Vitamin C Depletion and All-Cause Mortality in Renal Transplant Recipients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Renal Transplant Characteristics
2.3. Measurements
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Association of Plasma Vitamin C Concentration with Clinical Variables
3.3. Prospective Analyses
3.4. Mediation Analyses
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Appendix
References
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Variables | All Patients | Vitamin C (Ln), µmol/L | |||
---|---|---|---|---|---|
Std. β | p Value | ||||
No. of patients | 598 | - | - | ||
Vitamin C, µmol/L | 44 (31–55) | - | - | ||
Demographics | |||||
Age, years | 51 ± 12 | −0.05 * | 0.23 * | ||
Sex (male), n (%) | 328 (54) | −0.18 * | <0.001 * | ||
Ethnicity (caucasian), n (%) | 577 (96) | −0.02 | 0.60 | ||
Body Composition | |||||
Body surface area, m2 | 1.87 ± 0.19 | −0.04 | 0.22 | ||
Body mass index, kg/m2 | 26.0 ± 4.3 | −0.08 | 0.06 | ||
Primary Renal Diseases | −0.02 | 0.61 | |||
Primary glomerulonephritis, n (%) | 169 (28) | - | - | ||
Glomerulonephritis due to vascular or autoimmune disease, n (%) | 36 (6) | - | - | ||
Tubulointerstitial nephritis and pyelonephritis, n (%) | 92 (15) | - | - | ||
Polycystic kidney disease, n (%) | 106 (18) | - | - | ||
Dysplasia and hypoplasia, n (%) | 21 (4) | - | - | ||
Renovascular disease, n (%) | 32 (5) | - | - | ||
Diabetic nephropathy, n (%) | 22 (4) | - | - | ||
Hereditary diseases and other, n (%) | 117 (20) | - | - | ||
Tobacco Use | −0.08 | 0.06 | |||
Never smoker, n (%) | 214 (35) | - | - | ||
Ex-smoker, n (%) | 251 (42) | - | - | ||
Current smoker, n (%) | 131 (21) | - | - | ||
Blood Pressure | |||||
Systolic blood pressure, mmHg | 153 ± 22 | −0.11 | 0.004 | ||
Diastolic blood pressure, mmHg | 89 ± 9 | −0.11 | 0.01 | ||
Use of ACE-inhibitor or aII-antagonist, n (%) | 201 (33) | 0.07 | 0.11 | ||
Use of beta-blocker, n (%) | 368 (61) | −0.07 | 0.11 | ||
Prior History of CV Disease | |||||
History of MI, n (%) | 48 (8) | −0.01 | 0.75 | ||
History of TIA/CVA, n (%) | 32 (5) | −0.04 | 0.36 | ||
Transplantation | |||||
Time since transplantation, years | 5.9 (2.6–11.4) | 0.20 | <0.001 | ||
Dialysis vintage, months | −0.14 | 0.001 | |||
141 (24) | - | - | |||
1–5 years | 363 (61) | - | - | ||
>5 years | 94 (16) | - | - | ||
Deceased donor, n (%) | 515 (86) | 0.02 | 0.61 | ||
Immunosuppressive Therapy | |||||
Prednisolone, mg/day | 10.0 (7.5–10.0) | −0.11 | 0.008 | ||
Use of calcineurin inhibitors | −0.09 | 0.02 | |||
Cyclosporine, n (%) | 386 (65) | - | - | ||
Tacrolimus, n (%) | 84 (14) | - | - | ||
None, n (%) | 128 (21) | - | - | ||
Use of antimetabolites | −0.06 | 0.19 | |||
Azathioprine, n (%) | 194 (32) | - | - | ||
Mycophenolic acid, n (%) | 247 (41) | - | - | ||
None, (%) | 157 (26) | - | - | ||
Use of m-TOR inhibitors, n (%) | 10 (2) | −0.10 | 0.02 | ||
Induction therapy | −0.20 | <0.001 | |||
Anti-thymocyte globulin, n (%) | 70 (12) | - | - | ||
Muromonab-CD3 , n (%) | 26 (4) | - | - | ||
Anti-CD25 monoclonal antibodies, n (%) | 10 (2) | - | - | ||
None, n (%) | 492 (82) | - | - | ||
Acute rejection treatment | −0.13 | 0.03 | |||
High doses of steroids, n (%) | 186 (31) | - | - | ||
Other rejection therapy, n (%) | 82 (14) | - | - | ||
Cumulative dose of prednisolone, grams | 21.3 (11.3–37.9) | 0.21 | <0.001 | ||
Ischemia Times | |||||
Cold ischemia time, hours | 22 (15–27) | 0.01 | 0.75 | ||
Total warm ischemia, minutes | 35 (30–45) | 0.02 | 0.72 | ||
Renal Allograft Function | |||||
eGFR, mL/min/1.73 m2 | 47 ± 15 | 0.11 | 0.009 | ||
Urinary protein excretion, g/24 h | 0.2 (0.0–0.5) | −0.06 | 0.22 | ||
Proteinuria (>0.5 g/24 h), n (%) | 166 (27) | −0.11 | 0.006 | ||
Inflammation | |||||
hs-CRP, mg/L | 2.0 (0.7–4.8) | −0.19 | <0.001 | ||
sICAM-1, ng/L | 602 (514–720) | −0.17 | <0.001 | ||
sVCAM-1, ng/L | 965 (772–1196) | −0.16 | <0.001 | ||
Lipids | |||||
Total colesterol, mmol/L | 5.6 ± 1.0 | 0.05 | 0.24 | ||
HDL colesterol, mmol/L | 1.0 ± 0.3 | 0.11 | 0.004 | ||
LDL cholesterol, mmol/L | 3.5 ± 0.9 | 0.07 | 0.09 | ||
Triglycerides, mmol/L | 1.9 (1.4–2.6) | −0.13 | 0.001 | ||
Use of statins, n (%) | 295 (49) | 0.06 | 0.13 | ||
Oxidative Stress | |||||
Gamma glutamate, U/L | 24 (18–39) | −0.10 | 0.02 | ||
Alkaline phophatase, U/L | 72 (57–94) | −0.21 | <0.001 | ||
Uric acid, mmol/L | 0.4 (0.3–0.5) | −0.08 | 0.05 | ||
Glucose Homeostasis | |||||
Insulin, µU/mL | 11 (7–16) | −0.08 | 0.04 | ||
Glucose, mmol/L | 4.5 (4.1–5.0) | −0.07 | 0.06 | ||
HbA1c, % | 6.5 ± 1.0 | −0.12 | 0.002 | ||
Diabetes, n (%) | 105 (17) | −0.11 | 0.008 | ||
Hematology | |||||
Leukocyte count, x 109/L | 8.5 ± 2.4 | −0.03 | 0.42 | ||
Hemoglobin, mmol/L | 8.5 ± 0.9 | 0.01 | 0.77 | ||
Platelets count, x 109/L | 231 ± 69 | −0.02 | 0.56 |
Vitamin C, Status | Vitamin C, Continuous | ||||||
---|---|---|---|---|---|---|---|
≤28 µmol/L n = 133 | >28 µmol/L n = 465 | 2log, µmol/L n = 598 | |||||
HR | 95% CI | p | Reference | HR | 95% CI | p | |
Model 1 | 1.95 | 1.35–2.81 | <0.001 | 1.00 | 0.71 | 0.59–0.87 | 0.001 |
Model 2 | 1.92 | 1.33–2.77 | 0.001 | 1.00 | 0.74 | 0.61–0.90 | 0.002 |
Model 3 | 1.88 | 1.28–2.76 | 0.001 | 1.00 | 0.76 | 0.62–0.94 | 0.011 |
Model 4 | 1.91 | 1.30–2.82 | 0.001 | 1.00 | 0.76 | 0.62–0.94 | 0.012 |
Model 5 | 1.80 | 1.22–2.65 | 0.003 | 1.00 | 0.79 | 0.64–0.98 | 0.030 |
Model 6 | 1.70 | 1.15–2.52 | 0.008 | 1.00 | 0.79 | 0.63–0.98 | 0.030 |
Model 7 | 1.74 | 1.18–2.57 | 0.005 | 1.00 | 0.78 | 0.63–0.97 | 0.024 |
Potential Mediator | Effect (Path) * | Multivariate Model ** | |
---|---|---|---|
Coefficient (95% CI) † | Proportion Mediated | ||
hs-CRP | Indirect effect (ab path) | −0.016 (−0.036; −0.004) | 16% *** |
Total effect (ab + c’ path) | −0.103 (−0.189; −0.010) | ||
sICAM-1 | Indirect effect (ab path) | −0.018 (−0.043; −0.003) | 17% *** |
Total effect (ab + c’ path) | −0.103 (−0.194; −0.016) | ||
sVCAM-1 | Indirect effect (ab path) | −0.015 (−0.040; −0.003) | 15% *** |
Total effect (ab + c’ path) | −0.103 (−0.200; −0.015) | ||
Combined inflammation | Indirect effect (ab path) | −0.033 (−0.065; −0.012) | 32% *** |
Total effect (ab + c’ path) | −0.103 (−0.191; −0.013) |
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Sotomayor, C.G.; Eisenga, M.F.; Gomes Neto, A.W.; Ozyilmaz, A.; Gans, R.O.B.; Jong, W.H.A.d.; Zelle, D.M.; Berger, S.P.; Gaillard, C.A.J.M.; Navis, G.J.; et al. Vitamin C Depletion and All-Cause Mortality in Renal Transplant Recipients. Nutrients 2017, 9, 568. https://doi.org/10.3390/nu9060568
Sotomayor CG, Eisenga MF, Gomes Neto AW, Ozyilmaz A, Gans ROB, Jong WHAd, Zelle DM, Berger SP, Gaillard CAJM, Navis GJ, et al. Vitamin C Depletion and All-Cause Mortality in Renal Transplant Recipients. Nutrients. 2017; 9(6):568. https://doi.org/10.3390/nu9060568
Chicago/Turabian StyleSotomayor, Camilo G., Michele F. Eisenga, Antonio W. Gomes Neto, Akin Ozyilmaz, Rijk O.B. Gans, Wilhelmina H.A. de Jong, Dorien M. Zelle, Stefan P. Berger, Carlo A. J.M. Gaillard, Gerjan J. Navis, and et al. 2017. "Vitamin C Depletion and All-Cause Mortality in Renal Transplant Recipients" Nutrients 9, no. 6: 568. https://doi.org/10.3390/nu9060568