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American Journal of Clinical Nutrition, Vol. 71, No. 3, 765-773, March 2000
© 2000 American Society for Clinical Nutrition

Original Research Communications

Amino acid losses during hemodialysis with polyacrylonitrile membranes: effect of intradialytic amino acid supplementation on plasma amino acid concentrations and nutritional variables in nondiabetic patients1,2,3

Juan F Navarro, Carmen Mora, Candelaria León, Rafael Martín-del Río, Manuel L Macía, Eduardo Gallego, Jesús Chahin, María L Méndez, Antonio Rivero and Javier García

1 From the Departments of Nephrology and Biochemistry and the Research Unit, Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Tenerife, Spain, and the Research Unit, Hospital Ramón y Cajal, Madrid.

2 Supported by grant 96/0370 from Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Madrid.

3 Address reprint requests to JF Navarro, Department of Nephrology, Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Tenerife, Spain.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Malnutrition is highly prevalent in hemodialysis patients. Amino acid (AA) losses during the dialysis procedure may be a contributing factor.

Objectives: The objectives of this study were 1) to prospectively evaluate AA losses and their effect on plasma AA concentrations during dialysis with polyacrylonitrile at baseline and after administration of AAs by intradialysis and 2) to investigate the effects of intradialytic AA supplementation on nutritional status.

Design: Seventeen stable patients without diabetes who were receiving hemodialysis were studied. In the first phase, AA losses were evaluated over 2 wk in 10 patients randomly assigned to receive AA supplementation. AA losses were analyzed during the first week without supplementation and during the second week with AA administration. In the second phase, the patients' nutritional status was investigated after 3 mo of AA supplementation and was compared with those in 7 patients not receiving AAs.

Results: Mean ( ± SD) AA losses during a 4-h dialysis session were 12 ± 2 g; there was a significant decrease in plasma AA concentrations (386 ± 298 µmol/L for essential and 902 ± 735 µmol/L for nonessential AAs). After administration of AAs, the losses increased to 28 ± 4 g. However, this procedure produced a positive net balance of AAs (10.6 ± 5.6 g for total AAs), preventing a reduction in plasma concentrations. After 3 mo of AA administration, there was a significant increase in protein catabolic rate and serum albumin and transferrin. This improvement occurred without any change in the dialysis dose, ruling out the possibility that an increase in dialysis efficiency played a role.

Conclusions: Intradialysis adequately provides AA supplements, prevents reductions in plasma AA concentrations, and favorably affects the nutritional status of patients receiving hemodialysis.

Key Words: Albumin • amino acid losses • amino acid supplementation • malnutrition • nutritional status • end-stage renal disease • hemodialysis • men and women • Spain


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Malnutrition is the most important nutritional problem in dialysis patients, showing up most often as a progressive loss of somatic and visceral protein stores (1–3). Patients receiving maintenance hemodialysis frequently have this complication, with up to 70% of these patients showing evidence of protein malnutrition (4). It has been shown that malnutrition is of great concern. A suboptimal nutritional status may impair rehabilitation and quality of life (1, 2, 5). Furthermore, dialysis patients with malnutrition have higher morbidity and mortality than do adequately nourished dialysis patients (5–7). Albumin is the most common serum protein and a standard for nutritional assessment. In various hemodialysis studies, low serum albumin was found in 13–70% of subjects (1, 8–11). Importantly, serum albumin concentration is a major predictor of survival in hemodialysis patients, there being a strong association between low serum albumin and mortality (11).

The pathogenesis of malnutrition in dialysis is multifactorial (12–14). In addition to low nutrient intake, hormonal and metabolic derangements, and superimposed illness, dialysis-related factors [specifically, loss of nutrients, including amino acids (AAs)] may have a substantial effect on malnutrition (15, 16). It was estimated that AA losses during the dialysis procedure represent between 3% and 12% of the patient's daily protein intake (17–19), and hemodialysis membranes can have a great influence on these losses. Most previous studies analyzing AA losses during hemodialysis used conventional cellulosic membranes. Those studies showed that the amount of AAs lost into the dialysate during one dialysis session can range from 4 to 13 g (17, 19–24). However, very few studies have investigated AA losses with the new synthetic dialysis membranes. Ikizler et al (19) found that mean losses of AAs during a 4-h hemodialysis session were 6 g with polymethylmethacrylate and 8 g with polysulfone. In a recent study, we found that, during a 3-h hemodialysis session, mean AA losses with polyacrylonitrile were 6 g, almost twice the losses observed with polysulfone (25).

The use of parenteral nutrient supplementation during the dialysis procedure may have benefits in hemodialysis patients (26). An improvement in nutritional variables and a reduction in mortality were reported after transient (27, 28) and long-term (29) use of intradialysis parenteral nutrition. However, data on the effect of intradialytic AA administration are scare. In prior studies, AAs were administered near the end of or immediately after the hemodialysis session (30, 31) and in all cases were infused in a glucose solution (22, 30, 31).

Therefore, we designed this study to analyze hourly and total AA losses when polyacrylonitrile membranes were used and to evaluate the effects of intradialytic AA administration without glucose on plasma AA concentrations and AA losses in the dialysate. We also prospectively compared the nutritional status of patients receiving intradialytic AAs with that of patients not receiving such supplementation.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Seventeen patients (9 men and 8 women) receiving regular long-term hemodialysis for >=12 mo participated in the study, which was conducted at the Hospital Nuestra Señora de Candelaria, Tenerife, Spain. Informed consent was obtained from all patients. The study was conducted according to the ethical guidelines of the Council for International Organizations of Medical Sciences. The mean (±SD) age of the patients was 50 ± 13 y and the mean duration of hemodialysis was 23 ± 9 mo. All patients were in stable clinical condition and free of medical complications. The causes of end-stage renal disease were hypertension (n = 8), glomerulonephritis (n = 7), and interstitial nephritis (n = 2). None of the patients had diabetes. Before entering the study, all patients had been receiving dialysis with polysulfone membranes. Residual renal function was negligible in all cases. All patients had been given a stable dose of recombinant human erythropoietin subcutaneously during the 3 mo before the study began and all were taking oral iron supplements (105 mg elemental Fe/d as ferrous sulfate). No patients had received 1,25-dihydroxycholecalciferol, glucocorticoids, androgens, or protein supplements. Predialysis serum bicarbonate concentrations were within the normal range in all patients (23 ± 3 mmol/L).

All patients were switched to dialysis with a polyacrylonitrile dialyzer (surface area: 1.7 m2; pore size: 15–45 m). Membranes were not reused. All patients received dialysis for 4 h/session; the blood flow rate was 300 mL/min and the dialysate flow rate was 500 mL/min. The dialysate composition was identical for all treatments: sodium, 140 mmol/L; potassium, 2 mmol/L; calcium, 3 mmol/L; bicarbonate, 39 mmol/L; chloride, 108 mmol/L; and glucose, 1 g/L. With use of a random-number table, the patients were selected and randomly assigned to receive (study group) or not receive (control group) intradialytic AA supplementation. At baseline, there were no significant differences between the 2 groups in demographic, nutritional, or dialytic variables (Table 1Go).


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  		TABLE 1. Baseline characteristics of study patients1
 
Experimental design
Phase 1: analysis of amino acid losses and plasma amino acid concentrations
AA losses and changes in plasma concentrations were investigated in the 10 patients randomly assigned to the supplementation group. Baseline AA losses were evaluated during the first week of this phase; during this time, each patient participated in 3 dialysis sessions, for a total of 30 sessions. During the dialysis sessions, patients received an intravenous infusion of 500 mL 0.9% NaCl (control). All patients fasted from midnight before the study until the end of the hemodialysis session in the morning of the next day. After this initial analysis, the protocol was repeated during the second week under the same conditions to assess the effect of AA supplementation on AA losses and plasma concentrations. Patients received an infusion of 500 mL containing 25.7 g free AAs with a ratio of essential to nonessential AAs of 0.39 (Aminoplasmal; Braun Medical, Barcelona, Spain). The AA composition of the infusate is shown in Table 2Go. Each solution was infused at a constant rate of 125 mL/h. There were no significant differences in the hourly ultrafiltration volume during the hemodialysis sessions. Mean weight loss was similar with the 2 infusions: 2.7 ± 0.3 kg with AA and 2.5 ± 0.4 kg with 0.9% NaCl. Likewise, there was no significant difference in the total dialysate volume collected after the dialysis sessions: 132 ± 8 L with AA and 129 ± 4 L with 0.9% NaCl.


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  		TABLE 2. Composition of the infused amino acid solution
 
Samples for measurement of plasma AA concentrations were obtained from the arterial blood line at the beginning and at the end of each dialysis session. Blood was collected in heparin-containing tubes and centrifuged at 2200 x g for 10 min at 20°C within 3 min of collection. Plasma was separated and deproteinized by adding sulfosalicylic acid. The supernate was then stored at -70°C until analyzed. Spent dialysate fluid was collected hourly into a tank during the dialysis session. Every hour, 20-mL samples of dialysate were obtained and stored at -70°C for measurement of AAs.

The amount of AAs lost into the dialysate (in mg) was calculated as dialysate AA concentration (in g/L) x dialysate volume (in mL). The net balance of AAs during hemodialysis with supplementation was calculated as follows:

Blood chemistries were assessed by using standard laboratory techniques. AAs were measured by reversed-phase HPLC (limit of detection: 1 mg/L) with an amino acid analyzer (model 6300; Beckman Instruments, Palo Alto, CA).

Phase 2: evaluation of nutritional status
After the analysis of AA losses and AA plasma concentrations during phase 1 of the study, the effect of AA supplementation on the nutritional status of hemodialysis patients was investigated. Subjects assigned to the supplementation group received 500 mL of an AA solution containing 25.7 g free AAs (Aminoplasmal; Braun Medical) during the dialysis sessions for 3 mo. Anthropometric and biochemical variables were compared with those of the 7 patients in the control group receiving dialysis without AA supplementation.

Anthropometric variables were measured by using standard techniques (32, 33) and included weight, body mass index (in kg/m2), triceps skinfold thickness, midarm circumference, and midarm muscle circumference. Triceps skinfold thickness and the midarm circumference were measured by using a Harpenden caliper (British Indicators, St Albans, United Kingdom) in the nonaccess arm at the midpoint between the acromion and olecranon. The midarm muscle circumference was derived from midarm circumference and triceps skinfold thickness (34). Biochemical variables included serum albumin and transferrin. Albumin was measured by immunonephelometry (normal range, 34–50 g/L).

For each patient, urea kinetic modeling was performed monthly to determine the dialysis dose and the protein catabolic rate. Blood urea nitrogen was measured before and after the midweek dialysis session and before the subsequent dialysis session. Postdialysis blood samples were drawn 30 min after disconnection from the dialysis equipment to avoid access and cardiopulmonary recirculation and regional blood flow–compartment effects (35, 36). The volume of distribution of urea was obtained according to the equations proposed by Watson et al (37). The urea generation rate was calculated from the increase in blood urea nitrogen during the interdialytic period and the volume of urea distribution. Normalized protein catabolic rate was obtained from the urea generation rate according to Sargent's formula (38, 39).

Statistical analysis
The statistical analysis was performed by using STATISTICS for WINDOWS (release 5.0, 1994; StatSoft, Tulsa, OK). AA plasma concentrations and AA losses into dialysate were expressed as means ± SDs. Comparisons of variables between the 2 groups (with and without supplementation) and the changes in plasma AA concentrations within groups were made by using Student's t test. The differences in hourly AA losses were analyzed by one-way repeated-measures analysis of variance and post hoc analysis by using Scheffe's procedure. Correlations between AA losses, plasma concentrations, and the net balance during the dialysis sessions were assessed by linear regression analysis. Because of the small number of patients, the nutritional variables were expressed as medians and ranges. Comparisons were made with the Mann-Whitney U test or the Wilcoxon matched-pairs test when appropriate. Significance was defined as P < 0.05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
In a comparison between procedures with and without AA supplementation there were no significant differences in baseline and postdialysis serum concentrations of creatinine, urea, sodium, potassium, chloride, bicarbonate, calcium, or phosphate. Predialysis plasma AA concentrations were also similar among procedures.

Hemodialysis without amino acid supplementation
Hourly AA losses during the dialysis session are shown in Table 3Go. Hourly losses were not significantly different among AAs during the dialysis procedure except for histidine and leucine, for which the amount lost was significantly higher during the third and fourth hours than during the first and second hours. The mean losses of essential, nonessential, branched-chain, and total AAs were 3700 ± 800, 8600 ± 1800, 1500 ± 400, and 12400 ± 2700 mg, respectively. Losses of essential AAs represented 30.9% of total losses. The most abundant essential AAs in the dialysate were valine and lysine; the most abundant nonessential AAs were glutamine and proline. Total AAs lost in the dialysate and losses of essential, nonessential, and branched-chain AAs were strongly correlated with predialysis plasma AA concentrations (r = 0.84, 0.83, 0.79, and 0.85, respectively; P < 0.01).


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  		TABLE 3. Hourly losses of individual amino acids during hemodialysis without amino acid supplementation1
 
Plasma AA concentrations before and after dialysis are shown in Table 4Go. At the end of the hemodialysis session, average plasma concentrations of essential, nonessential, branched-chain, and total AAs were significantly lower than baseline values: 680 ± 111 compared with 1066 ± 273 µmol/L (P < 0.01), 1797 ± 177 compared with 2313 ± 377 µmol/L (P < 0.05), 328 ± 58 compared with 537 ± 202 µmol/L (P < 0.05), and 2477 ± 265 compared with 3380 ± 638 µmol/L (P < 0.05), respectively. Plasma concentrations of all individual AAs were lower after dialysis; this decrease was significant for all AAs except arginine, glutamic acid, glutamine, phenylalanine, and proline. The greatest decreases in essential AAs were observed for valine and methionine; the greatest decreases in nonessential AAs were observed for aspartic acid and taurine.


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  		TABLE 4. Plasma amino acid concentrations before and after dialysis and percentage changes with and without supplementation1
 
Hemodialysis with amino acid supplementation
Total losses of individual AAs and AA groups during hemodialysis with and without supplementation are shown in Table 5Go. The amount of essential, nonessential, branched-chain, and total AAs lost during the dialysis procedure was significantly higher with than without AA supplementation. Likewise, the losses of individual AAs were significantly higher with supplementation, except for taurine, glutamine, and citrulline; the losses of these AAs, not contained in the infusate solution, were similar with and without supplementation. There was a direct correlation between plasma concentrations of essential, nonessential, branched-chain, and total AAs and the losses of these AAs in the dialysate (r = 0.95, 0.99, 0.92, and 0.97, respectively; P < 0.01).


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  		TABLE 5. Losses of amino acids per dialysis session with and without supplementation1
 
Mean plasma AA concentrations before and after dialysis with AA supplementation are shown in Table 4Go. Contrary to the result observed for dialysis without supplementation, only the plasma concentrations of asparagine, citrulline, cystine, and taurine decreased significantly. Moreover, the concentrations of many AAs tended to increase compared with predialysis values, although this increase was significant only for leucine. When we analyzed the individual groups of AAs, plasma concentrations of essential, nonessential, branched-chain, and total AAs were not significantly different after dialysis. The reductions in plasma nonessential and total AAs tended to be lower than those observed during hemodialysis without supplementation, although there were no significant differences between the 2 groups. Nevertheless, the change in the plasma concentrations of essential and branched-chain AAs after dialysis with supplementation was positive, reflecting an increase in the plasma concentrations of these AAs, and was significantly different from dialysis without supplementation (Table 4Go).

The mean net balance of individual AAs during hemodialysis with supplementation is shown in Table 6Go. There was a positive net balance for all AAs except arginine, cystine, and tyrosine. Furthermore, there was a significant negative correlation (P < 0.01) between the losses of these groups of AAs and their net balance during dialysis: essential, r = -0.76; nonessential, r = -0.97; branched chain, r = -0.84; and total, r = -0.94. At the end of the study, serum urea nitrogen tended to increase from baseline in patients receiving AA supplementation (16.4 ± 1.7 compared with 14.6 ± 1.4 mmol/L; P = 0.052). Serum bicarbonate did not change significantly during the study (baseline: 24 ± 3 mmol/L; third month: 22 ± 2 mmol/L).


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  		TABLE 6. Net balance of individual amino acids during hemodialysis with supplementation1
 
Evolution of nutritional variables
There were no significant differences in baseline characteristics nor in the nutritional status of the 2 study groups (Table 1Go). At the end of the study, anthropometric variables had not changed significantly in either group. However, the median serum albumin concentration increased significantly compared with baseline in patients receiving AA supplementation: 42.2 g/L (range: 38–44 g/L) compared with 36.2 g/L (34.5–40.7 g/L) (P < 0.05), whereas there was no significant variation in control subjects: 38.2 g/L (36.7–4.2 g/L) compared with 37 g/L (34–42 g/L). Furthermore, serum transferrin increased in patients receiving AAs [2.01 g/L (1.58–2.44 g/L) compared with 1.78 g/L (1.45–1.89 g/L) (P < 0.05)], but not in control subjects [1.7 g/L (1.4–2 g/L) compared with 1.84 g/L (1.45–2.2 g/L)]. Body iron stores were also analyzed. After 3 mo, the median serum ferritin concentration did not change significantly in patients receiving AAs or in control subjects compared with baseline: 244 µg/L (176–355 µg/L) compared with 250 µg/L (119–345 µg/L), and 208 µg/L (118–362 µg/L) compared with 253 µg/L (177–403 µg/L), respectively. In contrast, the protein catabolic rate was significantly higher at the end of the study than at baseline in patients receiving AAs [1.18 g•kg-1•d-1 (1.03–1.29 g•kg-1•d-1) compared with 1.07 g•kg-1•d-1 (0.89–1.16 g•kg-1•d-1) (P < 0.05), but not in control subjects [1.1 g•kg-1•d-1 (0.94–1.30 g•kg-1•d-1) compared with 1.1 g•kg-1•d-1 (0.87–1.28 g•kg-1•d-1)]. This increase in protein catabolic rate in patients receiving supplementation was not accompanied by a concomitant increase in dialysis dose [baseline: 1.21 (1.06–1.37); third month: 1.18 (1.01–1.33)].


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
A major contribution to the improvement in dialysis must be attributed to modern membranes, such as polyacrylonitrile. The increase in dialytic efficiency; the addition of new removal mechanisms, such as adsorption; and the improvement of biocompatibility indicators are evident benefits. However, these new membranes have disadvantages. They have been shown to cause hypersensitivity and allergic reactions, to interact adversely with some medications, and to cause nutrient losses. In addition, maintaining the sterility of the membranes is a concern.

Our results show that hemodialysis with polyacrylonitrile induces a total loss of {approx}12 g AAs during a standard 4-h dialysis session, with no differences in hourly losses. In a previous study (25) we found that dialysis with polyacrylonitrile removed {approx}6 g AAs. This difference may be explained by the larger surface area of the membrane used (1.7 compared with 0.9 m2) and the longer dialysis sessions (4 compared with 3 h) in the current study. In that previous study we found higher AA losses with polyacrylonitrile than with other membranes, such as polysulfone and cuprophane (25). Furthermore, Ikizler et al (19) reported that the mean losses during a 4-h session with polysulfone and polymethylmethacrylate were only 8.0 ± 2.8 and 6.1 ± 1.5 g, respectively, despite a similar surface area and the use of a higher blood flow (400 mL/min) than was used in the present study. This may reflect the differences in the intrinsic properties of the different membranes, such as physiochemical characteristics, electric charge, polymer composition, interface free energy, surface hydrophobicity or hydrophylicity, thickness, protein accumulation, and capacity for capture of AAs.

In the present study, the plasma concentrations of all individual AAs decreased after hemodialysis without supplementation; this decrease was significant for all groups of AAs. These variations resulted in a percentage reduction in plasma essential, nonessential, branched-chain, and total AAs of 32%, 20%, 32%, and 24%, respectively. Hemodialysis with polyacrylonitrile produced a greater reduction in the plasma concentrations of all groups of AAs than those reported by Ikizler et al (19), who used other synthetic membranes. However, in agreement with previous findings by other authors (19, 22) and by us (25), the decrease in plasma AAs does not explain the total losses during the dialysis session, suggesting the appearance of new AAs (40). Early studies showed a negative nitrogen balance on dialysis days compared with nondialysis days (41) and a 30% increase in the urea generation rate during hemodialysis (42, 43), suggesting that the dialysis procedure itself is catabolic.

Experimental studies by Gutierrez et al (44–46) with sham-hemodialysis showed that the release of AAs from skeletal muscle was enhanced when bioincompatible rather than biocompatible membranes were used because of a higher catabolic effect. However, AA losses during dialysis with biocompatible membranes showed that these membranes could induce a net protein catabolism. Furthermore, the average decrease in extracellular AAs in the current study was {approx}2.5 g [calculated as body wt of patients (kg) x 0.25 extracellular volume (L/kg body wt) x molecular wt of AAs (µg/µmol) x decrease in the plasma AA concentration (µmol/L)]. Thus, there must be other sources of AA losses, such as a disruption in intracellular AA pools, a net breakdown of protein and peptides, or a combination of both (22, 47).

A significant increase in AA losses and plasma AA concentrations after AA supplementation during dialysis was documented previously (22). In such studies, conventional cellulosic membranes were used and AAs were infused with a substantial amount of glucose. However, no data were reported on the effects of intradialysis AA administration with the new synthetic membranes. In the current study, AAs were supplemented without glucose or other nutrients to avoid potential confounding factors. After dialysis with AA supplementation, AA losses (28.2 ± 4.3 g) were significantly higher (P < 0.001) than those observed after dialysis without supplementation (12.4 ± 2.7 g). Nevertheless, supplementation resulted in a positive net balance of AAs (10.6 ± 5.6 g/session). Subsequently, not only was there an important reduction in the decrement of plasma nonessential and total AAs, but the percentage change in the plasma concentration of essential and branched-chain AAs was positive (14 ± 49% and 27 ± 61%, respectively). Furthermore, AA supplementation prevented the reduction of plasma AAs, with no significant modifications in the plasma concentrations of essential, nonessential, branched-chain, and total AAs after the dialysis session. Similar results were reported by Chazot et al (48), who investigated the effects of adding AAs to hemodialysate. These authors found that when AAs were added in a similar amount to normal postabsorptive values, the plasma AA concentrations did not change significantly, whereas, when AAs were added in amounts {approx}3 times normal postabsorptive values, the AA balance was positive and plasma AA concentrations increased. The results of the present study show that AA administration by parenteral intradialysis can prevent the reduction of plasma AAs in a way similar to that seen when AAs are administered in the dialysate. Furthermore, the total amount of AAs necessary to achieve this effect was significantly lower in our study than in the study by Chazot et al (25.7 and 46.4 g, respectively). Thus, it can be hypothesized that a mild increase in the initial amount of AAs administered in our study might result in a significant rise in plasma AA concentrations.

It was shown previously that uremic malnutrition significantly increases morbidity and mortality (6, 10, 49–51). On that basis, different methods of supplementing dialysis patients with nutrients have been proposed, including intradialytic parenteral nutrition. An important aspect of our study was that, whereas in most previous studies intradialysis nutrition consisted of a combination of dextrose, lipids, AAs with peptides, and, in some cases, trace metals, multivitamins, and folic acid, the patients in our study received a solution of only AAs.

In the assessment of the nutritional status of patients with renal disease, anthropometric and biochemical variables play meaningful roles (52, 53). Our results suggest that intradialytic AA administration improves several nutritional indexes in hemodialysis patients. Anthropometric variables did not change significantly after 3 mo of AA supplementation. These data differ from those published by Cano et al (26), who found an increase in body weight and arm muscle circumference after 3 mo of perdialytic parenteral nutrition. However, recent studies on the effect of prolonged parenteral nutrition by intradialysis showed that no changes in nutritional variables, particularly anthropometric values, occurred until after >=6 mo of therapy (27, 29). It is possible that the duration of our study (3 mo) was too short and that a longer follow-up time is necessary to enable any significant modification in anthropometric indexes to be observed. However, the biochemical variables (albumin and transferrin) increased significantly after only 3 mo of AA supplementation, which is consistent with the findings of other authors (26, 29, 54).

The biochemical measurement most frequently used to assess nutritional status is the serum albumin concentration. Low serum albumin was reported in 13–70% of hemodialysis patients (1, 8–11). This value is considered one of the most sensitive and early markers of malnutrition and a major predictor of outcome (55, 56). Qureshi et al (57) found that hospitalization rate and technique failure increased with decreased albumin concentrations. Lowrie and Lew (10) reported that serum albumin concentration was the best predictor of patient survival in an analysis performed in a cohort of >=12000 hemodialysis patients. These authors found that the risk of death increased with decreasing albumin concentrations; thus, an only slightly decreased albumin concentration (between 35 and 39 g/L) was associated with a 2 times greater relative risk of death compared with patients with a serum albumin concentration >=40 g/L. In the current study, the median serum albumin concentration increased in patients receiving AA supplementation from 36.2 g/L (range: 34.5–40.7 g/L) to 42.2 g/L (38–44 g/L) (P < 0.05) but did not change in control subjects. This early and significant increase in serum albumin may be important because it might be associated with an improvement in the relative risk of death. Likewise, serum transferrin was higher in patients who received supplementation. This variable has also been considered for evaluating the nutritional status of dialysis patients (53); furthermore, a recent study by Kalantar-Zadeh et al (58) showed that transferrin concentrations were strongly and directly correlated with the patients' nutritional status.

The fact that control patients did not show increases in these nutritional indexes over the same period suggests that AA supplementation might play a significant role in this improvement. The increase in albumin and transferrin suggests that the direct intravenous infusion of AAs promotes an effective utilization of these nutrients for protein synthesis. On the other hand, whereas there was no change in the protein catabolic rate in control subjects, a significant increase in the protein catabolic rate was evident in patients receiving AAs. The median protein catabolic rate in these subjects at the end of the study was 1.18 g•kg-1•d-1, very close to the dietary protein intake recommended by most authors for hemodialysis patients (1.2 g•kg-1•d-1) (59–61). In stable hemodialysis patients, the protein catabolic rate was shown to be an accurate index of protein intake (62). Lindsay and Spanner (63) observed a spontaneous increase in the protein catabolic rate after an increase in the dialysis dose, showing a direct correlation between both variables. However, the increment in the protein catabolic rate in our study occurred without any modification in the dialysis dose, ruling out the possibility that variations in dialysis efficiency might have played a role on the improvement in protein catabolic rate and the serum concentrations of albumin and transferrin.

A potential contributing factor to the rise in protein catabolic rate may have been an increase in dietary intake. Anorexia is an important concern in dialysis patients (61, 64). A variety of factors have been proposed as contributing to anorexia, including low plasma concentrations of branched-chain AAs (65). The branched-chain AAs (valine, isoleucine, and leucine) play a central role in metabolism; they are precursors for the synthesis of proteins and fatty acids and are regulators of insulin release, protein turnover, and skeletal muscle energy metabolism (66–69). Many authors reported that parenteral nutrition enriched with branched-chain AAs stimulated appetite and oral food intake in healthy subjects (65) and hemodialysis patients (26). Of greater interest to us was the observation that AA supplementation via intradialysis produced a positive net balance of branched-chain AAs and prevented a reduction in their plasma concentrations. As a result, it is possible to speculate that an increase in dietary intake might contribute to an improvement in nutritional variables.

In conclusion, the present study showed that AA losses during a standard 4-h hemodialysis session with polyacrylonitrile were {approx}12 g and resulted in important reductions in plasma concentrations in all AA groups. However, the reduction in plasma AA concentrations does not explain the total losses of AAs into dialysate. These total losses suggest that, despite a higher biocompatibility, synthetic membranes can produce a net catabolic effect. Administration of AAs via intradialysis results in higher AA losses, but this procedure can produce a positive net AA balance and prevent a reduction in plasma AA concentrations. Most importantly, AA supplementation by intradialysis produced a short-term improvement in nutritional variables, specifically, a significant increase in protein catabolic rate, serum albumin, and transferrin.


   ACKNOWLEDGMENTS
 
We thank Pamela La Lande for providing language assistance.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Bergstrom J. Nutrition and mortality in hemodialysis. J Am Soc Nephrol 1995;6:1329–41.[Abstract]
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Received for publication February 5, 1999. Accepted for publication September 23, 1999.




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