Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity
Abstract
:1. Introduction
2. Results
2.1. Impact on the Metabolomic and Lipidomic Fingerprint in Severe Obese Individuals with Chronic Kidney Disease
2.1.1. Cohort Characterization: Body Weight and Biochemical Analyses
2.1.2. De Novo Synthesis of Phospholipids and Fatty Acid Remodeling Were Significantly Increased in Patients with CKD
2.1.3. Short Chain TG Showed a Negative Correlation with eGFR in OD Patients
2.1.4. Essential Amino Acids Are Increased in Obese Patients with CKD
2.2. Bariatric Surgery Improves the Serum Lipidomic Profile and Metabolomic Fingerprint in Obese Patients with CKD
2.2.1. Diglycerides and Medium-Chain Triglycerides Presented a Positive Correlation with Uric Acid in Obese Patients with CKD after Surgery
2.2.2. Isoleucine and Proline Decreased in the Serum of CKD Patients with Obesity after Bariatric Surgery
2.3. Bariatric Surgery Decreased Levels of Valine and Glutamine in Urine from Patients with CKD
3. Discussion
4. Materials and Methods
4.1. Study Cohort
4.1.1. Bariatric Surgery
4.1.2. Clinical Parameters Tests
4.1.3. Study Design
4.1.4. Samples Collection
4.2. Lipidomic Untargeted Analysis in Serum Samples by Liquid Chromatography Coupled to Mass Spectrometry (LC-MS)
4.2.1. Lipidomic Extraction, Sample Preparation
4.2.2. UHPLC-ESI-Q-TOF-MS Analysis
4.2.3. MS Signals Processing
4.2.4. Data Pre-Treatment
4.2.5. Statistical Analysis
4.2.6. Annotation of Unknown Features
4.3. Polar Metabolites Untargeted Analysis in Serum and Urine Samples by Gas Chromatography Coupled to High-Resolution Accurate Mass Spectrometry (GC-HRAM-MS)
4.3.1. Extraction of Polar Metabolites, Sample Preparation
4.3.2. GC-HRAM-MS Analysis
4.3.3. MS Signals Processing for Serum Samples
4.3.4. MS Signals Processing for Urine Samples
4.3.5. Data Pre-Treatment
4.3.6. Statistical Analysis
4.3.7. Annotation of Unknown Features
4.4. Correlation, Curve ROC Test Analyses and Heatmaps
4.5. Lipidomic and Amino Acid Pathways
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group | |||
---|---|---|---|
Parameters | Patients without CKD | CKD Patients | |
CKD Patients before BS | CKD Patients after BS | ||
Acronym | O | OD | OD BS |
n | 14 | 11 | |
Age (years), mean ± SD (range) | 51.76 ± 10.92 (35–66) | 53.09 ± 15.16 (29–71) | 54.09 ± 15.16 |
Gender (Male/Female) (%) | 38.47/61.53 | 66.64/33.36 | 66.64/33.36 |
Body weight (kg), mean ± SD (range) | 120.51 ± 16.96 (84–152) | 116.72 ± 25.33 (93.5–170) | 81.07 ± 22.42 (65–125) # |
BMI (kg/m2), mean ± SD (range) | 42.9 ± 3.72 (36.48–50.0) | 41.9 ± 5.98 (36.6–53.3) | 28.6 ± 5.69 (22.68–39.78) # |
Diabetes mellitus (%) | 28.6 | 63.6 | 9.1 |
Hypertension (%) | 35.7 | 90.9 | 63.6 |
Lipid-lowering drugs (%) | 14.3 | 63.6 | 18.1 |
Glucose (mg/dL), median (range) | 100 (79–171) | 174 (98–299) * | 86 (67–141) # |
HbA1c (%), mean ± SD | 6.02 ± 0.72 | 7.46 ± 1.81 * | 5.55 ± 0.83 # |
Cholesterol (mg/dL), mean ± SD | 183 ± 34.74 | 194 ± 49.62 | 160 ± 41.70 # |
HDL (mg/dL), median (range) | 45.9 (35.0–94.0) | 35 (21.6–57.3) * | 45 (27–78) # |
LDL (mg/dL), mean ± SD | 103.63 ± 26.19 | 98.50 ± 37.70 | 89.27 ± 37.85 |
TG (mg/dL), mean ± SD | 183.46 ± 126.29 | 314.54 ± 106.16 * | 116.36 ± 45.82 # |
Uric acid (mg/dL), mean ± SD | 5.52 ± 0.83 | 7.10 ± 1.69 * | 5.64 ± 1.10 # |
Serum Creatinine (mg/dL), mean ± SD | 0.80 ± 0.18 | 1.16 ± 0.43 * | 1.03 ± 0.39 |
eGFR (mL/min), mean ± SD | 94.18 ± 20.35 | 73.02 ± 30.76 * | 80.72 ± 31.02 |
Proteinuria (g/24 h), median (range) | 0.14 (0.10–0.53) | 1.48 (0.77–11.40) * | 0.68 (0.34–3.78) # |
UACR (mg/g), median (range) | 7.6 (3.6–110.4) | 1004 (158.0–6825) * | 321.79 (38.69–3104) # |
O | OD | |||
---|---|---|---|---|
Highlighted | Relationship | Highlighted | Relationship | |
Glucose | Cer, PE, LysoPC, DG, TG | Positive | — | — |
Cholesterol | Cer, PS, PC | Positive | TG | Positive |
LDL | — | — | LysoPC | Positive |
Uric Acid | LysoPC, PC | Positive | TG | Positive |
Creatinine | SM, PC, LysoPC, TG | Negative SM, Positive PC, LysoPC, TG | TG | Positive |
eGFR | — | — | TG | Negative |
Proteinuria | — | — | DG, TG | Positive |
UACR | SM, PC | Positive | — | — |
OD BS | OD | |||
---|---|---|---|---|
Highlighted | Relationship | Highlighted | Relationship | |
Glucose | — | — | — | — |
Cholesterol | SM, LysoPC, PI | Positive | TG | Positive |
LDL | SM | Positive | LysoPC | Positive |
Uric Acid | DG, TG (medium) | Positive | TG (short) | Positive |
Creatinine | — | — | TG | Positive |
eGFR | — | — | TG | Negative |
Proteinuria | — | — | DG, TG | Positive |
UACR | — | — | — | — |
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Lanzon, B.; Martin-Taboada, M.; Castro-Alves, V.; Vila-Bedmar, R.; González de Pablos, I.; Duberg, D.; Gomez, P.; Rodriguez, E.; Orešič, M.; Hyötyläinen, T.; et al. Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity. Metabolites 2021, 11, 836. https://doi.org/10.3390/metabo11120836
Lanzon B, Martin-Taboada M, Castro-Alves V, Vila-Bedmar R, González de Pablos I, Duberg D, Gomez P, Rodriguez E, Orešič M, Hyötyläinen T, et al. Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity. Metabolites. 2021; 11(12):836. https://doi.org/10.3390/metabo11120836
Chicago/Turabian StyleLanzon, Borja, Marina Martin-Taboada, Victor Castro-Alves, Rocio Vila-Bedmar, Ignacio González de Pablos, Daniel Duberg, Pilar Gomez, Elias Rodriguez, Matej Orešič, Tuulia Hyötyläinen, and et al. 2021. "Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity" Metabolites 11, no. 12: 836. https://doi.org/10.3390/metabo11120836