Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Cohort
2.2. Blood Sampling
2.3. The Exploratory Metabolome Profiling Analysis
2.4. The Amino Acids Profiling Analysis
2.5. Measurement of 5-HT, and 5-HIAA
2.6. Measurement of Serum Creatinine and Vancomycin Concentration
2.7. Statistical Analysis
3. Results
3.1. Subject Characteristics
3.2. The Results of the Exploratory Metabolome Profiling Analysis
3.3. The Results of the Amino Acids Profiling Analysis
3.4. The Results of Measurement of 5-HT and 5-HIAA
3.5. The AUC-ROC Analysis of 5-HT 5-HIAA, and 5-HIAA/5-HT for VAKI
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical Characteristics | Overall | VAKI | Non-VAKI | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Total Non-VAKI | p-Value a | Infection | p-Value a | CKD | p-Value a | HC | p-Value a | |||
Number of Subjects | 97 | 28 | 69 | 23 | 23 | 23 | ||||
Age, yr (mean ± SD) | 60.2 ± 13.1 | 60.4 ± 14.5 | 60.2 ± 13.1 | N.S | 58.4 ± 12.2 | N.S | 63.4 ± 12.1 | N.S | 58.4 ± 13.1 | N.S |
range | 20–85 | 20–85 | 21–82 | 37–82 | 21–72 | 24–81 | ||||
Female (%) | 38 (39%) | 10 (36%) | 28 (41%) | N.S | 9 (39%) | N.S | 9 (39%) | N.S | 10 (43%) | N.S |
BMI (kg/m2) | 23.4 ± 3.4 | 21.8 ± 3.2 | 24.0 ± 3.2 | 0.002 | 23.2 ± 3.5 | N.S | 24.3 ± 3.4 | 0.018 | 24.6 ± 2.7 | 0.02 |
SCr (mg/dL) | 1.16 ± 0.60 | 1.60 ± 0.96 | 1.05 ± 0.51 | <0.001 | 0.62 ± 0.21 | <0.001 | 1.61 ± 0.29 | N.S | 0.85 ± 0.15 | <0.001 |
GFR (mL/min/1.73 m2) | 67.8 ± 31.4 | 45.9 ± 12.8 | 76.8 ± 32.4 | <0.001 | 107.8 ± 23.9 | <0.001 | 39.5 ± 4.3 | N.S | 84.6 ± 11.8 | <0.001 |
CRP (mg/dL) | 0.26 ± 6.78 | 5.78 ± 8.74 | 2.39 ± 4.88 | <0.001 | 7.19 ± 6.31 | N.S | 0.07 ± 0.94 | <0.001 | 0.04 ± 0.71 | <0.001 |
Vancomycin Cmin | 27.3 ± 5.3 | 14.2 ± 2.6 | <0.001 | |||||||
(μg/mL) |
Parameters | VAKI | Non-VAKI | |||||||
---|---|---|---|---|---|---|---|---|---|
(μmol/mL) | Total Non-VAKI | p-Value a | Infection | p-Value a | CKD | p-Value a | HC | p-Value a | |
Alanine | 417.3 (324.0–487.3) | 296.0 (207.5–393.3) | 0.002 | 290.6 (241.5–529.9) | N.S | 201.2 (141.7–267.2) | <0.001 | 371.7 (339.4–420.3) | N.S |
Beta-alanine | 2.1 (1.4–2.9) | 4.7 (2.4–7.2) | <0.001 | 7.3 (6.2–8.6) | <0.001 | 3.5 (2.4–6.5) | 0.01 | 2.4 (1.9–4.7) | N.S |
Anserine | 0.0 (0.0–0.0) | 0.0 (0.0–0.7) | <0.001 | 0.5 (0.0–0.8) | <0.001 | 0.0 (0.0–0.0) | N.S | 0.6 (0.0–0.9) | <0.001 |
Aminoadipic acid | 0.0 (0.0–1.0) | 0.6 (0.0–1.1) | N.S | 0.6 (0.0–1.0) | N.S | 0.7 (0.0–1.1) | N.S | 0.5 (0.0.–0.9) | N.S |
Alpha-aminobutyric acid | 10.2 (8.2–13.4) | 13.5 (8.5–17.9) | 0.05 | 14.9 (11.4–19.1) | 0.002 | 6.4 (3.9–11.5) | 0.037 | 16.6 (11.7–20.0) | <0.001 |
Gamma-aminobutyric acid | 0.0 (0.0–0.2) | 1.4 (0.9–2.0) | <0.001 | 1.9 (1.3–2.5) | <0.001 | 0.9 (0.5–1.9) | <0.001 | 1.3 (1.1–1.6) | <0.001 |
Beta-aminoisobutyric acid | 2.8 (1.4–4.8) | 0.7 (0.0–2.3) | 0.002 | 0.5 (0.0–1.7) | 0.001 | 2.6 (0.0–9.8) | N.S | 0.7 (0.0–1.1) | <0.001 |
Arginine | 72.8 (59.2–84.2) | 61.9 (37.3–95.0) | N.S | 62.0 (40.6–143.2) | N.S | 37.3 (23.2–59.1) | <0.001 | 73.7 (59.4–117.9) | N.S |
Asparagine | 29.5 (23.7–34.9) | 28.2 (19.4–36.3) | N.S | 30.1 (20.4–43.0) | N.S | 19.4 (13.0–33.5) | 0.011 | 30.5 (23.2–36.5) | N.S |
Aspartic acid | 11.3 (8.5–16.4) | 19.6 (11.3–36.0) | 0.01 | 24.2 (19.0–41.6) | <0.001 | 11.8 (9.1–37.3) | N.S | 15.3 (10.4–32.6) | N.S |
Carnosine | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | 0.024 | 0.0 (0.0–0.3) | 0.017 | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | 0.039 |
Citrulline | 35.0 (29.3–39.4) | 20.9 (13.2–30.5) | <0.001 | 17.6 (11.2–39.5) | 0.002 | 14.1 (9.8–22.0) | <0.001 | 27.4 (22.4–33.0) | 0.007 |
Cystathionine | 0.0 (0.0–0.0) | 0.0 (0.0–0.8) | N.S | 0.0 (0.0–0.0) | N.S | 0.8 (0.0–1.6) | 0.002 | 0.6 (0.0–0.5) | N.S |
Cystine | 3.7 (1.9–8.1) | 5.6 (2.0–13.0) | N.S | 11.4 (7.8–13.5) | <0.001 | 10.4 (5.2–29.4) | <0.001 | 1.2 (0.0–2.0) | <0.001 |
Ethanolamine | 5.8 (4.8–6.6) | 9.1 (5.5–11.9) | 0.037 | 8.9 (7.0–11.6) | 0.01 | 5.5 (3.4–10.3) | N.S | 10.9 (6.7–15.4) | 0.003 |
Glutamic acid | 54.1 (39.8–76.9) | 82.2 (54.1–114.5) | 0.016 | 100.4 (72.5–158.6) | 0.002 | 58.9 (35.6–113.1) | N.S | 72.0 (56.4–99.6) | 0.034 |
Glutamine | 313 | 257.5 | N.S | 232.6 | 0.022 | 140.5 | <0.001 | 382.3 | 0.028 |
(275.1–370.9) | (145.1–378.5) | (170.5–326.9) | (97.4–244.7) | (298.5–570.1) | |||||
Glycine | 136 | 142.7 | N.S | 149.7 | N.S | 110.3 | 0.043 | 165.9 | N.S |
(117.2–198.9) | (119.8–266.4) | (125.4–267.9) | (98.4–244.7) | (133.3–288.5) | |||||
Histidine | 34.9 (32.1–38.6) | 40.2 (29.4–57.7) | N.S | 37.1 (28.2–54.3) | N.S | 35.7 (17.3–46.6) | N.S | 47.0 (37.7–80.2) | 0.001 |
Homocysteine | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S |
Dehydroxylysine | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S |
Hydroxyproline | 7.6 (5.4–10.4) | 6.1 (3.9–9.4) | N.S | 6.6 (3.9–9.4) | N.S | 6.1 (3.1–14.9) | N.S | 5.2 (4.4–8.8) | N.S |
Isoleucine) | 32.0 (25.8–39.0) | 35.2 (25.5–51.5) | N.S | 41.0 (31.1–59.0) | 0.041 | 24.4 (16.4–40.7) | N.S | 37.9 (29.2–53.1) | N.S |
Leucine | 80.2 (59.3–99.1) | 93.8 (72.1–137.3) | N.S | 103.1 (87.4–140.8) | 0.015 | 53.1 (34.5–105.9) | N.S | 106.7 (81.6–147.4) | 0.006 |
Lysine | 99.2 (83.1–114.8) | 122.2 (78.2–157.5) | N.S | 122.2 (83.7–170.2) | N.S | 73.1 (46.0–127.1) | N.S | 131.1 | 0.001 |
(105.5–185.6) | |||||||||
Methionine | 6.0 (5.1–8.9) | 16.1 (7.2–29.7) | 0.002 | 9.3 (5.9–15.9) | N.S | 8.0 (4.6–15.9) | N.S | 34.7 (26.9–40.0) | <0.001 |
1-methylhistidine | 7.4 (5.9–9.9) | 9.2 (6.2–12.6) | N.S | 13.6 (10.1–14.9) | <0.001 | 6.3 (4.1–10.1) | N.S | 8.8 (6.2–10.3) | N.S |
3-methylhistidine | 4.8 (4.0–7.2) | 3.4 (1.6–6.8) | 0.024 | 1.7 (0.9–10.7) | 0.018 | 5.7 (4.2–12.3) | N.S | 2.1 (1.6–4.3) | <0.001 |
Ornithine | 48.9 (38.5–77.1) | 53.7 (40.9–92.6) | N.S | 88.4 (51.3–117.3) | 0.039 | 51.9 (35.7–90.3) | N.S | 49.8 (42.5–69.9) | N.S |
Phenylalanine | 51.5 (46.2–67.7) | 64.6 (47.0–87.6) | N.S | 76.4 (55.5–100.3) | 0.003 | 65.4 (40.9–104.7) | N.S | 54.9 (37.2–82.4) | N.S |
O-phosphoethanolamine | 0.0 (0.0–0.0) | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.0) | N.S |
O-phosphoserine | 1.6 (1.2–2.0) | 3.0 (1.7–4.6) | <0.001 | 3.8 (1.9–.5.1) | 0.002 | 2.4 (1.8–3.5) | 0.009 | 3.4 (1.6–8.3) | 0.002 |
Proline | 97.7 (76.9–127.9) | 83.3 (49.3–129.9) | N.S | 89.5 (86.7–141.9) | N.S | 53.2 (44.4–106.1) | 0.013 | 74.9 (57.1–169.0) | N.S |
Sarcosine | 0.0 (0.0–0.6) | 0.6 (0.0–0.8) | N.S | 0.6 (0.0–1.2) | N.S | 0.0 (0.0–0.8) | N.S | 0.6 (0.0–0.8) | N.S |
Serine | 78.2 (69.2–93.9) | 88.0 (70.1–138.7) | N.S | 100.3 (86.7–141.9) | 0.01 | 63.3 (40.8–82.7) | 0.021 | 111.0 (75.1–1843.4) | 0.009 |
Taurine | 40.6 (32.6–50.4) | 65.2 (34.7–99.3) | 0.02 | 69.8 (39.9–109.3) | N.S | 34.7 (29.1–73.9) | N.S | 81.0 (60.8–127.1) | <0.001 |
Threonine | 66.2 (52.9–80.8) | 59.0 (40.7–89.4) | N.S | 64.6 (46.0–114.2) | N.S | 38.1 (30.4–63.9) | 0.001 | 59.8 (50.3–118.3) | N.S |
Tryptophan | 21.0 (17.6–24.6) | 25.0 (13.0–36.9) | N.S | 18.9 (12.2–37.0) | N.S | 14.3 (10.8–27.2) | N.S | 35.4 (25.0–47.8) | <0.001 |
Tyrosine | 34.1 (26.7–37.2) | 39.1 (26.9–57.9) | N.S | 36.4 (25.2–37.0) | N.S | 37.2 (18.4–54.4) | N.S | 41.7 (25.0–48.6) | 0.011 |
Valine | 129.3 | 142.1 | N.S | 178.1 | 0.034 | 91.9 (51.4–140.8) | 0.009 | 156.9 | 0.014 |
(114.9–160.5) | (101.3–220.3) | (138.0–222.2) | (125.5–256.8) | ||||||
Argininosuccinic acid | 0.0 (0.0–0.0) | 0.0 (0.0–1.1) | <0.001 | 0.6 (0.0–1.3) | <0.001 | 0.0 (0.0–0.6) | 0.002 | 0.0 (0.0–2.0) | <0.001 |
Homocitrulline | 1.1 (0.7–1.5) | 0.0 (0.0–0.7) | <0.001 | 0.0 (0.0–0.4) | <0.001 | 0.0 (0.0–0.8) | 0.001 | 0.0 (0.0–0.7) | <0.001 |
All-isoleucine | 0.0 (0.0–0.0) | 0.0 (0.0–0.8) | 0.003 | 0.0 (0.0–0.0) | N.S | 0.0 (0.0–0.9) | 0.007 | 0.8 (0.0–1.4) | <0.001 |
Parameters | VAKI | Non-VAKI | |||||||
---|---|---|---|---|---|---|---|---|---|
Total Non-VAKI | p-Value a | Infection | p-Value a | CKD | p-Value a | HC | p-Value a | ||
Trp (μmol/mL) | 21.0 (17.6–24.6) | 25.0 (13.0–36.9) | N.S | 18.9 (12.2–37.0) | N.S | 14.3 (10.8–27.2) | N.S | 35.4 (25.0–47.8) | 0.004 |
5-HT (ng/mL) | 47.8 (16.6–135.5) | 251.2 (114.5–389.3) | <0.001 | 87.5 (50.6–250.2) | N.S | 337.6 (195.8–520.0) | <0.001 | 345.2 (218.4–386.4) | <0.001 |
5-HIAA (ng/mL) | 249.4 (113.0–442.2) | 84.5(36.3–154.5) | <0.001 | 80.8 (35.2–258.7) | 0.006 | 85.7 (70.4–111.8) | 0.003 | 38.5 (27.7–171.2) | <0.001 |
5-HT/Trp | 2.0 (0.7–6.5) | 9.8(3.8–18.0) | <0.001 | 4.3 (1.6–16.2) | N.S | 20.0 (8.6–56.9) | <0.001 | 9.4 (4.8–12.1) | 0.017 |
5-HIAA/5-HT | 6.3 (1.9–14.0) | 0.4 ( 0.2–0.9) | <0.001 | 0.9 (0.5–1.9) | 0.032 | 0.2 (0.2–0.5) | <0.001 | 0.3 (0.1–0.7) | <0.001 |
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Lee, H.-S.; Kim, S.-M.; Jang, J.-H.; Park, H.-D.; Lee, S.-Y. Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury. Antioxidants 2021, 10, 895. https://doi.org/10.3390/antiox10060895
Lee H-S, Kim S-M, Jang J-H, Park H-D, Lee S-Y. Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury. Antioxidants. 2021; 10(6):895. https://doi.org/10.3390/antiox10060895
Chicago/Turabian StyleLee, Hyun-Seung, Sang-Mi Kim, Ja-Hyun Jang, Hyung-Doo Park, and Soo-Youn Lee. 2021. "Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury" Antioxidants 10, no. 6: 895. https://doi.org/10.3390/antiox10060895