Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics and Biochemical Parameters
2.2. Renal Excretion of TMAO and Precursors
2.3. Hemodialysis Removal
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Subjects
5.2. Anthropometric Data
5.3. Blood Sampling
5.4. Glomerular Filtration Rate Assessment
5.4.1. Measured GFR (mGFR)
5.4.2. Estimated GFR (eGFR)
5.5. Clearance and Fractional Excretion Calculations
5.6. Quantification of Methylamines
5.7. Other Biochemical Measurements
5.8. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Controls | CKD Patients | Hemodialysis | p-Value | ||
---|---|---|---|---|---|---|
Stage 1–2 | Stage 3a–3b | Stage 4–5 | ||||
Sex, male/female | 13/5 | 26/23 | 9/22 | 12/3 | 7/4 | 0.0054 |
Age, y | 41 [34–47] a | 46 [30–58] a | 64 [45–69] b,c | 50 [33–74] a,c | 62 [48–75] a,c | 0.0014 |
BMI, kg/m2 | 24.1 [22.7–25.7] | 24.2 [20.6–26.0] | 24.5 [21.6–27.2] | 25.3 [21.0–30.9] | 22.4 [21.1–27.5] | 0.6427 |
Systolic BP, mmHg | 127.6 ± 21.0 | 122.8 ± 17.3 | 134.2 ± 21.9 | 128.5 ± 22.3 | 115.5 ± 19.1 | 0.1538 |
Diastolic BP, mmHg | 82.8 ± 13.5 | 77.8 ± 13.6 | 79.2 ± 13.3 | 79.7 ± 17.6 | 59.0 ± 2.8 | 0.2261 |
Creatinine, µmol/L | 67.9 ± 14.6 a | 87.8 ± 18.0 a,b | 119.6 ± 36.6 b | 268.8 ± 113.2 c | 689.0 ± 149.8 d | <0.0001 |
mGFR, mL/min. 1.73 m2 | 100 [93–107] a | 74 [66–83] b | 48 [41–54] c | 20 [14–24] c | NA | <0.0001 |
Urea, mmol/L | 4.4 [3.6–6.2] a | 5.9 [5.0–7.9] a,b | 9.3 [7.0–11.7] b,c | 21.5 [11.1–30.1] c | 16.1 [13.0–24.2] c | <0.0001 |
UA/C, mg/mmol | 0.8 [0.5–1.2] a | 1.2 [0.6–3.5] a,b | 2.5 [0.6–49.7] b,c | 38.3 [1.0–61.9] c | NA | 0.0001 |
Uric acid, mmol/L | 252 [185–310] a | 275 [222–348] a | 317 [279–356] a,b | 555 [465–624] b | ND | 0.0008 |
Protein intake, g/kg/day | 1.03 ± 0.34 | 0.96 ± 0.35 | 0.86 ± 0.23 | 0.81 ± 0.14 | 1.26 ± 0.47 | 0.3814 |
Bicarbonates, mmol/L | 25.0 [24.0–27.0] a | 25.0 [23.8–27.0] a | 24.5 [23.3–26.0] a,b | 20.5 [18.0–32.8] a,b | 22.0 [20.0–24.0] b | 0.0122 |
Proteins, g/L | 74 [71–78] a | 74 [71–78] a | 72 [66–74] a,b | 72 [66–76] a,b | 66 [65–71] b | 0.0015 |
Triglycerides, mmol/L | 0.84 [0.66–1.11] a,c | 1.00 [0.77–1.40] a,b | 1.17 [1.00–1.54] b | 1.55 [0.81–1.95] b | 1.24 [1.04–1.53] b,c | 0.0021 |
Total cholesterol, mmol/L | 4.82 [3.80–5.81] a,b | 5.22 [4.39–5.81] a | 4.84 [3.85–5.58] a,b | 3.99 [3.57–4.50] b | 3.26 [2.79–4.00] b | 0.0004 |
HDL-cholesterol, mmol/L | 1.03 [0.85–1.47] | 1.16 [1.02–1.43] | 1.11 [0.98–1.29] | 0.95 [0.82–1.27] | 1.14 [0.94–1.21] | 0.1569 |
LDL-cholesterol, mmol/L | 3.42 [2.36–4.06] a | 3.45 [2.73–3.97] a | 3.00 [2.10–3.49] a,b | 2.45 [1.71–2.81] b | 1.82 [1.22–2.16] b | <0.0001 |
Lipid Lowering treatments, % | 0.0 | 2.4 | 30.0 | 40.0 | 81.8 | <0.0001 |
Variable | rs | 95% CI | |
---|---|---|---|
Age, y | 0.30 | 0.12 to 0.47 | ** |
BMI, kg/m2 | 0.17 | −0.02 to 0.35 | ns |
UA/C, mg/mmol | 0.24 | 0.06 to 0.42 | ** |
Uric Acid, µM | 0.31 | 0.10 to 0.50 | ** |
Bicarbonates, mM | −0.22 | −0.43 to 0.01 | * |
Protein intake, g/kg/day | 0.06 | −0.21 to 0.31 | ns |
Triglycerides | 0.17 | −0.02 to 0.35 | ns |
HDL-cholesterol, mmol/L | −0.10 | −0.28 to 0.09 | ns |
LDL-cholesterol, mmol/L | −0.16 | −0.34 to 0.03 | ns |
TMA, µmol/L | −0.14 | −0.32 to 0.06 | ns |
Choline, µmol/L | 0.18 | −0.01 to 0.36 | ns |
Betain, µmol/L | −0.05 | −0.23 to 0.15 | ns |
Carnitine, µmol/L | 0.20 | 0.01 to 0.38 | * |
Analyte | Controls | CKD Patients | Hemodialysis | p-Value | ||
---|---|---|---|---|---|---|
Stage 1–2 | Stage 3a–3b | Stage 4–5 | ||||
N | 18 | 49 | 31 | 15 | 11 | |
Choline, µmol/L | 1.10 ± 0.22 a | 1.03 ± 0.21 a | 1.11 ± 0.27 a | 1.31 ± 0.28 a | 3.32 ± 1.02 b | <0.0001 |
Betain, µmol/L | 40.15 [29.98–56.25] | 29.90 [31.33–38.50] | 32.20 [22.40–39.20] | 33.40 [21.30–37.40] | 40.13 [24.98–58.43] | 0.0516 |
Carnitine, µmol/L | 52.83 ± 18.55 a | 49.71 ± 13.07 a | 57.58 ± 16.91 a | 79.44 ± 31.62 b | 21.11 ± 7.73 c | <0.0001 |
TMA, µmol/L | 0.28 [0.26–0.32] a | 0.27 [0.25–0.31] a | 0.21 [0.18–0.28] b | 0.23 [0.21–0.28] a,b | ND | <0.0001 |
Group | Parameter | mGFR, mL/min/1.73 m2 | FR Na % | pTMAO µmol/L | Cl TMAO mL/min/1.73 m2 | FE TMAO % | pCreat µmol/L | Cl Creatinine mL/min/1.73m2 | FE Creat % | pUrea mmol/L | Cl Urea mL/min/1.73m2 | FE Urea % |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Controls | median | 98 | 99.4 | 2.4 | 109 | 103 | 72 | 125 | 127 | 4.8 | 53 | 51 |
n = 5 | IQR | [91–105 | [98.8–99.6] | [2.1–30.7] | [50–145] | [55–144] | [68–82] | [104–148] | [114–141] | [3.7–5.5] | [39–77] | [42–76] |
CKD stages 1–2 | median | 73 | 99.4 | 3.5 | 71 | 106 | 94 | 94 | 133 | 5.5 | 38 | 56 |
n = 19 | IQR | [67–79] | [99.0–99.7] | [2.4–4.9] | [57–89] | [86–118] | [84–109] | [81–116] | [120–146] | [3.8–6.4] | [31–52] | [46–66] |
CKD stages 3–5 | median | 51 | 99.1 | 9.2 | 55 | 108 | 123 | 73 | 153 | 8.3 | 30 | 61 |
n = 8 | IQR | [46–55] | [97.9–99.5] | [5.4–14.0] | [43–67] | [98–130] | [96–151] | [61–84] | [132–161] | [6.3–10.7] | [18–44] | [51–82] |
p-value | <0.0001 | 0.401 | 0.134 | 0.048 | 0.899 | 0.001 | 0.002 | 0.121 | 0.005 | 0.051 | 0.721 |
Analyte | Pre-Dialysis | Post-Dialysis | FR | p |
---|---|---|---|---|
TMAO, µmol/L | 90.84 ± 40.11 | 14.65 ± 10.39 | 84.91 ± 6.49 | <0.0001 |
Choline, µmol/L | 3.32 ± 1.02 | 1.76 ± 0.64 | 46.72 ± 14.30 | <0.0001 |
Betaine, µmol/L | 42.68 ± 17.34 | 16.34 ± 7.62 | 61.26 ± 10.53 | <0.0001 |
Carnitine, µmol/L | 21.11 ± 7.73 | 4.45 ± 1.50 | 77.89 ± 7.29 | <0.0001 |
Urea, mmol/L | 18.7 ± 6.93 | 3.97 ± 2.01 | 79.21 ± 5.66 | <0.0001 |
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Pelletier, C.C.; Croyal, M.; Ene, L.; Aguesse, A.; Billon-Crossouard, S.; Krempf, M.; Lemoine, S.; Guebre-Egziabher, F.; Juillard, L.; Soulage, C.O. Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate. Toxins 2019, 11, 635. https://doi.org/10.3390/toxins11110635
Pelletier CC, Croyal M, Ene L, Aguesse A, Billon-Crossouard S, Krempf M, Lemoine S, Guebre-Egziabher F, Juillard L, Soulage CO. Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate. Toxins. 2019; 11(11):635. https://doi.org/10.3390/toxins11110635
Chicago/Turabian StylePelletier, Caroline C., Mikael Croyal, Lavinia Ene, Audrey Aguesse, Stephanie Billon-Crossouard, Michel Krempf, Sandrine Lemoine, Fitsum Guebre-Egziabher, Laurent Juillard, and Christophe O. Soulage. 2019. "Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate" Toxins 11, no. 11: 635. https://doi.org/10.3390/toxins11110635
APA StylePelletier, C. C., Croyal, M., Ene, L., Aguesse, A., Billon-Crossouard, S., Krempf, M., Lemoine, S., Guebre-Egziabher, F., Juillard, L., & Soulage, C. O. (2019). Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate. Toxins, 11(11), 635. https://doi.org/10.3390/toxins11110635