Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design and Study Population
2.2. Hemodialysis Settings
2.3. Sample Collection and Laboratory Measurements
2.4. Comparison of Daily Losses between Hemodialysis Patients and Controls
2.5. Intradialytic Changes in Amino Acid Concentrations in Hemodialysis Patients
2.6. Single Dialysis Losses, Dialytic Clearance, and Fractional Clearance in Hemodialysis Patients
2.7. Assessment of Severe Fatigue
2.8. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Comparison of Amino Acid Concentrations between Hemodialysis Patients and Controls
3.3. Daily Amino Acid Losses in Hemodialysis Patients and Controls
3.4. Determinants of Total Amino Acid Losses in Hemodialysis Patients
3.5. Intradialytic Changes in Plasma Concentrations in Hemodialysis Patients
3.6. Single Hemodialysis Amino Acid Losses, Dialytic Amino Acid Clearances, and Relative Contribution of Dialysis and Urine to Daily Losses
3.7. Associations of Plasma Amino Acid Concentrations with Severe Fatigue
3.8. Associations of Daily Amino Acids Losses and Protein Intake with Severe Fatigue
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Hemodialysis Patients (n = 59) | Controls (n = 33) | p-Value | |
---|---|---|---|
Demographics | |||
Age, years | 65 ± 15 | 54 ± 10 | <0.001 |
Sex, n male (%) | 37 (63) | 15 (45) | 0.2 |
Dialysis-related | |||
Dialysis vintage, months | 15 (6; 39) | – | – |
Dialysis sessions, n (%) | |||
Two sessions per week | 3 (5) | – | – |
Three sessions per week | 56 (95) | – | – |
Dialysate volume, L | 135 ± 27 | – | – |
Ultrafiltration volume, L | 1.9 ± 0.9 | – | – |
Kt/V | 1.4 ± 0.3 | – | – |
Residual diuresis, n (%) | 32 (54) | 33 (100) | <0.001 |
Urinary volume 1, L | 0.9 ± 0.6 | 2.5 ± 0.9 | <0.001 |
Urinary protein excretion, g/24 h | 0.7 (0.3; 1.3) | ||
Plasma albumin, g/L | 39 ± 5 | 45 ± 2 | <0.001 |
Hemoglobin, mmol/L | 6.9 ± 0.7 | 8.8 ± 0.8 | <0.001 |
Body composition | |||
Weight predialysis 2, kg | 80 ± 16 | 77 ± 17 | 0.3 |
Weight postdialysis, kg | 78 ± 16 | – | – |
Height, m | 1.75 ± 0.09 | 1.72 ± 0.10 | 0.2 |
BMI 3, kg/m2 | 25.5 ± 4.3 | 25.6 ± 4.3 | 0.4 |
Protein intake | |||
Protein intake absolute, g/24 h | 64 ± 21 | 84 ± 21 | <0.001 |
Protein intake per kg bodyweight, g/kg/24 h | 0.82 ± 0.23 | 1.11 ± 0.21 | <0.001 |
Metabolite | Predialysis Concentration in Hemodialysis Patients (μmol/L) | Concentration in Healthy Controls (μmol/L) | Proportional Difference * | p-Value |
---|---|---|---|---|
Essential | ||||
Histidine | 69 ± 19 | 74 ± 12 | –7% | 0.2 |
Isoleucine | 63 ± 23 | 61 ± 18 | +3% | 0.6 |
Leucine | 103 ± 41 | 110 ± 29 | –6% | 0.4 |
Lysine | 141 ± 36 | 171 ± 37 | –18% | <0.001 |
Methionine | 19 ± 7 | 21 ± 5 | –10% | 0.03 |
Phenylalanine | 68 ± 22 | 57 ± 9 | +19% | 0.002 |
Threonine | 87 ± 29 | 115 ± 24 | –24% | <0.001 |
Tryptophan | 22 (20; 28) | 54 (46; 57) | –59% | <0.001 |
Valine | 186 ± 59 | 213 ± 51 | –13% | 0.03 |
Non-essential | ||||
Alanine | 351 ± 135 | 423 ± 113 | –17% | 0.01 |
Arginine | 77 ± 22 | 78 ± 17 | –1% | 0.7 |
Asparagine | 53 ± 16 | 61 ± 11 | –13% | 0.004 |
Citrulline | 78 (61; 95) | 28 (24; 32) | +179% | <0.001 |
Glutamic acid | 101 (69; 161) | 57 (45; 81) | +78% | <0.001 |
Glutamine | 514 ± 111 | 575 ± 87 | –11% | 0.008 |
Glycine | 260 ± 84 | 202 ± 54 | +29% | <0.001 |
Ornithine | 63 ± 20 | 59 ± 16 | +7% | 0.4 |
Proline | 276 (223; 322) | 248 (197; 321) | +11% | 0.3 |
Serine | 61 ± 19 | 103 ± 19 | –41% | <0.001 |
Taurine | 58 (41; 87) | 40 (37; 50) | +45% | 0.014 |
Tyrosine | 45 ± 16 | 62 ± 18 | –27% | <0.001 |
Total amino acids | ||||
Total BCAAs | 353 ± 119 | 384 ± 94 | –9% | 0.2 |
Total essential | 761 ± 200 | 875 ± 155 | –13% | 0.006 |
Total non-essential | 2052 ± 587 | 1977 ± 328 | +4% | 0.4 |
Total all amino acids | 2813 ± 693 | 2852 ± 427 | –1% | 0.7 |
Metabolite | Daily Losses in Hemodialysis Patients (μmol/24 h) | Daily Losses in Controls (μmol/24 h) | Ratio of Hemodialysis to Controls | p-Value |
---|---|---|---|---|
Essential | ||||
Histidine | 862 ± 270 | 698 ± 463 | 1.2 | 0.07 |
Isoleucine | 799 ± 338 | 12 ± 7 | 67 | <0.001 |
Leucine | 1382 ± 587 | 67 ± 23 | 21 | <0.001 |
Lysine | 1505 (1233; 1845) | 209 (157; 288) | 7 | <0.001 |
Methionine | 172 ± 95 | 5 ± 2 | 34 | <0.001 |
Phenylalanine | 729 (631; 967) | 68 (52; 103) | 11 | <0.001 |
Threonine | 1043 (731; 1279) | 105 (81; 161) | 10 | <0.001 |
Tryptophan | 216 ± 63 | 148 ± 57 | 1.5 | <0.001 |
Valine | 2017 (1606; 2614) | 42 (35; 54) | 45 | <0.001 |
Non-essential | ||||
Alanine | 3926 ± 1548 | 361 ± 219 | 11 | <0.001 |
Arginine | 826 ± 377 | 34 ± 15 | 24 | <0.001 |
Asparagine | 747 ± 290 | 122 ± 82 | 6 | <0.001 |
Citrulline | 463 (347; 570) | 11 (7; 13) | 42 | <0.001 |
Glutamic acid | 966 ± 559 | 35 ± 33 | 28 | <0.001 |
Glutamine | 6954 ± 2410 | 449 ± 211 | 15 | <0.001 |
Glycine | 3502 ± 1271 | 1521 ± 848 | 2 | <0.001 |
Ornithine | 541 ± 194 | 22 ± 17 | 25 | <0.001 |
Proline | 3601 ± 1351 | 8 ± 5 | 450 | <0.001 |
Serine | 754 (572; 1004) | 324 (236; 467) | 2 | <0.001 |
Taurine | 132 (24; 235) | 339 (204; 668) | 0.4 | <0.001 |
Tyrosine | 462 ± 192 | 105 ± 68 | 4 | <0.001 |
Totals | ||||
Total BCAAs | 4307 ± 1717 | 125 ± 52 | 34 | <0.001 |
Total essential | 9060 ± 3287 | 1463 ± 862 | 6 | <0.001 |
Total non-essential | 23,059 ± 7284 | 3837 ± 1939 | 6 | <0.001 |
Total losses | 32,119 ± 10,221 | 5300 ± 2749 | 6 | <0.001 |
Metabolite | Predialysis Concentration (μmol/L) | Postdialysis Concentration (μmol/L) | Absolute Change (μmol/L) | Proportional Difference | p-Value |
---|---|---|---|---|---|
Essential | |||||
Histidine | 69 ± 19 | 54 ± 14 | –15 ± 13 | –22% | <0.001 |
Isoleucine | 63 ± 23 | 74 ± 22 | +11 ± 26 | +17% | 0.002 |
Leucine | 103 ± 41 | 123 ± 38 | +20 ± 46 | +20% | 0.001 |
Lysine | 141 ± 36 | 133 ± 37 | –7 ± 38 | –5% | 0.14 |
Methionine | 19 ± 7 | 19 ± 6 | +1 ± 7 | +5% | 0.46 |
Phenylalanine | 68 ± 22 | 65 ± 13 | –3 ± 18 | –4% | 0.27 |
Threonine | 87 ± 29 | 80 ± 22 | –7 ± 22 | –8% | 0.02 |
Tryptophan | 22 (20; 28) | 27 (24; 34) | +5 (0; 15) | +23% | <0.001 |
Valine | 186 ± 59 | 146 ± 37 | –38 ± 52 | –20% | <0.001 |
Non-essential | |||||
Alanine | 351 ± 135 | 251 ± 85 | –99 ± 110 | –28% | <0.001 |
Arginine | 77 ± 22 | 60 ± 19 | –17 ± 23 | –22% | <0.001 |
Asparagine | 53 ± 16 | 50 ± 15 | –3 ± 14 | –6% | 0.10 |
Citrulline | 78 (61; 95) | 34 (27; 46) | –42 (27; 50) | –54% | <0.001 |
Glutamic acid | 101 (69; 161) | 108 (64; 138) | +2 (–26; 14) | +2% | 0.78 |
Glutamine | 514 ± 111 | 457 ± 96 | –58 ± 84 | –11% | <0.001 |
Glycine | 260 ± 84 | 203 ± 55 | –57 ± 57 | –22% | <0.001 |
Ornithine | 63 ± 20 | 51 ± 12 | –12 ± 17 | –19% | <0.001 |
Proline | 276 (223; 322) | 230 (212; 280) | –33 (– 83; 16) | –12% | 0.002 |
Serine | 61 ± 19 | 60 ± 18 | –1 ± 13 | –2% | 0.54 |
Taurine | 58 (41 − 87) | 35 (23; 53) | –17 (–4; –39) | –29% | <0.001 |
Tyrosine | 45 ± 16 | 45 ± 12 | –0 ± 16 | –0% | 0.97 |
Total amino acids | |||||
Total BCAAs | 353 ± 119 | 343 ± 94 | –7 ± 119 | –3% | 0.7 |
Total essential | 761 ± 200 | 724 ± 170 | –34 ± 206 | –5% | 0.2 |
Total non-essential | 2052 ± 587 | 1664 ± 309 | –384 ± 510 | –19% | <0.001 |
Total amino acids | 2813 ± 693 | 2388 ± 442 | –418 ± 637 | –15% | <0.001 |
Model 1 | Model 2 | |||
---|---|---|---|---|
Odds Ratio (95% Confidence Interval) | p-Value | Odds Ratio (95% Confidence Interval) | p-Value | |
Essential | ||||
Histidine | 1.21 (0.66; 2.38) | 0.5 | 1.97 (0.91; 4.97) | 0.1 |
Isoleucine | 0.83 (0.42; 1.53) | 0.6 | 0.88 (0.43; 1.71) | 0.7 |
Leucine | 0.75 (0.38; 1.37) | 0.4 | 0.77 (0.37; 1.50) | 0.5 |
Lysine | 0.80 (0.41; 1.46) | 0.5 | 0.78 (0.36; 1.51) | 0.5 |
Methionine | 0.80 (0.41; 1.47) | 0.5 | 0.98 (0.47; 2.01) | 0.9 |
Phenylalanine | 0.95 (0.46; 1.85) | 0.9 | 1.05 (0.48; 2.20) | 0.9 |
Threonine | 0.88 (0.48; 1.61) | 0.7 | 1.05 (0.53; 2.15) | 0.9 |
Tryptophan | 1.52 (0.81; 3.00) | 0.2 | 1.70 (0.87; 3.66) | 0.1 |
Valine | 0.77 (0.41; 1.41) | 0.4 | 0.79 (0.39; 1.53) | 0.5 |
Non-essential | ||||
Alanine | 1.42 (0.80; 2.61) | 0.2 | 1.44 (0.80; 2.73) | 0.2 |
Arginine | 0.63 (0.30; 1.21) | 0.2 | 0.66 (0.28; 1.36) | 0.3 |
Asparagine | 0.70 (0.35; 1.29) | 0.3 | 0.85 (0.38; 1.78) | 0.7 |
Citrulline | 0.92 (0.50; 1.66) | 0.8 | 1.14 (0.58; 2.30) | 0.7 |
Glutamic acid | 1.03 (0.50; 1.84) | 0.9 | 0.89 (0.40; 1.66) | 0.7 |
Glutamine | 0.99 (0.54; 1.80) | 0.9 | 1.36 (0.67; 2.84) | 0.4 |
Glycine | 0.76 (0.39; 1.39) | 0.4 | 0.92 (0.43; 1.87) | 0.8 |
Ornithine | 0.84 (0.44; 1.53) | 0.6 | 0.91 (0.46; 1.74) | 0.8 |
Proline | 2.55 (1.17; 7.12) | 0.042 | 2.97 (1.27; 9.26) | 0.032 |
Serine | 0.60 (0.30; 1.11) | 0.1 | 0.71 (0.33; 1.39) | 0.3 |
Taurine * | 0.41 (0.17; 0.84) | 0.027 | 0.30 (0.10; 0.70) | 0.014 |
Tyrosine | 0.98 (0.51; 1.86) | 0.9 | 1.18 (0.57; 2.50) | 0.7 |
Average amino acids | ||||
BCAAs | 0.77 (0.40; 1.41) | 0.4 | 0.80 (0.39; 1.54) | 0.5 |
Essential | 0.83 (0.44; 1.51) | 0.6 | 0.92 (0.47; 1.75) | 0.8 |
Non-essential | 1.05 (0.57; 1.89) | 0.5 | 1.15 (0.63; 2.16) | 0.6 |
Total amino acids | 0.99 (0.54; 1.78) | 0.9 | 1.10 (0.60; 2.08) | 0.7 |
Model 1 | Model 2 | |||
---|---|---|---|---|
Daily Amino Acid Losses | OR (95% CI) | p-Value | OR (95% CI) | p-Value |
Essential | ||||
Histidine | 0.93 (0.47; 1.81) | 0.8 | 0.95 (0.46; 1.88) | 0.9 |
Isoleucine | 0.75 (0.38; 1.37) | 0.4 | 0.62 (0.28; 1.21) | 0.2 |
Leucine | 0.68 (0.34; 1.27) | 0.2 | 0.54 (0.24; 1.09) | 0.1 |
Lysine | 0.79 (0.40; 1.49) | 0.5 | 0.60 (0.26; 1.24) | 0.2 |
Methionine | 0.70 (0.35; 1.31) | 0.3 | 0.71 (0.34; 1.36) | 0.3 |
Phenylalanine | 0.90 (0.45; 1.64) | 0.7 | 0.80 (0.37; 1.51) | 0.5 |
Threonine | 0.88 (0.45; 1.68) | 0.7 | 0.82 (0.40; 1.64) | 0.6 |
Tryptophan * | 1.31 (0.40; 5.00) | 0.6 | 1.18 (0.35; 4.55) | 0.8 |
Valine | 0.74 (0.38; 1.38) | 0.4 | 0.60 (0.27; 1.19) | 0.2 |
Non-essential | ||||
Alanine | 1.26 (0.68; 2.37) | 0.5 | 1.20 (0.61; 2.38) | 0.6 |
Arginine | 0.86 (0.46; 1.62) | 0.6 | 0.82 (0.40; 1.64) | 0.6 |
Asparagine | 0.74 (0.36; 1.47) | 0.4 | 0.77 (0.34; 1.61) | 0.5 |
Citrulline | 0.84 (0.46; 1.50) | 0.6 | 0.81 (0.44; 1.46) | 0.5 |
Glutamic acid | 0.84 (0.44; 1.53) | 0.6 | 0.41 (0.15; 0.97) | 0.06 |
Glutamine | 0.99 (0.52; 1.89) | 0.9 | 1.01 (0.51; 1.98) | 0.9 |
Glycine | 0.67 (0.33; 1.28) | 0.2 | 0.62 (0.27; 1.34) | 0.2 |
Ornithine | 0.79 (0.40; 1.50) | 0.5 | 0.71 (0.33; 1.40) | 0.3 |
Proline | 1.46 (0.78; 2.83) | 0.2 | 1.50 (0.77; 3.04) | 0.2 |
Serine | 0.89 (0.47; 1.63) | 0.7 | 0.97 (0.49; 1.85) | 0.9 |
Taurine * | 0.69 (0.47; 0.97) | 0.043 | 0.64 (0.42; 0.93) | 0.027 |
Tyrosine | 0.83 (0.44; 1.47) | 0.5 | 0.78 (0.42; 1.41) | 0.4 |
Average amino acids | ||||
BCAAs | 0.72 (0.36; 1.33) | 0.3 | 0.58 (0.26; 1.15) | 0.1 |
Essential | 0.77 (0.39; 1.44) | 0.4 | 0.65 (0.30; 1.28) | 0.2 |
Non-essential | 0.98 (0.51; 1.84) | 0.9 | 0.94 (0.47; 1.86) | 0.9 |
Total amino acids | 0.91 (0.47; 1.70) | 0.8 | 0.84 (0.42; 1.64) | 0.6 |
Dietary intake | ||||
Protein intake | 0.18 (0.04; 0.50) | 0.003 | 0.18 (0.04; 0.54) | 0.007 |
Protein intake per kg bodyweight | 0.22 (0.07; 0.53) | 0.003 | 0.23 (0.07; 0.57) | 0.006 |
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Post, A.; Kremer, D.; Groothof, D.; van der Veen, Y.; de Blaauw, P.; van der Krogt, J.; Kema, I.P.; Westerhuis, R.; Heiner-Fokkema, M.R.; Bakker, S.J.L.; et al. Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients. Nutrients 2022, 14, 2810. https://doi.org/10.3390/nu14142810
Post A, Kremer D, Groothof D, van der Veen Y, de Blaauw P, van der Krogt J, Kema IP, Westerhuis R, Heiner-Fokkema MR, Bakker SJL, et al. Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients. Nutrients. 2022; 14(14):2810. https://doi.org/10.3390/nu14142810
Chicago/Turabian StylePost, Adrian, Daan Kremer, Dion Groothof, Yvonne van der Veen, Pim de Blaauw, Jennifer van der Krogt, Ido P. Kema, Ralf Westerhuis, M. Rebecca Heiner-Fokkema, Stephan J. L. Bakker, and et al. 2022. "Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients" Nutrients 14, no. 14: 2810. https://doi.org/10.3390/nu14142810