High-volume pre-dilution on-line hemodiafiltration is the adequate blood purification method from the viewpoint of amino acid nutrition
Renal Replacement Therapy volume 8, Article number: 51 (2022)
We compared amino acid leakage among high-volume pre-dilution on-line hemodiafiltration (Pre O-HDF), hemodialysis (HD), and post-dilution on-line hemodiafiltration (Post O-HDF).
Subjects and methods
The subjects were 9 patients. For HD, the total dialysate flow rate was established as 500 mL/min. For high-volume Pre O-HDF, it was established as 600 mL/min, under a replacement fluid volume of 90 L. For Post O-HDF, it was established as 600 mL/min, under a replacement fluid volume of 10 L. In both procedures, the duration of treatment was 4 h, and the blood flow volume was 200 mL/min. We compared the leakages of total amino acid, non-essential amino acid, and essential amino acid, clear spaces (CSs), β2-microglobulin (β2-MG) reduction rate, Kt/V for urea, and albumin leakage among the three procedures.
Amino acid leakages after high-volume Pre O-HDF were significantly lower than HD and Post O-HDF. The CSs after high-volume Pre O-HDF were significantly lower than Post O-HDF. The β2-MG reduction rate after high-volume Pre O-HDF was significantly lower than Post O-HDF. The Kt/V for urea was not significantly different. Albumin leakages were below the detection limit (< 1 g) in the three procedures.
Under the treatment conditions we performed this time, high-volume Pre O-HDF reduces amino acid leakage in comparison with HD and Post O-HDF. High-volume Pre O-HDF is a therapeutic mode that suppresses amino acid leakage.
According to the 2018 Annual Dialysis Data Report by the Japanese Society for Dialysis Therapy, the mean age of hemodialysis patients as of the end of 2018 was 69.99 years. The mean age has been increasing each year, and the age-group accounting for the highest percentage of patients was 70–74 years for both men and women . Prevention of sarcopenia and frailty in aging hemodialysis patients has become the most pressing challenge to tackle in order to preserve patients’ quality of life and allow them to enjoy a rich life in their old age [2,3,4]. This challenge must be approached from the perspective of not only diet and exercise therapy but also blood purification therapy. In fact, patients on hemodialysis or peritoneal dialysis suffer a serious decline in nutritional status due to loss of amino acids and proteins through renal replacement therapy, as has been described in guidelines [5, 6].
To address this issue in blood purification therapy, we try to preserve nutrition by using high-volume pre-dilution on-line hemodiafiltration (HDF) (high-volume Pre O-HDF), which uses a hemodiafilter that allows little albumin leakage and inhibits amino acid leakage by lowering the rate of diffusion of low molecular weight amino acids. Naturally, this method is also beneficial for elderly diabetic patients on hemodialysis because it stabilizes blood pressure during dialysis. However, the degree of amino acid (AA) (micromolecular substance) leakage remains to be clarified. In this study, we compared AA leakage among high-volume Pre O-HDF, hemodialysis (HD), and post-dilution on-line hemodiafiltration (Post O-HDF).
We sought to determine the optimal method to suppress amino acid losses during three types of dialysis (high-volume Pre O-HDF, HD, and Post O-HDF).
The subjects were 9 patients who had received maintenance dialysis in our hospital (7 males, including 4 diabetics, mean age 71.4 ± 2.5 years, mean duration of dialysis 9.3 ± 7.1 years) (Table 1). Table 2 shows the patient's general condition (serum albumin, pre-dialysis amino acid concentration, body weight) (Table 2). For HD, the total dialysate flow rate was established as 500 mL/min, and a dialyzer FX-220(Fresenius Medical Care GmbH, Bad Homburg, Germany) was used. For high-volume Pre O-HDF, it was established as 600 mL/min, and a hemodiafilter MFX-21Meco (Nipro Co., Osaka, Japan) was used under a displacing solution flow rate of 400 mL/min and displacing solution volume of 90 L. For Post O-HDF, it was established as 600 mL/min, and a hemodiafilter MFX-21Meco was used under a displacing solution flow rate of 44 mL/min and displacing solution volume of 10 L. According to the 2016 Annual Dialysis Data Report by the Japanese Society for Dialysis Therapy, the mean replacement fluid volume of Post O-HDF was 10.2L . We set the replacement fluid volume with reference to the average. Filtration is started at 15 min after the start of dialysis to prevent excessive leakage of albumin. In both procedures, the duration of treatment was 4 h, and the blood flow volume was 200 mL/min (Table 3).
These dialysis conditions were changed only once, and data were collected at that time. The patients’ original therapeutic mode and a sequential order of therapeutic modes in this study are different (Table 4).
We compared the leakages of total amino acid (TAA), non-essential amino acid (NEAA), and essential amino acid (EAA), clear spaces (CSs), β2-microglobulin (β2-MG) reduction rate, Kt/V urea, and albumin (Alb) leakage among the three procedures.
Twenty amino acids (aspartic acid, threonine, serine, asparagine, glutamic acid, glutamine, proline, glycine, alanine, valine, cystine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, tryptophan, lysine, and arginine) were measured by liquid chromatography–mass spectrometry.
Yamashita reported that loss of solutes with different pre-dialysis concentrations is better to be calculated as a ratio of the two and compared because the loss of solutes and pre-dialysis concentration are directly proportional . CS denotes the volume at which the concentration of the solute of interest becomes zero. Clear space was calculated using the following equation:
Here, cpre is the pre-dialysis concentration of amino acids and m is the leakage of amino acids.
Spent dialysate was also sampled continuously from the drain line at a flow rate of 2 L/h using a pump. Levels of 20 amino acids (aspartic acid, threonine, serine, asparagine, glutamic acid, glutamine, proline, glycine, alanine, valine, cystine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, tryptophan, lysine, arginine) were measured using liquid chromatography–mass spectrometry. Amino acids were categorized into TAAs, NEAAs (aspartic acid, serine, asparagine, glutamic acid, glutamine, proline, glycine, alanine, cystine, tyrosine, arginine), and EAAs (threonine, valine, methionine, isoleucine, leucine, phenylalanine, histidine, tryptophan, lysine).
Results are expressed as means ± SD. ANOVA were used for statistical analysis, and a p value of less than 0.05 was considered significant. All statistical analyses were carried out using StatView version 5.0
The study protocol was approved by the Institutional Ethical Committee of Kurata Hospital (Approval No. 2019–5).
TAA leakages after high-volume Pre O-HDF, HD, and Post O-HDF were 4,511 ± 797 mg, 6,309 ± 1,072 mg, and 6,792 ± 876 mg, respectively. NEAA leakages were 2,892 ± 632 mg, 4,008 ± 772 mg, and 4,274 ± 679 mg, respectively. EAA leakages were 1,619 ± 286 mg, 2,301 ± 414 mg, and 2,517 ± 302 mg, respectively. The values after high-volume Pre O-HDF were significantly lower than Post O-HDF (p < 0.01 each). The values of TAA and EAA, after high-volume Pre O-HDF were significantly lower than HD (p < 0.01) (Fig. 1).
The CSs of TAA after high-volume Pre O-HDF, HD, and Post O-HDF were 14.6 ± 2.2 L, 17.7 ± 3.0 L, and 19.3 ± 2.1 L, respectively. Those of NEAA were 14.0 ± 2.2 L, 17.4 ± 3.0 L, and 18.5 ± 2.0 L, respectively. Those of EAA were 15.7 ± 2.2 L, 18.4 ± 3.1 L, and 21.1 ± 2.9 L, respectively. The values after high-volume Pre O-HDF were significantly lower than HD (TAA and NEAA: p < 0.05) and Post O-HDF (p < 0.01 each) (Fig. 2).
Table 5 shows the results of the β2-MG reduction rates and Kt/V for urea among the three procedures. The β2-MG reduction rates after high-volume Pre O-HDF were significantly lower than Post O-HDF (p < 0.05).
The Kt/V for urea were not significantly different.
Albumin leakages were below the detection limit (< 1 g) in the three procedures.
Johansen et al. studied a cohort of 2275 adults who participated in the Dialysis Morbidity and Mortality Wave 2 study, of whom two-thirds met their definition of frailty. They revealed that frailty was independently associated with higher risk of death and with the combined outcome of death or hospitalization. Frailty is extremely common and is associated with adverse outcomes among incident dialysis patients. They concluded that given its prevalence and consequences, increased research efforts should focus on interventions aimed to prevent or attenuate frailty in the dialysis population .
In elderly patients, the muscle protein synthetic response to protein ingestion is reduced . Furthermore, amino acids leak during dialytic therapy; therefore, to replenish a lack of the pooled plasma amino, decomposition of the skeletal muscle may progress . Considering these, treatment conditions for reducing amino acid leakage are required to prevent flail sarcopenia, which has recently been emphasized, especially in elderly patients receiving dialysis.
According to the “Age and sex of HDF/HD patients 2017” published by the Japanese Society for Dialysis Therapy in 2017, the rate of HDF patients is higher than that of HD patients regardless of sex among those aged < 74 years, whereas the rate of HD patients is higher than that of HDF patients among those aged ≥ 75 years .
We previously reported that AA losses are lower during Pre O-HDF than HD of the same Kt/V for urea . However, in clinical practice, Kt/V for urea of Pre O-HDF and HD or Post O-HDF is rarely the same. In most cases, Pre O-HDF will be lower than HD or Post O-HDF. For that reason, in this study, we examined three treatment modes under conditions that could be prescribed in actual clinical practice.
The reason for prescribing pre-HDF of 90L was that a higher replacement flow rate would reduce the flow rate of dialysate into the dialysis membrane and reduce the efficiency of removal of small molecular weight substances by diffusion, which would inhibit amino acid leakage. This is suggested by the fact that the Kt/V of Urea, which has almost the same molecular weight as amino acids, was significantly lower than that of other dialysis conditions. In this study, high-volume Pre O-HDF with a hemodiafilter, through which Alb leakage is slight, reduced AA leakage in comparison with HD and Post O-HDF, and also reduced CS in comparison with Post O-HDF. The Kt/V value was not significantly among the three procedures. However, a Kt/V value of 1.2 to be secured at minimum, which is recommended in the guidelines for maintenance hemodialysis: hemodialysis prescriptions established by the Japanese Society for Dialysis Therapy, could be maintained . Amino acid leakage showed no significant difference between HD and Post O-HDF. Therefore, high-volume Pre O-HDF is the most advantageous blood purification method for elderly dialysis patients or those with malnutrition from the viewpoint of dietetics. It may also be useful for the prevention of sarcopenia and frail.
Our study has a limitation. It is because each of the three treatment modes was performed only once, so it is not clear whether these treatment modes contribute to the improvement in patients' nutritional status in the long term.
Under the treatment conditions we performed this time, high-volume Pre O-HDF reduces amino acid leakage in comparison with HD and Post O-HDF. High-volume Pre O-HDF is a therapeutic mode that suppresses amino acid leakage. The features of this method developed in Japan may be elicited through such a usage.
Availability of data and materials
The datasets analyzed during this study are available from the corresponding author on reasonable request.
- Pre O-HDF:
Pre-dilution on-line hemodiafiltration
- Post O-HDF:
Post-dilution on-line hemodiafiltration
Total amino acid
Non-essential amino acid
Essential amino acid
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The study protocol was approved by the Institutional Ethical Committee of Kurata Hospital (Approval No. 2019–5). All participants were provided with the opportunity to decline to participate in the study.
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Kato, M., Urabe, S., Matsuzawa, S. et al. High-volume pre-dilution on-line hemodiafiltration is the adequate blood purification method from the viewpoint of amino acid nutrition. Ren Replace Ther 8, 51 (2022). https://doi.org/10.1186/s41100-022-00441-4