INTRODUCTION
Hemodialysis (HD) and/or continuous ambulatory peritoneal dialysis (CAPD) may induce catabolism and increase protein requirements above the baseline of non-dialyzed uremic patients
1, 2). Besides, there is a considerable amount of amino acid and/or protein loss during replacement therapy, and the amount of amino acid loss varies depending on the type of dialysis. The average loss of free amino acids in the dialysis fluid has been reported to be 5–8 g/dialysis during HD, and 1.2–3.4 g/24 hr during CAPD
3–5). Substantial loss of protein in the dialysate, which accelerates the decline of plasma amino acid concentrations, is a major drawback for CAPD which is not present for HD.
CAPD treatment, with its basic differences from HD in terms of small and large molecule dialysis profiles, continuous 24-hour-a-day blood purification and cardiovascular and blood chemistry stability may be the preferred replacement therapy for ESRD
6). Since the introduction of CAPD, nephrologists have been questioning the ability of the method to achieve the same results as HD. But, clinical and ethical considerations, including the right of patients to select their preferred dialysis treatment, make such an evaluation impossible in prospective, unbiased studies.
Most early comparative studies failed to show significant differences in overall patient survival between CAPD and HD
7–12). However, all of these studies were retrospective and limited by the lack of quality case-mix adjustment. Recently, a report appeared suggesting that patients treated by PD had a relatively increased risk of death compared with patients undergoing HD
13). The United States Renal Data System
14) also reported that CAPD patients had a 19% higher mortality rate compared to those receiving HD. The cause of this discrepancy in mortality rates is poorly understood.
The concentration of plasma amino acids reflects disturbances in whole-body protein and amino acid metabolism, even though plasma amino acids constitute only a small portion of the body’s free amino acid pool
15). Differences in the structure of amino acids, and amino acid body requirements for amino acids, suggest that individual amino acids may have organ-specific metabolic and pharmacological functions
16). Protein malnutrition is an important risk factor in ESRD. Also, plasma amino acid concentrations for which the physiological function differs from that of protein, may be an independent risk factor in ESRD. Much recent data support the concept that specific nutrients have the capacity to affect clinical outcome
17), independent of their general nutritional effects
18). In this regard, further research is necessary to understand the optimal balance required for each amino acid to support immune, gut and anabolic functions which may influence the mortality rate in patients with ESRD.
There is no doubt about the existence of low amino acid levels in both HD and CAPD patients. However, the difference in plasma amino acid levels between these two groups has not been quantified. The purpose of this study is to compare the plasma amino acid concentrations between patients with ESRD on HD and CAPD matched by age, sex and body mass index.
RESULTS
Amino acid concentrations: Among 20 amino acids, 17 amino acids were measured, including 10 EAA (valine, leucine, isoleucine, threonine, methionine, lysine, phenylalanine, tryptophan, histidine, arginine) and 7 NEAA (serine, glycine, alanine, proline, tyrosine, aspartate, glutamate).
A. Plasma amino acid concentrations in the control group and HD group (
Fig. 1). The concentrations of aspartate (8±4 vs. 75±61
μ mole/L) and proline (234±81 vs. 168±63
μ mole/L) were higher in the HD group than in the control group. Serine (67±26 vs. 87±42
μ mole/L), tyrosine (36±19 vs. 52±21
μ mole/L), valine (164±74 vs. 233±107
μ mole/L), isoleucine (59±30 vs. 79±39
μ mole/L) and leucine (93±48 vs. 137±68
μ mole/L) were lower in the HD group than in the control group. BCAA (447±210 vs. 315±146
μ mole/L) and EAA (1046±421 vs. 898±369
μ mole/L) were lower in the ESRD group but there was no difference between NEAA (1003±371 vs. 1120±445
μ mole/L) and TAA (2060±778 vs. 2070±808
μ mole/L) for the control and HD group.
B. Comparison of plasma amino acid levels between the CAPD and HD group (
Fig. 1): All of the amino acid concentrations were higher in the patients on HD than on CAPD as follows: aspartate (75±61 vs.36.5±20.1
μ mole/L), glutamate (62.5±44.8 vs.22.0±13.2
μ mole/L), serine (66.6±26.2 vs. 28.8±9.2
μ mole/L), glycine (277.0±132.9 vs. 121.4±41.3
μ mole/L), histidine (68.7±36.2 vs. 23.0±8.5
μ mole/L), arginine (76.0±36.5 vs. 43.4±19.6
μ mole/L), threonine (93.0±45.3 vs. 32.1±12.6
μ mole/L), alanine(368.6±169.7 vs. 203.3±102.2
μ mole/L), proline (234.0±81.4 vs. 84.6±31.6
μ mole/L), tyrosine (36.1±19.0 vs. 18.3±8.9
μ mole/L), valine (163.6±74.4 vs. 76.1±34.6
μ mole/L), methionine (21.7±11.9 vs. 10.0±3.7
μ mole/L), isoleucine (58.7±29.6 vs, 26.4±12.9
μ mole/L), leucine (93.2±47.7 vs. 42.7±18.5
μ mole/L), phenylalanine (63.9±26.5 vs. 24.3±11.4
μ mole/L), tryptophan (138.4±82.2 vs. 57.1±19.7
μ mole/L), lysine (119.9±53.6 vs. 53.4±20.3
μ mole/L (p ä 0.001). All of the TAA (2017.3±781.1 vs. 903.3±316.1
μ mole/L), EAA (1201.8±492.6 vs. 567.6±223.2
μ mole/L), NEAA (815.5±308.6 vs. 335.7±100.2
μ mole/L) and BCAA (315.0±146.0 vs. 145.2±65.0
μ mole/L) concentrations were lower in the patients on CAPD than on HD.
C. Comparison of protein concentrations in hemodialysate and peritoneal dialysate: The loss of protein in peritoneal dialysis solution was 2.0±0.2 g/L of peritoneal dialysate but no loss was detected in hemodialysates.
D. Comparison of plasma and dialysate amino acid concentrations in patients on CAPD (
Fig. 2): The concentrations of aspartate (36.5±20.1 vs. 97.8±22,6
μ mole/L), glycine (121.4±41.3 vs. 172.2±43.8
μ mole/L), arginine (43.4±19.6 vs. 123.8±35.5
μ mole/L), proline (84.6±31.6 vs. 193.8±44.2
μ mole/L) methionine (10.0±3.7 vs. 26.3±7.9
μ mole/L), phenylalanine (24.3±11.4 vs. 53.0±15.1
μ mole/L), and lysine (53.4±20.3 vs. 93.4±16.2
μ mole/L), were higher in the dialysate than in the plasma (p ä 0.001).
The concentrations of glutamate (22.0±13.2 vs. 17.5±10.4 μ mole/L), serine (28.8±9.2 vs. 30.3±10.4 μ mole/L), histidine (23.0±8.5 vs. 20.3±6,3 μ mole/L), threonine (32.1±12.6 vs. 42,9±16.7 μ mole/L), alanine (203.3±102.2 vs. 262.0±46.0 μ mole/L), tyrosine (l8.3±8,9 vs. 22.0±4.0 μ mole/L), valine (76.1±34.6 vs. 86.8±31.3 μ mole/L), isoleucine (26.4±12.9 vs. 31.4±4.9 μ mole/L), and leucine (42.7±18.5 vs. 44,4±5.0 μ mole/L) showed no difference between the dialysate and the plasma.
The concentration of tryptophan was higher in the plasma (57.1±19.7 μ mole/L) than in the dialysate (26.0±3.5 mmole/L) (p ä 0.001).
The levels of TAA (903.3±316.1 vs. 1343.9±144.1 μ mole/L), EAA (567.6±223.2 vs. 757.3±60,0 μ mole/L), and NEAA (335.7±100.2 vs. 586.6±98.4 μ mole/L) were higher in the plasma than in the dialysate (p=0.0001). The levels of BCAA in the plasma (145.2±65.0 μ mole/L), showed no significant difference compared to that in the dialysate (162.6±27.7 μ mole/L).
The amino acid concentrations in the dialysate and those in the plasma were of three types. In type 1: most amino acid concentrations in the plasma and dialysate were very similar (
Fig. 4). In type 2: most amino acid concentrations were higher in the dialysate than in the plasma (
Fig. 3). In type 3: Some amino acid concentrations were higher in the dialysate than in the plasma (
Fig. 5).
E. Amino acid concentrations in HD dialysate: Amino acid concentrations in the HD dialysate were as follows: aspartate; 0.8±0.4 μ mole/L, glutamate; 27.1±9.2 μ mole/L, serine; 9.3±3.0 μ mole/L), glycine; 32.5±3.9 μ mole/L, histidine; 5.3±1.3 μ mole/L, arginine; 12.5±4.3 μ mole/L, threonine 11.1±4.0 μ mole/L, alanine; 33.3 ±6.9 μ mole/L, proline ; 37.8±10.1 μ mole/L, tyrosine; 4.4±1.4 μ mole/L, valine; 25.2±4.3 μ mole/L, methionine; 3.2±0.5 μ mole/L, isoleucine; 10.7±1.7 μ mole/L, leucine; 14.6±3.6 μ mole/L, phenylalanine; 8.4±1.1 μ mole/L, tryptophan; 9.5±2.8 μ mole/L, lysine; 11.5±3.1 μ mole/L, TAA; 257.3±49.1 μ mole/L, EAA; 112.0±22.4 μ mole/L, NEAA; 145.3±27.7 μ mole/L.
F. Amino acid loss during dialysis (
Fig. 3): Of the CAPD group, TAA loss over a one week period (1.81±0.62 mmole per each 2 L bag and 38.0 f 13.0 mmole for one week) was significantly lower than that of the HD group (61.8±13.0 – 92.7±19.7 mmole over one week, depending on the amount of dialysis) (pä0.0l).
DISCUSSION
In our study, plasma amino acid concentrations were lower in the CAPD group than in the HD group. In agreement with previous reports
3–5), amino acid losses were considerable during dialysis. But amino acid loss during a given time was two to three times greater in the HD group than in the CAPD group. Therefore, lowered amino acid concentrations observed in the CAPD group could not be explained by amino acid loss during dialysis.
The mechanism which induces plasma amino acid abnormalities in ESRD is not linked to a single cause but encompasses a multitude of factors. Many patients experience anorexia, nausea, vomiting caused by intercurrent illness, inadequate dialysis or medication, and a moderate amount of amino acids are lost during each hemodialysis
3–5). In addition, altered lipid metabolism
19) metabolic acidosis
20, 21), decreased muscle mass
22), and insulin resistance
23, 24) may also be closely related to the mechanism inducing plasma amino acid abnormalities in ESRD.
It is not known whether lipid metabolism, metabolic acidosis and insulin resistance differ between patients on CAPD and HD. In order to minimize the effect of diet on the plasma amino acid concentrations, we instructed the patients to have for supper, the evening before the study day, at least half a bowl of rice as the main dish and about 50g of meat and/or fish with some vegetables. Also, there was no difference in the levels of serum cholesterol and albumin. Therefore, a difference in the diet content does not seem to be a contributing factor to the discrepancy in amino acid concentrations between the CAPD and HD groups.
Kt/V urea was 0.9–1.2 in the HD group, retrospectively. However, we could not match the adequacy of dialysis between the CAPD and HD groups because the dialysis adequacy criteria were not measured for the CAPD group.
There was no difference in the anthropometric measurements between the CAPD and HD groups, suggesting that any difference in the muscle mass does not influence the discrepancy of amino acid concentrations between the two groups.
The BCAA levels were lower in the HD group than in the control group. But there was no difference in the concentrations of the TAA, EAA and NEAA between the control and HD groups. It is known that BCAA are decarboxylated by the same enzymes, and available evidence indicates that the decrease cannot be accounted for by excessive uptake by splanchnic tissue in ESRD
25). Compared to the control group, the concentrations of serine, tyrosine valine, isoleucine, leucine and lysine were lower in the HD group, but the concentrations of aspartate, arginine and proline were higher. The concentrations of glutamate, glycine, histidine, threonine, alanine, methionine, phenylalanine and tryptophan were similar in the control and HD groups. In contrast to a previous report
26), which showed lowered threonine and higher glycine concentrations in the HD group, no difference in the concentrations between the control and HD group were found. It was both unexpected and interesting to find that all of the plasma amino acid concentrations were significantly lower in the CAPD patients than in the HD patients in our study.
The fact that the amino acid loss during dialysis was greater in the HD group than in the CAPD group, together with the observation of protein loss only in the peritoneal dialysate, indicates that the lowered amino acid concentrations in the patients on PD seem mainly due to protein loss through the peritoneal dialysate.
Investigation of the mechanisms for amino acid loss during peritoneal dialysis could not be performed through this study. But we were able to find that the concentrations of all the plasma amino acids were similar to those in the peritoneal dialysate while, in other cases, some or all of the amino acid concentrations were higher in the peritoneal dialysate than in the plasma. These findings suggest that the mechanism for amino acid loss through peritoneal dialysis differs from case to case.
In conclusion, our results suggest that amino acid concentrations are lower in patients with ESRD on CAPD than on HD. This seems to be due to protein loss through the peritoneal dialysate. We believe that lowered amino acid concentration, frequently observed in the ESRD patients on CAPD, may worsen the clinical outcome for CAPD patients compared to HD patients. Our speculation may be reinforced by the new concept of the so called “amino acid-based peritoneal dialysis solutions” recently described by other authors
27–30)