Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Clinical Data
2.2. Breath H2 Measurement
2.3. Stool Water Content Measurement
2.4. Diarrhea Classification
2.5. Dietary Assessment
2.6. Statistical Analyses
3. Results
3.1. Clinical Parameters
3.2. Determinants of Exhaled H2
3.3. H2 and Diarrhea
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Abbreviations
BMI | Body Mass Index |
BSFS | Bristol Stool Form Scale |
CH4 | Methane |
CKD | Chronic Kidney Disease |
eGFR | Estimated glomerular filtration rate |
FFQ | Food Frequency Questionnaire |
GI | Gastrointestinal |
H2 | Hydrogen |
IBS | Irritable bowel syndrome |
KTR | Kidney Transplant Recipients |
MMF | Mycophenolate mofetil |
PPI | Proton-pump inhibitors |
RS | Resistant starch |
SCFA | Short-chain Fatty Acids |
SIBO | Small Intestinal Bacterial Overgrowth |
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Baseline Characteristics | Total (n = 424) | Exhaled H2, per Group | ||
---|---|---|---|---|
1.0–6.9 ppm (n = 151) | 7.0–19.9 ppm (n = 139) | ≥20.0 ppm (n = 134) | ||
Fermentation Parameter | ||||
H2, ppm | 11 (5.0–25.0) | 4.0 (2.0–5.0) | 11.0 (8.0–15.0) b | 33.5 (26.0–49.0) ab |
Demographics | ||||
Age, years | 55.4 ± 13.2 | 55.4 ± 13.7 | 57.2 ± 12.1 | 53.7 ± 13.5 |
Sex (male), n (%) | 258 (60.8) | 86 (57.0) | 84 (62.7) | 88 (63.3) |
Transplant vintage, years | 1.8 (1.0–7.1) | 2.0 (1.0–8.1) | 1.0 (0.6–5.0) | 1.1 (0.8–7.8) |
History of allograft rejection, n (%) | 69 (16.3) | 27 (17.8) | 19 (14.2) | 23 (16.5) |
Body Composition | ||||
Body mass index, kg/m2 | 27.7 ± 4.8 | 28.2 ± 5.6 | 28.1 ± 4.6 | 26.8 ± 3.9 a |
Waist circumference, cm | 99.5 ± 13.2 | 100.8 ± 13.6 | 100.8 ± 13.4 | 96.9 ± 12.1 ab |
Body fat percentage, % | 31.1 ± 9.8 | 32.3 ± 10.3 | 31.6 ± 9.8 | 29.3 ± 9.0 a |
Immunosuppressive Drug Use | ||||
MMF, n (%) | 311 (73.3) | 113 (74.8) | 100 (74.6) | 98 (70.5) |
Tacrolimus, n (%) | 333 (78.5) | 111 (73.5) | 112 (83.5) | 110 (79.1) |
Cyclosporine, n (%) | 38 (9.0) | 17 (11.3) | 12 (8.9) | 9 (6.5) |
Everolimus, n (%) | 10 (2.4) | 5 (3.3) | 3 (2.2) | 2 (1.4) |
Prednisolone, n (%) | 396 (93.4) | 141 (93.4) | 124 (92.5) | 131 (94.2) |
Azathioprine, n (%) | 24 (5.7) | 8 (5.3) | 6 (4.5) | 10 (7.2) |
Immunosuppressive Drug Trough Levels | ||||
MMF, ug/L | 2.3 ± 1.6 | 2.2 ± 1.7 | 2.2 ±1.4 | 2.5 ± 1.8 |
Tacrolimus, ug/L | 6.3 ± 2.5 | 5.9 ± 2.3 | 6.1 ± 2.2 | 6.8 ± 2.4 a |
Lifestyle | ||||
Current smoker, n (%) | 13 (3.1) | 7 (4.6) | 4 (3.0) | 2 (1.4) |
Alcohol consumption, g/day | 1.5 (0.0–7.9) | 1.7 (0.0–7.3) | 1.0 (0.2–9.2) | 1.6 (0.0–7.6) |
Glucose Homeostasis | ||||
Diabetes mellitus, n (%) | 82 (19.3) | 28 (18.5) | 32 (23.0) | 22 (16.4) |
Plasma glucose, mmol/L | 6.1 ± 1.7 | 6.2 ± 1.6 | 6.1 ± 1.8 | 6.0 ± 1.8 |
HbA1c, % | 6.0 ± 1.7 | 6.0 ± 0.9 | 6.0 ± 0.8 | 5.9 ± 0.9 |
Lipids | ||||
Total cholesterol, mmol/L | 4.6 ± 1.0 | 4.7 ± 1.0 | 4.7 ± 1.0 | 4.4 ± 1.1 |
HDL-cholesterol, mmol/L | 1.3 ± 0.4 | 1.4 ± 0.4 | 1.4 ± 0.4 | 1.3 ± 0.4 |
LDL-cholesterol, mmol/L | 2.9 ± 0.9 | 2.9 ± 0.9 | 3.0 ± 0.9 | 2.7 ± 0.9 |
Triglycerides, mmol/L | 1.8 ± 0.8 | 1.9 ± 0.9 | 1.9 ± 0.8 | 1.8 ± 0.9 |
Cardiovascular | ||||
SBP, mmHg | 137.4 ± 16.9 | 137.9 ± 16.2 | 137.2 ± 16.6 | 137.1 ± 16.6 |
DBP, mmHg | 79.9 ± 11.1 | 79.8 ± 10.7 | 80.2 ± 11.1 | 79.6 ± 11.4 |
Kidney Function | ||||
eGFR, mL/min/1.73 m2 | 49.8 ± 19.1 | 49.3 ± 18.9 | 49.5 ± 18.2 | 50.4 ± 5.9 |
Creatinine, µmol/L | 155.3 ± 124.3 | 149.9 ± 92.2 | 152.4 ± 110.9 | 163.9 ± 161.6 |
Urinary protein excretion, g/24 h | 0.1 ± 0.2 | 0.2 ± 0.3 | 0.1 ± 0.1 | 0.1 ± 0.2 |
Medication | ||||
Proton pump inhibitors, n (%) | 306 (72.2) | 96 (63.5) | 105 (78.4) a | 105 (75.5) a |
Statins, n (%) | 220 (51.9) | 80 (53.0) | 72 (53.7) | 68 (48.9) |
Antihypertensive, n (%) | 311 (73.3) | 106 (70.2) | 105 (78.4) | 100 (71.9) |
Diarrhea according to BSFS, n (%) * | 76 (33.0) | 24 (27.9) | 25 (36.2) | 27 (36.0) |
Evacuation episodes, n/day * | 2.1 ± 1.3 | 2.2 ± 1.3 | 2.2 ± 1.3 | 2.1 ± 1.3 |
Stool water content, % ** | 75.4 ± 6.3 | 73.8 ± 6.0 | 75.8 ± 7.0 | 77.7 ± 5.5 c |
Potential Determinants | Univariate | Multivariate * | ||
---|---|---|---|---|
Std. β | p | Std. β | p | |
Polysaccharides intake, g | 0.266 | <0.001 | 0.243 | 0.01 |
Proton pump inhibitor use | 0.160 | <0.01 | 0.164 | 0.05 |
Mono and disaccharides intake, g | −0.188 | 0.01 | ||
Tacrolimus trough levels, ug/L | 0.133 | 0.02 | ||
Vitamin C intake, mg | −0.162 | 0.02 | ||
Total cholesterol, mmol/L | −0.106 | 0.03 | ||
LDL-cholesterol, mmol/L | −0.101 | 0.04 | ||
Waist circumference, cm | −0.098 | 0.05 |
Variable | OR (95% CI) | p |
---|---|---|
Log2 exhaled H2, ppm | 1.51 (1.07–2.14) | 0.02 |
Sex (male) | 1.10 (0.41–2.99) | 0.85 |
eGFR, mL/min/1.73 m2 | 0.95 (0.92–0.99) | 0.01 |
Transplant vintage, years | 0.99 (0.99–1.01) | 0.08 |
MMF use | 4.71 (1.24–17.77) | 0.02 |
Tacrolimus use | 0.25 (0.05–1.22) | 0.09 |
PPI, use | 1.09 (0.37–3.30) | 0.86 |
Polysaccharides intake, g | 0.99 (0.98–1.01) | 0.12 |
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Share and Cite
Rodrigues, F.G.; Swarte, J.C.; Douwes, R.M.; Knobbe, T.J.; Sotomayor, C.G.; Blokzijl, H.; Weersma, R.K.; Heilberg, I.P.; Bakker, S.J.L.; de Borst, M.H.; et al. Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients. J. Clin. Med. 2021, 10, 2854. https://doi.org/10.3390/jcm10132854
Rodrigues FG, Swarte JC, Douwes RM, Knobbe TJ, Sotomayor CG, Blokzijl H, Weersma RK, Heilberg IP, Bakker SJL, de Borst MH, et al. Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients. Journal of Clinical Medicine. 2021; 10(13):2854. https://doi.org/10.3390/jcm10132854
Chicago/Turabian StyleRodrigues, Fernanda Guedes, J. Casper Swarte, Rianne M. Douwes, Tim J. Knobbe, Camilo G. Sotomayor, Hans Blokzijl, Rinse K. Weersma, Ita P. Heilberg, Stephan J. L. Bakker, Martin H. de Borst, and et al. 2021. "Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients" Journal of Clinical Medicine 10, no. 13: 2854. https://doi.org/10.3390/jcm10132854