Gut Microbiota’s Oxalate-Degrading Activity and Its Implications on Cardiovascular Health in Patients with Kidney Failure: A Pilot Prospective Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Sample Size
2.3. Study Participants
2.4. Sample Collection
2.5. Clinical and Routine Laboratory Measurements
2.6. Determination of ODA in Feces
2.7. Measurement of POx Concentration
2.8. Determination of Plasma Malondialdehyde and Antioxidant Markers
2.9. Cytokine’s Measurements
2.10. Total Serum Indoxyl Sulfate Determination
2.11. Endpoint and Definition of CVD Events
2.12. Statistical Analysis
3. Results
3.1. Baseline Characteristics of the Study Participants
3.2. Microbiota’s ODA and Its Association with Examined Markers in the Entire Study Cohort
3.3. Microbiota’s ODA and CVD Events in Patients with Kidney Failure
3.4. Exploring the Link between Total Fecal ODA and CVD Events in Patients Undergoing KRT
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical and Laboratory Data | Control Group (n = 18) | Study Group (n = 32) | p-Value |
---|---|---|---|
Demographic and clinical parameters | |||
Male sex, n (%) | 6 (33.4%) | 18 (56.2%) | 0.12 |
Age, years | 46.4 ± 10.9 | 49.1 ± 13.4 | 0.54 |
BMI, kg/m2 | 23.8 ± 4.2 | 24.4 ± 3.9 | 0.31 |
Systolic blood pressure, mm Hg | 116.2 ± 10.9 | 128.9 ± 12.2 | 0.006 |
Diastolic blood pressure, mm Hg | 73.2 ± 8.8 | 82.1 ± 10.3 | 0.003 |
Time on dialysis, months | 38.5 (22–135) | ||
Anuria, n (%) | 11 (34.4%) | ||
Serum creatinine (µmol/L) | 87 (82.02–102.5) | 751 (575.7–968.4) | <0.0001 |
Serum urea | 5.4 (4.3–6.1) | 22.5 (17.7–31.3) | <0.0001 |
GFR (mL/min/1.73 m2) | 76.4 (66.1–79.8) | 4.5 (3.5–7.0) | <0.0001 |
Serum albumin, g/L | 42.2 (41.05–46.1) | 40.6 (38.5–41.6) | 0.003 |
Hb, g/L | 123 (119.5–133) | 105.5 (94–125) | 0.003 |
Glucose, mmol/L | 5.4 (4.7–5.7) | 4.9 (4.02–5.9) | 0.47 |
Calcium, mmol/L | 2.37 ± 0.1 | 2.29 ± 0.18 | 0.019 |
Phosphorus, mmol/L | 1.05 (0.9–1.1) | 1.99 (1.5–2.6) | <0.0001 |
Potassium, mmol/L | 4.1 (3.8–4.4) | 5.9 (5.2–6.9) | 0.0001 |
Uric acid (mmol/L) | 286.7 (146.4–374) | 329.4 (294.5–389.3) | 0.007 |
Lipid profile parameters | |||
TC, mmol/L | 4.9 (4.6–5.3) | 5.3 (4.5–6.6) | 0.15 |
Triglycerides, mmol/L | 1.12 (0.9–1.6) | 1.56 (1.1–2.5) | 0.05 |
LDL-C, mmol/L | 2.3 (1.5–2.9) | 3.1 (2.5–3.5) | 0.05 |
HDL-C, mmol/L | 1.5 (1.3–1.65) | 1.2 (1.07–1.56) | 0.04 |
AIP | 2.7 (1.9–3.1) | 3.2 (2.5–4.9) | 0.01 |
Oxidative stress markers | |||
MDA, mmol/L | 119 (101.3–128.4) | 256.4 (134.6–480.7) | <0.0001 |
Ceruloplasmin, g/L | 0.22 (0.16–0.31) | 0.13 (0.09–0.19) | 0.003 |
Transferrin, g/L | 5.2 (4.5–5.8) | 2.2 (1.5–2.6) | <0.0001 |
SH groups, mmol/L | 2.22 ± 1.1 | 1.65 ± 0.69 | 0.02 |
OSI, CU | 1.04 ± 0.04 | 3.8 ± 2.1 | <0.0001 |
Proinflammatory markers, tIS and POx concentrations | |||
CRP, mg/L | 4.2 (2.9–10.9) | 11.6 (7.7–17.8) | 0.001 |
IL-6, pg/mL | 0.8 (0.5–1.3) | 2.5 (1.9–6.1) | 0.0001 |
MCP-1, pg/mL | 200.0 (159.7–239.1) | 327.5 (281.2–344) | <0.0001 |
tIS, μmol/L | 0.85 (0.5–2.6) | 39.8 (20–51.3) | <0.0001 |
POx, µmol/L | 4.5 (3.09–7.3) | 39.3 (26.2–49.5) | <0.0001 |
Medications, n (%) | |||
ACE inhibitors/RAAS blockers | 25 (78%) | ||
Beta blockers | 18 (56.2%) | ||
Calcium channel blockers | 7 (21.9%) | ||
Iron supplementation | 19 (59.3%) | ||
Erythropoietins | 23 (71.8%) | ||
Calcium-based phosphate binders | 9 (28.1%) | ||
Non-calcium phosphate binders | 3 (9.4%) | ||
Statins | 11 (34.4%) |
Univariate Cox Regression Analysis | Multivariate Cox Regression Analysis | |||||
---|---|---|---|---|---|---|
Variable | Wald χ2 | p-Value | HR (95% CI) | Wald χ2 | p-Value | HR (95% CI) |
Age, years | 2.15 | 0.041 | 1.05 (1.02; 1.09) | 1.11 | 0.290 | 1.01 (0.93; 1.26) |
Systolic blood pressure, mm Hg | 0.09 | 0.765 | 0.99 (0.91–1.08) | |||
Diastolic blood pressure, mm Hg | 0.90 | 0.343 | 0.95 (0.86; 1.05) | |||
Male sex | 1.88 | 0.171 | 0.37 (0.09; 1.54) | |||
Dialysis modality | 1.29 | 0.257 | 2.30 (0.55; 9.6) | |||
Dialysis duration, months | 3.58 | 0.048 | 1.11 (1.00; 1.27) | 1.83 | 0.061 | 1.31 (0.95; 2.1) |
Anuria | 2.03 | 0.064 | 0.86 (0.17; 4.3) | |||
Obesity (BMI ≥ 30 kg/m2) | 6.28 | 0.012 | 6.22 (1.21; 10.1) | 5.21 | 0.018 | 1.63 (1.1; 2.4) |
Glucose_blood | 0.05 | 0.825 | 0.93 (0.48; 1.79) | |||
Ca, mmol/L | 2.81 | 0.082 | 0.93 (0.49; 1.77) | |||
Triglycerides, mmol/L | 5.82 | 0.015 | 1.39 (1.09; 2.36) | 3.59 | 0.022 | 1.46 (1.1; 3.4) |
HDL-C, mmol/L | 3.05 | 0.048 | 0.06 (0.008; 0.9) | 2.71 | 0.039 | 0.05 (0.01; 0.89) |
MDA, mmol/L | 3.41 | 0.044 | 1.27 (1.0; 8.8) | 2.29 | 0.066 | 1.25 (0.97; 7.16) |
Ceruloplasmin, g/L | 1.86 | 0.172 | 0.91 (0.54; 1.3) | |||
tIS, μmol/L | 4.26 | 0.018 | 2.15 (1.18; 3.22) | 3.79 | 0.026 | 1.73 (1.06; 4.11) |
POx (µmol/L) | 5.61 | 0.001 | 4.66 (1.2; 16.5) | 3.12 | 0.017 | 3.65 (1.3; 8.9) |
IL-6, pg/mL | 1.83 | 0.045 | 1.13 (1.01; 1.28) | 1.56 | 0.068 | 2.43 (0.94; 6.2) |
MCP-1, pg/mL | 1.61 | 0.038 | 1.11 (1.07; 1.19) | 1.37 | 0.172 | 1.05 (0.97; 1.13) |
CRP, g/L | 0.17 | 0.680 | 1.02 (0.95; 1.08) | |||
Total fecal ODA, %/0.01 g | 5.51 | 0.001 | 9.41 (2.3; 19.4) | 3.89 | 0.003 | 4.1 (1.4; 16.3) |
Total Fecal ODA Status | p-Value | ||
---|---|---|---|
Positive (≥1%/0.01 g of Feces) (n = 17) | Negative (≤−1%/0.01 g of Feces) (n = 15) | ||
Lipid profile parameters | |||
TC, mmol/L | 5.3 (4.8–6.0) | 5.8 (4.1–6.6) | 0.89 |
Triglycerides, mmol/L | 1.4 (102.0–1.7) | 2.6 (1.6–3.1) | 0.002 |
LDL-C, mmol/L | 2.8 (2.4–3.5) | 2.9 (1.8–3.8) | 0.9 |
HDL-C, mmol/L | 1.45 (1.3–1.8) | 1.03 (0.9–1.2) | 0.0005 |
AIP | 2.8 (1.8–3.5) | 3.1 (2.3–4.0) | 0.007 |
Oxidative stress markers | |||
MDA, mmol/L | 179.5 (112.2–282.0) | 474.3 (250.1–522.4) | 0.008 |
Ceruloplasmin, g/L | 0.18 (0.12–0.25) | 0.09 (0.07–0.14) | 0.003 |
Transferrin, g/L | 2.1 (1.5–2.7) | 2.3 (1.8–2.6) | 0.74 |
SH groups, mmol/L | 1.65 ± 0.4 | 1.66 ± 0.3 | 0.95 |
OSI, CU | 2.6 ± 1.5 | 5.2 ± 2.6 | 0.001 |
Proinflammatory markers, tIS and POx concentrations | |||
CRP, mg/L | 4.9 (3.3–12.9) | 12.5 (10.3–15.1) | 0.03 |
IL-6, pg/mL | 0.18 (0.1–1.4) | 2.1 (0.1–6.6) | 0.01 |
MCP-1, pg/mL | 285.6 (234.4–315.6) | 342.0 (330.0–418.1) | 0.0003 |
tIS, μmol/L | 23.5 (15.0–42.2) | 63.8 (39.8–95.0) | 0.0001 |
POx, µmol/L | 19.4 (4.7–30.7) | 49.5 (30.3–70.5) | <0.0001 |
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Stepanova, N.; Tolstanova, G.; Aleksandrova, I.; Korol, L.; Dovbynchuk, T.; Driianska, V.; Savchenko, S. Gut Microbiota’s Oxalate-Degrading Activity and Its Implications on Cardiovascular Health in Patients with Kidney Failure: A Pilot Prospective Study. Medicina 2023, 59, 2189. https://doi.org/10.3390/medicina59122189
Stepanova N, Tolstanova G, Aleksandrova I, Korol L, Dovbynchuk T, Driianska V, Savchenko S. Gut Microbiota’s Oxalate-Degrading Activity and Its Implications on Cardiovascular Health in Patients with Kidney Failure: A Pilot Prospective Study. Medicina. 2023; 59(12):2189. https://doi.org/10.3390/medicina59122189
Chicago/Turabian StyleStepanova, Natalia, Ganna Tolstanova, Iryna Aleksandrova, Lesya Korol, Taisa Dovbynchuk, Victoria Driianska, and Svitlana Savchenko. 2023. "Gut Microbiota’s Oxalate-Degrading Activity and Its Implications on Cardiovascular Health in Patients with Kidney Failure: A Pilot Prospective Study" Medicina 59, no. 12: 2189. https://doi.org/10.3390/medicina59122189