Fish Intake, Circulating Mercury and Mortality in Renal Transplant Recipients
Abstract
:1. Introduction
2. Methods
2.1. Design and Study Population
2.2. Assessment of Dietary Intake
2.3. Clinical Parameters
2.4. Laboratory Methods and Circulating Mercury Measurement
2.5. Calculations and Definitions
2.6. Statistical Analyses
3. Results
3.1. Baseline Characteristics
3.2. Prospective Analyses of Cardiovascular and All-Cause Mortality
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Baseline Characteristics | Overall RTRs (n = 604) | Categories of Amount of Fish Intake | |||
---|---|---|---|---|---|
0 g/day (n = 118) | 0–15 g/day (n = 241) | ≥15 g/day (n = 245) | p | ||
Fish and marine-derived n-3 PUFAs intake, and circulating mercury | |||||
Fish intake, g/day | 10.7 (3.9–18.3) † | 0.0 (0.0–0.0) | 7.8 (4.7–10.6) | 21.0 (17.0–31.9) | – |
EPA-DHA intake, mg/day | 103 (41–219) | 20 (11–36) | 70 (42–121) | 240 (170–334) | <0.001 |
Circulating mercury concentration, µg/L | 0.30 (0.14–0.63) | 0.22 (0.09–0.53) | 0.26 (0.13–0.62) | 0.37 (0.21–0.68) | <0.001 |
Demographics | |||||
Age, years | 53 ± 13 ‡ | 51 ± 13 | 52 ± 13 | 55 ± 12 | 0.02 |
Sex (male), n (%) | 346 (57) § | 70 (59) | 139 (58) | 137 (56) | 0.82 |
Caucasian ethnicity, n (%) | 602 (100) | 118 (100) | 239 (99) | 245 (100) | 0.22 |
Body composition | |||||
Body surface area, m2 | 1.94 ± 0.22 | 1.96 ± 0.22 | 1.94 ± 0.23 | 1.94 ± 0.20 | 0.81 |
Body mass index, kg/m2 | 26.1 (23.2–29.3) | 25.8 (23.0–29.3) | 26.1 (23.14–29.4) | 26.2 (23.6–29.3) | 0.22 |
Waist circumference, cms a | 99 ± 14 | 97 ± 14 | 99 ± 15 | 99 ± 14 | 0.32 |
Cardiovascular history | |||||
History of cardiovascular disease, n (%) b | 295 (49) | 55 (47) | 117 (49) | 123 (50) | 0.77 |
Heart rate, beats per minute c | 69 ± 12 | 68 ± 12 | 70 ± 12 | 68 ± 12 | 0.24 |
Arterial pressure d | |||||
Systolic blood pressure, mmHg | 136 ± 17 | 136 ± 15 | 135 ± 16 | 137 ± 18 | 0.72 |
Mean arterial pressure, mmHg | 101 ± 12 | 101 ± 11 | 100 ± 11 | 101 ± 13 | 0.60 |
Antihypertensive treatment | |||||
Use of antihypertensives, n (%) | 532 (88) | 104 (88) | 215 (89) | 213 (87) | 0.74 |
Number of antihypertensives | 1.8 ± 1.1 | 2.0 ± 1.2 | 1.8 ± 1.1 | 1.7 ± 1.0 | 0.15 |
Use of ACE-inhibitors or ARBs, n (%) | 198 (33) | 46 (39) | 73 (30) | 79 (32) | 0.25 |
Use of β-blockers, n (%) | 383 (63) | 79 (67) | 153 (64) | 151 (62) | 0.62 |
Use of calcium-antagonists, n (%) | 148 (25) | 30 (25) | 60 (25) | 58 (24) | 0.92 |
Lifestyle | |||||
Current smoker, n (%) a | 73 (12) | 15 (13) | 30 (12) | 28 (11) | 0.92 |
Alcohol consumption | <0.001 | ||||
None, n (%) | 24 (4) | 6 (5) | 8 (3) | 10 (4) | – |
≤10 g/day, n (%) | 420 (70) | 91 (77) | 187 (78) | 142 (58) | – |
>10 g/day, n (%) | 160 (27) | 21 (18) | 46 (19) | 93 (38) | – |
Total energy intake, kCal/day | 2170 ± 619 | 2227 ± 691 | 2147 ± 564 | 2165 ± 636 | 0.51 |
Renal allograft function | |||||
Creatinine, umol/L e | 123 (100–158) | 122 (98–166) | 125 (101–157) | 123 (101–156) | 0.97 |
Cystatine-C, mg/L f | 1.66 (1.32–2.20) | 1.70 (1.31–2.17) | 1.73 (1.36–2.33) | 1.60 (1.30–2.17) | 0.58 |
eGFR, mL/min/1.73 m2 f | 45 ± 18 | 46 ± 20 | 45 ± 18 | 45 ± 18 | 0.92 |
Proteinuria ≥ 0.5 g/24 h, n (%) d | 131 (22) | 28 (24) | 52 (22) | 51 (21) | 0.82 |
Lipids | |||||
Total cholesterol, mmol/L | 5.12 ± 1.11 | 5.12 ± 1.07 | 5.03 ± 1.07 | 5.20 ± 1.17 | 0.27 |
High-density lipoprotein-cholesterol, mmol/L d | 1.3 (1.1–1.6) | 1.3 (1.0–1.6) | 1.3 (1.0–1.6) | 1.3 (1.1–1.7) | 0.13 |
Low-density lipoprotein-cholesterol, mmol/L d | 2.98 ± 0.93 | 2.99 ± 0.86 | 2.94 ± 0.89 | 3.00 ± 1.01 | 0.73 |
Triglycerides, mmol/L | 1.68 (1.24–2.30) | 1.62 (1.19–2.28) | 1.71 (1.27–2.37) | 1.67 (1.23–2.25) | 0.71 |
Use of statins, n (%) | 318 (53) | 59 (50) | 119 (49) | 140 (57) | 0.19 |
Diabetes and glucose homeostasis | |||||
Diabetes mellitus, n (%) | 144 (24) | 23 (20) | 64 (27) | 57 (23) | 0.32 |
Plasma glucose, mmol/L e | 5.2 (4.8–6.0) | 5.3 (4.8–5.9) | 5.2 (4.7–6.0) | 5.3 (4.9–6.1) | 0.68 |
HbA1C, % g | 5.8 (5.5–6.2) | 5.8 (5.5–6.2) | 5.8 (5.4–6.3) | 5.8 (5.5–6.2) | 0.62 |
Insulin use, n (%) | 53 (9) | 6 (5) | 26 (11) | 21 (9) | 0.20 |
Inflammation and oxidative stress | |||||
Leukocyte count, per 109/L d | 8.1 ± 2.6 | 7.8 ± 2.3 | 8.4 ± 2.9 | 7.9 ± 2.5 | 0.02 |
High-sensitivity C-reactive protein, mg/L h | 1.6 (0.7–4.6) | 1.3 (0.5–3.6) | 1.6 (0.7–4.9) | 1.6 (0.8–4.7) | 0.17 |
Malondialdehyde, µmol/L f | 2.62 (1.99–3.86) | 2.50 (1.81–3.51) | 2.44 (1.99–3.79) | 2.77 (2.06–4.09) | 0.10 |
Renal transplantation characteristics | |||||
Time since transplantation, years | 5.7 (1.8–12.0) | 5.0 (1.7–10.6) | 5.6 (2.3–11.9) | 6.0 (1.4–12.2) | 0.65 |
Immunosuppressive therapy | |||||
Prednisolone dose, grams | 10.0 (7.5–10.0) | 10.0 (7.5–10.0) | 10.0 (7.5–10.0) | 10.0 (7.5–10.0) | 0.62 |
Sirolimus or rapamune use, n (%) | 9 (2) | 3 (3) | 2 (1) | 4 (2) | 0.42 |
Type of calcineurin inhibitor | 0.78 | ||||
None, n (%) | 260 (43) | 45 (38) | 104 (43) | 111 (45) | – |
Cyclosporine, n (%) | 242 (40) | 52 (44) | 95 (39) | 95 (39) | – |
Tacrolimus, n (%) | 102 (17) | 21 (18) | 42 (17) | 39 (16) | – |
Type of proliferation inhibitor | 0.13 | ||||
None, n (%) | 97 (16) | 22 (19) | 44 (18) | 31 (13) | – |
Azathioprine, n (%) | 101 (17) | 17 (14) | 33 (14) | 51 (21) | – |
Mycophenolic acid, n (%) | 406 (67) | 79 (67) | 164 (68) | 163 (67) | – |
Acute rejection treatment, n (%) | 156 (26) | 31 (26) | 57 (24) | 68 (28) | 0.58 |
Baseline Characteristics | Circulating Mercury Concentration, µg/L | |
---|---|---|
Std. β | p | |
Fish and marine-derived n-3 PUFAs intake, and circulating mercury | ||
Fish intake, g/day | 0.21 | <0.001 |
EPA-DHA intake, mg/day | 0.21 | <0.001 |
Circulating mercury concentration, µg/L | – | – |
Demographics | ||
Age, years | –0.04 | 0.31 |
Sex (male), n (%) | –0.05 | 0.19 |
Caucasian ethnicity, n (%) | 0.03 | 0.42 |
Body composition | ||
Body surface area, m2 | 0.06 | 0.14 |
Body mass index, kg/m2 | –0.01 | 0.85 |
Waist circumference, cms a | 0.01 | 0.82 |
Cardiovascular history | ||
History of cardiovascular disease, n (%) b | –0.05 | 0.22 |
Heart rate, beats per minute c | –0.03 | 0.51 |
Arterial pressure d | ||
Systolic blood pressure, mmHg | –0.01 | 0.72 |
Mean arterial pressure, mmHg | 0.04 | 0.33 |
Antihypertensive treatment | ||
Use of antihypertensives, n (%) | 0.02 | 0.67 |
Number of antihypertensives | <0.001 | 0.99 |
Use of ACE-inhibitors or ARBs, n (%) | –0.003 | 0.95 |
Use of β-blockers, n (%) | 0.01 | 0.85 |
Use of calcium-antagonists, n (%) | –0.02 | 0.65 |
Lifestyle | ||
Current smoker, n (%) a | 0.02 | 0.57 |
Alcohol consumption | 0.16 | <0.001 |
None, n (%) | – | – |
<10 g/day, n (%) | – | – |
>10 g/day, n (%) | – | – |
Total energy intake, kCal/day | 0.02 | 0.64 |
Renal allograft function | ||
Creatinine, umol/L e | 0.05 | 0.21 |
Cystatine-C, mg/L f | 0.02 | 0.59 |
eGFR, mL/min/1.73 m2 f | –0.06 | 0.16 |
Proteinuria ≥0.5 g/24 h, n (%) d | –0.04 | 0.39 |
Lipids | ||
Total cholesterol, mmol/L | 0.08 | 0.05 |
High-density lipoprotein-cholesterol, mmol/L d | 0.05 | 0.23 |
Low-density lipoprotein-cholesterol, mmol/L d | 0.04 | 0.33 |
Triglycerides, mmol/L | 0.02 | 0.62 |
Use of statins, n (%) | –0.01 | 0.90 |
Diabetes and glucose homeostasis | ||
Diabetes mellitus, n (%) | –0.05 | 0.24 |
Plasma glucose, mmol/L e | 0.001 | 0.98 |
HbA1C, % g | –0.05 | 0.21 |
Insulin use, n (%) | –0.02 | 0.59 |
Inflammation and oxidative stress | ||
Leukocyte count, per 109/L d | –0.01 | 0.81 |
High-sensitivity C-reactive protein, mg/L h | –0.01 | 0.78 |
Malondialdehyde, µmol/L f | 0.004 | 0.93 |
Renal transplantation characteristics | ||
Time since transplantation, years | –0.05 | 0.26 |
Immunosuppressive therapy | ||
Prednisolone dose, grams | –0.06 | 0.14 |
Sirolimus or rapamune use, n (%) | –0.03 | 0.53 |
Type of calcineurin inhibitor | 0.06 | 0.14 |
None, n (%) | – | – |
Cyclosporine, n (%) | – | – |
Tacrolimus, n (%) | – | – |
Type of proliferation inhibitor | 0.03 | 0.52 |
None, n (%) | – | – |
Azathioprine, n (%) | – | – |
Mycophenolic acid, n (%) | – | – |
Acute rejection treatment, n (%) | 0.07 | 0.11 |
Fish Intake, 10 g per day | Fish Intake, 10 g per day * | |||||
---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | |
Cardiovascular mortality | ||||||
Model 1 | 0.82 | 0.64–1.03 | 0.09 | 0.82 | 0.65–1.04 | 0.10 |
Model 2 | 0.80 | 0.62–1.03 | 0.08 | 0.80 | 0.62–1.04 | 0.09 |
Model 3 | 0.75 | 0.58–0.96 | 0.03 | 0.75 | 0.58–0.97 | 0.03 |
Model 4 | 0.76 | 0.60–0.98 | 0.04 | 0.77 | 0.59–0.99 | 0.04 |
Model 5 | 0.76 | 0.58–0.98 | 0.04 | 0.76 | 0.58–0.99 | 0.04 |
All-cause mortality | ||||||
Model 1 | 0.88 | 0.76–1.01 | 0.06 | 0.90 | 0.78–1.03 | 0.12 |
Model 2 | 0.87 | 0.75–1.00 | 0.05 | 0.89 | 0.77–1.03 | 0.11 |
Model 3 | 0.84 | 0.72–0.97 | 0.02 | 0.86 | 0.74–0.99 | 0.04 |
Model 4 | 0.84 | 0.73–0.98 | 0.02 | 0.87 | 0.75–1.00 | 0.05 |
Model 5 | 0.84 | 0.73–0.98 | 0.02 | 0.86 | 0.74–1.00 | 0.05 |
Marine-Derived n-3 PUFAs Intake, 100 mg per day | Marine-Derived n-3 PUFAs Intake, 100 mg per day * | |||||
---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | |
Cardiovascular mortality | ||||||
Model 1 | 0.83 | 0.66–1.03 | 0.09 | 0.83 | 0.66–1.04 | 0.10 |
Model 2 | 0.80 | 0.63–1.02 | 0.07 | 0.80 | 0.62–1.02 | 0.08 |
Model 3 | 0.75 | 0.58–0.96 | 0.02 | 0.75 | 0.58–0.96 | 0.02 |
Model 4 | 0.76 | 0.59–0.97 | 0.03 | 0.76 | 0.59–0.98 | 0.03 |
Model 5 | 0.77 | 0.60–0.99 | 0.04 | 0.78 | 0.60–1.00 | 0.05 |
All-cause mortality | ||||||
Model 1 | 0.87 | 0.76–0.99 | 0.03 | 0.88 | 0.77–1.01 | 0.06 |
Model 2 | 0.84 | 0.73–0.97 | 0.02 | 0.86 | 0.74–0.99 | 0.04 |
Model 3 | 0.81 | 0.70–0.94 | 0.01 | 0.83 | 0.71–0.96 | 0.01 |
Model 4 | 0.82 | 0.70–0.95 | 0.01 | 0.83 | 0.72–0.97 | 0.02 |
Model 5 | 0.83 | 0.72–0.96 | 0.01 | 0.85 | 0.73–0.98 | 0.03 |
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Sotomayor, C.G.; Gomes-Neto, A.W.; Gans, R.O.B.; De Borst, M.H.; Berger, S.P.; Rodrigo, R.; Navis, G.J.; Touw, D.J.; Bakker, S.J.L. Fish Intake, Circulating Mercury and Mortality in Renal Transplant Recipients. Nutrients 2018, 10, 1419. https://doi.org/10.3390/nu10101419
Sotomayor CG, Gomes-Neto AW, Gans ROB, De Borst MH, Berger SP, Rodrigo R, Navis GJ, Touw DJ, Bakker SJL. Fish Intake, Circulating Mercury and Mortality in Renal Transplant Recipients. Nutrients. 2018; 10(10):1419. https://doi.org/10.3390/nu10101419
Chicago/Turabian StyleSotomayor, Camilo G., António W. Gomes-Neto, Rijk O. B. Gans, Martin H. De Borst, Stefan P. Berger, Ramón Rodrigo, Gerjan J. Navis, Daan J. Touw, and Stephan J. L. Bakker. 2018. "Fish Intake, Circulating Mercury and Mortality in Renal Transplant Recipients" Nutrients 10, no. 10: 1419. https://doi.org/10.3390/nu10101419