showed a significant decline (P < 0.05) compared with the predialysis intact PTH (312.28 ± 191.98 ng/dl) with low-flux membranes.
Conclusion
High-flux dialysis membranes are more efficient in control of metabolic abnormalities in chronic hemodialysis patients than low-flux membranes.

Keywords: Dialysis, end-stage renal disease, metabolic abnormalities, parathyroid hormone


How to cite this article:
El Arbagy AR, Koura MA, El Barbary HS, Abou El Nasr AE. Comparative study of the effect of high-flux versus low-flux dialysis membranes on metabolic abnormalities in chronic hemodialysis patients. Menoufia Med J 2014;27:677-82

How to cite this URL:
El Arbagy AR, Koura MA, El Barbary HS, Abou El Nasr AE. Comparative study of the effect of high-flux versus low-flux dialysis membranes on metabolic abnormalities in chronic hemodialysis patients. Menoufia Med J [serial online] 2014 [cited 2020 Feb 26];27:677-82. Available from: http://www.mmj.eg.net/text.asp?2014/27/4/677/149667


  Introduction Top


A number of therapies and technologies have been reported to improve health-related quality of life in patients with chronic kidney failure; however, patients report that they remain substantially burdened by limited physical functioning and by dialysis-related symptoms [1].

Chronic kidney disease (CKD) is associated with many kinds of metabolic changes caused by the kidney disease and also attributable to dialysis treatment. Phenomena such as accumulation or deficit of various substances and dysregulation of metabolic pathways combine in the pathogenesis of these changes. In the process of accumulation, decreased urinary excretion plays a crucial role and leads to retention of metabolites (e.g. creatinine, urea, electrolytes, water). The increased formation of metabolites through catabolic processes and alternative metabolic pathways also exerts an influence. This deficit of some important substances in CKD can be caused by deficient intake in the diet, impaired intestinal absorption, or increased losses during dialysis sessions. Disturbed synthesis of some crucial metabolic regulators (e.g. erythropoietin, active vitamin D) in kidneys also plays an important role [2]. Health-related quality of life has been associated with nutritional outcomes, hospitalizations, and survival in patients with end-stage renal disease (ESRD). The quality of life in ESRD patients on dialysis is also dependent on the quality of dialysis [3].

Three general types of dialysis membranes are available at present: unmodified cellulose (low flux; namely 'bioincompatible' membranes), modified/regenerated cellulose (low flux or high flux; namely, 'relatively biocompatible'), and synthetic (low flux or high flux; namely 'relatively biocompatible') [4].

The choice of a dialysis membrane should take into account the following: biocompatibility of the material toward leukocytes and complement activation; blood volume priming requirement, which is membrane area related; and permeability, determined in the simplest way by two characteristics of hydraulic permeability and molecular permeability determined at least by molecular weight of the molecule considered [5].

Uremic toxins are classified into three groups: small (<500 Da) water-soluble molecules such as urea, sodium, and phosphate, which are rapidly produced in extracellular compartment and are efficiently removed by most filters; middle-sized (500-40 000 Da) water-soluble molecules such as b2-microglobulin, parathyroid hormone (PTH), some cytokines (interleukin-6 and tumor necrosis factor) that require optimized filter design and convection for removal; and small (<500 Da) but protein-bound molecules that are poorly removed with traditional dialysis [6].

In fact, low-flux membranes do not remove middle-sized molecule toxin but highly permeable membranes are efficient in removal of both small nonprotein-bound and middle-sized uremic toxins [7].


  Materials and methods Top


This study was conducted on 40 adult patients with ESRD under regular hemodialysis in Hemodialysis Unit, Benha Teaching Hospital during the period from January 2013 to August 2013. There were 20 male patients and 20 female patients. All patients with minimum dialysis duration of 6 months were included. Patients who had parathyroidectomy with or without replacement therapy were excluded.

All patients were on conventional hemodialysis, 4-h sessions, three times per week using hemodialysis machines (4008B; Fresenius Medical Care) with low-flux polysulfone filters (Fresinius F6). The standard dialysis bath consisted of sodium, 103 mEq/l; potassium, 2 mEq/l; calcium, 1.75 mmol/l; and bicarbonate, 35 mEq/l. All patients were switched to high-flux polysulfone filters (Fresinius F6) for 1-month duration without changing any of the other dialysis prescription parameters (except for ultrafiltration to reach their optimal dry weight, which is defined as the postdialysis body weight below which the patients developed symptomatic hypotension or muscle cramps in the absence of edema).

Serum electrolytes and intact PTH were compared before and after changing the dialysis membranes. Moreover, the doses of vitamin D analogs and phosphate binders were kept constant through the study. Thereafter, samples were taken before and after session.

Sampling

Samples were collected from arteriovenous fistula into tubes at room temperature and centrifuged within 1 h. The serum was stored at -70°C before analysis.

Methods

  1. Blood urea.
  2. Serum creatinine (modified rate Jaffe method).
  3. Complete blood count.
  4. Serum sodium and potassium were measured.
  5. Total serum calcium was measured according to the Arsenazo method [8].
  6. Serum inorganic phosphorus was measured by phosphomolybdate complex method [9].
  7. Human PTH.


The DIAsource hPTH-EASIA (hPTH-EASIA Kit; DIAsource, Rue du Bosquet, Belgium) is a solid-phase enzyme amplified sensitivity immunoassay performed on microtiter plates. Calibrators and samples react with the capture polyclonal antibodies (goat anti 1-34 PTH fragment) coated on microtiter well. After incubation, the excess of antigen is removed by washing.

Thereafter, monoclonal antibodies (mouse anti 44-68 PTH fragment) labeled with horseradish peroxidase are added. After an incubation period allowing the formation of a sandwich, the microtiter plate is washed to remove unbound enzyme-labeled antibody. Bound enzyme-labeled antibody is measured through a chromogenic reaction.

The chromogenic solution (TMB) is added and incubated. The reaction is stopped with the addition of stop solution and the microtiter plate is then read at the appropriate wavelength. The amount of substrate turnover is determined colorimetrically by measuring the absorbance, which is proportional to the PTH concentration.

A calibration curve is plotted and PTH concentration in samples is determined by interpolation from the calibration curve.

Serum albumin was assayed according to the Bromocresol Green method [10].

Statistical methodology

The data collected were tabulated and analyzed by statistical package for the social science software (SPSS) statistical package, version 20 on IBM compatible computer.


  Results Top


Sociodemographic characteristics of the studied patients are shown in [Table 1]. Postdialysis mean arterial blood pressure decreased significantly after use of high-flux dialysis (P = 0.002) [Table 2] and [Figure 1] [Table 3]. There were highly significant decreases in predialysis blood urea nitrogen, sodium, and potassium at the end of the 1-month after the use of high-flux filters [Table 4]. The predialysis values reflected the real patient status rather than immediate postdialysis values reflecting the permeability coefficient of the dialyzer membrane.
Figure 1: Comparison between predialysis iPTH for patients with low-flux and high-flux dialysis membranes. iPTH, intact parathyroid hormone.

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Table 1: Sociodemographic characteristics of the studied patients

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Table 2: Distributions of patients according to cause of ESRD

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Table 3: Comparison between predialysis and postdialysis mean arterial blood pressure for patients with low-flux and high-flux dialysis membranes

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Table 4: Comparison between predialysis PTH, Hg, albumin, serum electrolytes, creatinine, and BUN for patients with low-flux and high-flux dialysis membranes

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Although creatinine was efficiently removed by both filter types, still there was a significant decline in predialysis serum creatinine at the end of the 1-month after the use high-flux filter (P = 0.04). A highly significant increase was observed in the mean hemoglobin levels from 9.50 ± 1.08 to 10.29 ± 1.04 (P = 0.001) after use of high-flux filters [Table 4]. The mean postdialysis level of serum phosphorus showed a significant decline than the predialysis levels with low-flux filters and a highly significant decline than predialysis level in high-flux ones (postdialysis levels, 5.90 ± 0.42 and 3.80 ± 0.36 mg/dl, respectively) [Table 5].
Table 5: Comparison between predialysis and postdialysis PTH, serum albumin, electrolytes, creatinine, and BUN for patients with low-flux and high-flux dialysis membranes

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The mean postdialysis levels of serum calcium were significantly higher than the predialysis levels for both low-flux and high-flux filters (postdialysis levels, 8.54 ± 0.84 and 8.58 ± 0.87 mg/dl, respectively). In contrast, there was no significant change in predialysis values of serum albumin or serum calcium after using high-flux filters [Table 4].

At the end of the 1-month use of high-flux filters, predialysis intact PTH level showed a significant decline (P = 0.002) compared with the predialysis level using low-flux filters at the start of the study (312.28 ± 191.98 vs. 415.96 ± 226.72 pg/ml, respectively). Postdialysis levels of intact PTH showed a highly significant decline than predialysis level after use of high-flux filter but not after the use of the low-flux one.


  Discussion Top


CKD is associated with many kinds of metabolic changes caused by the kidney disease and also attributable to dialysis treatment. Phenomena such as accumulation or deficit of various substances and dysregulation of metabolic pathways combine in the pathogenesis of these changes. In the process of accumulation, decreased urinary excretion plays a crucial role and leads to retention of metabolites (e.g. creatinine, urea, electrolytes, water). The increased formation of metabolites through catabolic processes and alternative metabolic pathways also exerts an influence. This deficit of some important substances in CKD can be caused by deficient intake in the diet, impaired intestinal absorption, or increased losses during dialysis sessions. Disturbed synthesis of some crucial metabolic regulators (e.g. erythropoietin, active vitamin D) in kidneys also plays an important role [2].

In our study, mean arterial blood pressure declined significantly after the use of high-flux membranes but not after the use of low-flux ones, and this may be related to significant ultrafiltration occurred with high-flux dialyzers.

In a study by Li et al. [11] on 30 patients undergoing dialysis for at least 2 years with a low-flux dialyzer switched to the FX60 dialyzer for 3 years, the mean arterial blood pressure decreased significantly after the switch to high-flux dialysis membranes.

In a study by Momeni et al. [12], blood pressure before and after dialysis with a low-flux or a high-flux membrane did not show statistically significant differences (P > 0.05).

In a prospective crossover study performed by Takenaka et al. [13] on 10 adult hemodialysis patients with low-flux and high-flux dialyzers, the mean blood pressure remained unchanged in either state.

In our study, there was a highly significant increase in the mean hemoglobin levels from 9.50 ± 1.08 to 10.29 ± 1.04 after 1 month of use of high-flux dialysis (P = 0.001).

In a study by Ayli et al. [14], significant increase was observed in the mean hemoglobin after use of high-flux dialysis. However, in a study by Schneider et al. [15], after 52 weeks, the low-flux and the high-flux groups did not differ with respect to hemoglobin (P = 0.62).

The increase in hemoglobin level in our study may be attributed to potential benefits of high-flux membranes in reduction of erythropoietin resistance. This might be related to reduction in the level of PTH among these patients, as hyperparathyroidism is usually listed as one of possible reasons for impaired response to recombinant human erythropoietin (rHuEPO) in patients with renal disease [16].

In this study, there was a highly significant decline of serum sodium, potassium, creatinine, and blood urea nitrogen levels after the use of high-flux filters. Although they were significantly removed by low-flux filters for being water soluble and with small molecular weight (e.g. urea is 60 Da), still they were more efficiently eliminated by the use of increasingly permeable high-flux dialysis membranes with excellent blood purification. High-flux filters with large pore sizes are efficient in removal of toxins with medium weight but in contrast, other smaller substances may be markedly decreased [17].

In our study, there was no statistical significant difference between use of low-flux dialysis and high-flux dialysis with respect to serum calcium, but there was a highly significant reduction in phosphorus level.

In a study by Ayli et al. [18], there was no statistical significant difference between the high-flux dialyzer group and the low-flux group with respect to calcium, but there was significant reduction in phosphorus level.

In study by Makar et al. [19], there was no statistical significant difference between use of low-flux dialysis and high-flux dialysis with respect to calcium, but there was statistical significant decrease in serum phosphorus and alkaline phosphatase after use of high-flux dialysis compared with low-flux dialysis.

There was no significant change in serum albumin after the use of high-flux filters. According to Vanholder et al. [20], middle-sized molecules were defined as any solute with molecular weights between 500 and 40 000 Da. Albumin, with a molecular weight of 65 000 Da, is considered a relatively too large molecule to be filtered by both membrane types.

Krieter and Canaud [17] found that highly permeable membranes may increase albumin loss and lead to harmful consequences; however, they could not estimate accurately the extent of albumin loss through highly permeable dialysis membranes. Lindsay and Spanner [21] noted that switching from low-flux to high-flux dialysis membranes did not increase the protein catabolic rate as previously found through using some high-flux membranes such as the AN69 dialyzer; instead, a significant increase in predialysis serum albumin levels was observed [22]. It was further postulated that this may be the result of improved dietary intake and potential explanation involving the removal of plasma substances that inhibit appetite, such as the putative factor in uremic plasma, leptin (16 kD), and other peptides [23].

In accordance with the present findings, in the study by Makar et al. [19], there was no significant change in serum albumin after use of high-flux filters. In addition, in a study by Ayli et al. [18], there was no statistical significant difference between the low-flux and high-flux groups with respect to albumin level.

In our study, we found postdialysis highly significant decline in intact PTH after the use of high-flux membranes but not after the use of low-flux ones. In addition, predialysis intact PTH level showed a highly significant decline compared with the predialysis intact PTH with low-flux membranes at the start of the study.

In a study by Makar et al. [19] on 44 pediatric hemodialysis patients switched from low-flux dialysis to high-flux dialysis for 3 months, postdialysis levels of intact PTH were significantly lower than predialysis levels after use of high-flux filter but not after the use of the low-flux one. At the end of 3 months of use of high-flux filters in a study by Makar et al. [19], predialysis intact PTH level showed a highly significant decline compared with the predialysis intact PTH with low-flux membranes at the start of the study.

In a study by Balducci and colleagues, different PTH behavior during hemodialysis with different types of dialysis membranes was reported in 12 adult dialysis patients with secondary hyperparathyroidism. Each hemodialysis modality lasted 2 weeks for study period of 6 weeks. The first treatment consisted of standard bicarbonate dialysis with low-flux polysulfone, followed by acetate-free biofiltration with high-flux polysulfone or with polyacrylonitrile-AN69. Intact PTH was assayed on the blood and dialysate samples to calculate intact PTH adsorption. The results showed that polyacrylonitrile-AN69 and high-flux polysulfone induce a significantly larger decrease in PTH serum levels as compared with low-flux polysulfone, particularly in the first half of the dialysis session [24].


  Conclusion Top


High-flux dialysis membranes are more efficient than low-flux membranes in removal of uremic toxins and in minimizing the consequences of metabolic abnormalities associated ESRD.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

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24.
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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