Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Metabolomic Approach
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | MAU (n = 34) | Mau (n = 14) | Control (n = 8) | p Value |
---|---|---|---|---|
Gender | ||||
Male | 20 (58.8) | 6 (42.9) | 4 (50.0) | 0.597 |
Female | 14 (41.2) | 8 (57.1) | 4 (50.0) | |
Age (years) | 61.5 ± 8.5 | 68.1 ± 5.6 | 66.9 ± 4.6 | 0.013 * |
BMI (kg/m2) | 27.9 ± 4.8 | 26.4 ± 5.2 | 25.4 ± 3.4 | 0.341 |
HbA1c (%) | 7.73 ± 1.31 | 7.29 ± 0.74 | 7.34 ± 0.44 | 0.393 |
Duration of DM (years) | 13.9 ± 7.3 | 13.3 ± 5.7 | 14.8 ± 6.8 | 0.890 |
SBP (mmHg) | 134.7 ± 10.9 | 134.9 ± 8.35 | 137.1 ± 11.0 | 0.833 |
DBP (mmHg) | 78.0 ± 11.5 | 76.3 ± 6.12 | 77.8 ± 11.6 | 0.873 |
UACR (mg/g) ‡ | 1831.0 ± 1640.5 | 146.5 ± 85.9 | 10.6 ± 6.4 | <0.001 * |
Cr (mg/dL) ‡ | 1.92 ± 1.32 | 1.27 ± 0.26 | 1.33 ± 0.30 | 0.103 |
eGFR (mL/min/1.73 m2) ‡ | 42.9 ± 18.6 | 50.1 ± 12.8 | 49.2 ± 12.8 | 0.325 |
CKD stage II | 4 (11.8) | 4 (28.6) | 1 (12.5) | 0.314 |
CKD stage III | 22 (64.7) | 9 (64.3) | 7 (87.5) | |
CKD stage IV, V | 8 (23.5) | 1 (7.1) | 0 | |
OAD with | ||||
Metformin | 14 (41.2) | 7 (50.0) | 6 (75.0) | 0.260 |
Sulfonylurea | 24 (70.6) | 10 (71.4) | 6 (75.0) | 1.000 |
DPP4 inhibitor | 15 (44.1) | 9 (64.3) | 5 (62.5) | 0.412 |
GLP-1R agonist SGLT2 inhibitor | 4 (11.2) 5 (14.7) | 0 0 | 0 0 | 0.332 0.308 |
Insulin injection | 13 (38.2) | 3 (21.4) | 2 (25.0) | 0.603 |
Anti-hypertensive drugs | ||||
Beta-blacker | 8 (23.5) | 7 (50.0) | 2 (25.0) | 0.195 |
CCB | 22 (64.7) | 10 (71.4) | 4 (50.0) | 0.569 |
Diuretics | 4 (11.8) | 3 (21.4) | 0 | 0.376 |
Metabolites | MAU (n = 34) | Mau (n = 14) | Control (n = 8) | p Value |
---|---|---|---|---|
Amino acids | ||||
Ser | 99.9 ± 25.0 | 119.9 ± 31.8 | 126.0 ± 24.8 | 0.016 * |
Trp | 44.5 ± 9.32 | 51.3 ± 7.62 | 52.3 ± 15.7 | 0.042 * |
Tyr | 53.3 ± 10.8 | 66.1 ± 7.57 | 64.6 ± 16.7 | 0.001 * |
Orn ‡ | 122.7 ± 35.3 | 158.1 ± 68.2 | 95.9 ± 31.8 | 0.020 * |
Phe ‡ | 65.7 ± 13.6 | 75.1 ± 10.3 | 66.9 ± 13.2 | 0.007 * |
Biogenic amines | ||||
Kyn | 3.10 ± 0.89 | 3.14 ± 0.56 | 2.56 ± 0.72 | 0.207 |
Kyn/Trp | 0.073 ± 0.028 | 0.062 ± 0.014 | 0.050 ± 0.013 | 0.046 * |
Glycerophospholipids | ||||
PC ae C44:3 ‡ | 0.102 ± 0.022 | 0.118 ± 0.028 | 0.126 ± 0.025 | 0.025 * |
lysoPC a C24:0 | 0.138 ± 0.032 | 0.164 ± 0.031 | 0.166 ± 0.034 | 0.013 * |
lysoPC a C26:1 ‡ | 0.027 ± 0.009 | 0.034 ± 0.008 | 0.034 ± 0.008 | 0.006 * |
Sphingolipids | ||||
SM C26:0 | 0.208 ± 0.047 | 0.242 ± 0.062 | 0.249 ± 0.041 | 0.036 * |
Metabolites | MAU Group | Metabolites | Mau Group | ||||
---|---|---|---|---|---|---|---|
Responder (n = 20) | Non-Responder (n = 14) | p Value | Responder (n = 7) | Non-Responder (n = 7) | p Value | ||
Amino acids | Amino acids | ||||||
Ser | 95.7 ± 25.7 | 105.1 ± 24.1 | 0.306 | Ser | 129.3 ± 41.3 | 110.4 ± 16.5 | 0.296 |
Trp | 42.4 ± 6.84 | 47.6 ± 11.6 | 0.108 | Trp ‡ | 52.2 ± 4.75 | 50.3 ± 10.1 | 0.749 |
Tyr | 53.7 ± 10.3 | 52.8 ± 11.9 | 0.805 | Tyr | 66.1 ± 5.10 | 66.1 ± 9.91 | 1.000 |
Orn ‡ | 126.3 ± 29.7 | 118.3 ± 41.9 | 0.351 | Orn | 165.6 ± 57.2 | 150.6 ± 81.6 | 0.698 |
Phe ‡ | 68.4 ± 15.6 | 61.8 ± 9.10 | 0.178 | Phe ‡ | 78.3 ± 11.6 | 71.9 ± 8.51 | 0.142 |
Biogenic amines | Biogenic amines | ||||||
Kyn ‡ | 3.32 ± 0.97 | 2.79 ± 0.67 | 0.112 | Kyn | 2.93 ± 0.59 | 3.34 ± 0.48 | 0.175 |
Kyn/Trp ‡ | 0.081 ± 0.031 | 0.060 ± 0.015 | 0.025 * | Kyn/Trp ‡ | 0.056 ± 0.008 | 0.069 ± 0.017 | 0.085 |
Glycerophospholipids | Glycerophospholipids | ||||||
PC ae C44:3 ‡ | 0.103 ± 0.025 | 0.100 ± 0.018 | 0.834 | PC ae C44:3 | 0.116 ± 0.036 | 0.121 ± 0.020 | 0.746 |
lysoPC a C24:0 | 0.135 ± 0.028 | 0.141 ± 0.037 | 0.608 | lysoPC a C24:0 | 0.153 ± 0.029 | 0.175 ± 0.030 | 0.187 |
lysoPC a C26:1 ‡ | 0.027 ± 0.010 | 0.026 ± 0.006 | 0.888 | lysoPC a C26:1 | 0.032 ± 0.009 | 0.036 ± 0.007 | 0.297 |
Sphingolipids | Sphingolipids | ||||||
SM C26:0 | 0.209 ± 0.054 | 0.208 ± 0.038 | 0.969 | SM C26:0 | 0.254 ± 0.079 | 0.231 ± 0.040 | 0.494 |
Models | Multivariate Odds Ratio (95% Confidence Interval) | p Value |
---|---|---|
Unadjusted model | 0.639 (0.415-0.983) | 0.041 * |
Model 1 (age) | 0.644 (0.417-0.994) | 0.047 * |
Model 2 (SBP) | 0.619 (0.386-0.991) | 0.046 * |
Model 3 (eGFR) | 0.377 (0.148-0.964) | 0.042 * |
Model 4 (gender) | 0.319 (0.112-0.907) | 0.032 * |
Model 5 (HbA1c) | 0.326 (0.112-0.951) | 0.040 * |
Model 6 (duration of diabetes) | 0.218 (0.057-0.834) | 0.026 * |
Model 7 (use of DPP4 inhibitor or GLP-1R agonist or SGLT-2 inhibitor) | 0.098 (0.012-0.814) | 0.032 * |
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Wu, M.-H.; Lin, C.-N.; Chiu, D.T.-Y.; Chen, S.-T. Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease. Diagnostics 2020, 10, 207. https://doi.org/10.3390/diagnostics10040207
Wu M-H, Lin C-N, Chiu DT-Y, Chen S-T. Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease. Diagnostics. 2020; 10(4):207. https://doi.org/10.3390/diagnostics10040207
Chicago/Turabian StyleWu, Ming-Hsien, Chia-Ni Lin, Daniel Tsun-Yee Chiu, and Szu-Tah Chen. 2020. "Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease" Diagnostics 10, no. 4: 207. https://doi.org/10.3390/diagnostics10040207