Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients
Abstract
:1. Introduction
2. Methods
2.1. Study Design and Population
2.2. Exposure Definition
2.3. Assessement of Plasma and Urinary Magnesium
2.4. Assessment of Dietary Magnesium Intake
2.5. Assessment of Covariates
2.6. Statistical Analyses
3. Results
3.1. Baseline Characteristics
3.2. Association of PPI Use with Plasma Magnesium and 24-h urinary Magnesium Excretion
3.3. Association of PPI Use with Hypomagnesaemia
3.4. Dose–Response Analyses
3.5. Sensitivity Analyses for Risk of Hypomagnesaemia
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | Total Population | Non-PPI Users | PPI Users | P |
---|---|---|---|---|
Number of subjects, n (%) | 689 (100) | 300 (43.5) | 389 (56.5) | n/a |
Demographics | ||||
Age, year | 53 ± 13 | 51 ± 13 | 54 ± 12 | 0.001 |
Men, n (%) | 395 (57.3) | 177 (59.0) | 218 (56.0) | 0.4 |
BMI, kg/m2 | 26.6 ± 4.8 | 25.9 ± 4.6 | 27.1 ± 4.8 | 0.002 |
Diabetes Mellitus, n (%) | 165 (23.9) | 55 (18.3) | 110 (28.3) | 0.002 |
History of CV disease, n (%) | 274 (39.8) | 92 (30.7) | 182 (46.8) | <0.001 |
Time since transplantation, year | 5.5 (1.9–12.1) | 9.6 (4.1–15.0) | 4.2 (1.1–8.7) | <0.001 |
Lifestyle parameters | ||||
Current smoker, n (%) | 84 (13.0) | 35 (12.4) | 49 (13.6) | 0.7 |
Alcohol consumer, n (%) | 436 (70.3) | 198 (72.8) | 238 (68.4) | 0.2 |
Magnesium intake, mg/day | 329.9 ± 88.7 | 333.0 ± 89.2 | 327.6 ± 88.4 | 0.5 |
Renal function parameters | ||||
eGFR, mL/min/1.73 m2 | 52.3 ± 20.2 | 55.1 ± 19.9 | 50.2 ± 20.1 | 0.002 |
Serum creatinine, µmol/L | 124 (100–160) | 119 (98–152) | 128 (101–168) | 0.03 |
Proteinuria (≥0.5 g/24 h), n (%) | 157 (22.9) | 71 (23.7) | 86 (22.2) | 0.7 |
Laboratory parameters | ||||
Hypomagnesaemia, n (%) | 145 (21.0) | 43 (14.3) | 102 (26.2) | <0.001 |
Plasma magnesium, mmol/L | 0.77 ± 0.11 | 0.79 ± 0.09 | 0.76 ± 0.11 | <0.001 |
24-h urinary magnesium excretion, mmol/24 h | 3.3 (2.3–3.3) | 3.8 (2.8–4.8) | 3.1 (2.0–3.9) | <0.001 |
Serum potassium, mmol/L | 3.98 ± 0.46 | 3.97 ± 0.47 | 3.99 ± 0.46 | 0.6 |
Serum calcium, mmol/L | 2.40 ± 0.15 | 2.40 ± 0.15 | 2.40 ± 0.15 | 0.8 |
PTH, pmol/L | 9.0 (6.0–14.8) | 8.7 (6.0–13.6) | 9.2 (5.9–16.3) | 0.2 |
Glucose, mmol/L | 5.3 (4.8–6) | 5.2 (4.7–5.8) | 5.3 (4.8–6.2) | 0.01 |
HbA1c, mmol/mol | 40 (37–44) | 39 (36–42) | 41 (38–45) | <0.001 |
Medication use | ||||
Mycophenolate mofetil, n (%) | 452 (65.6) | 178 (59.3) | 274 (70.4) | 0.002 |
Tacrolimus, n (%) | 124 (18.0) | 49 (16.3) | 75 (19.3) | 0.3 |
Cyclosporine, n (%) | 272 (39.5) | 97 (32.3) | 175 (45.0) | 0.001 |
Sirolimus, n (%) | 13 (2.0) | 8 (2.8) | 5 (1.4) | 0.3 |
Prednisolone, n (%) | 682 (99.0) | 298 (99.3) | 384 (98.7) | 0.7 |
Loop diuretics, n (%) | 160 (23.2) | 41 (13.7) | 119 (30.6) | <0.001 |
Thiazide diuretics, n (%) | 120 (17.4) | 53 (17.7) | 67 (17.4) | 0.9 |
H2-receptor antagonists, n (%) | 18 (2.6) | 17 (5.7) | 1 (0.3) | <0.001 |
Combination therapy | ||||
MMF + Tac + pred, n (%) | 78 (11.3) | 32 (10.7) | 46 (11.8) | 0.6 |
MMF + Cyclo + pred, n (%) | 175 (25.4) | 51 (17.0) | 124 (31.9) | <0.001 |
MMF + Tac, n (%) | 81 (11.8) | 33 (11.0) | 48 (12.3) | 0.6 |
MMF + Pred, n (%) | 447 (64.9) | 176 (58.7) | 271 (69.7) | 0.003 |
MMF + Cyclo, n (%) | 177 (25.7) | 52 (17.3) | 125 (32.1) | <0.001 |
Cyclo + Pred, n (%) | 269 (39.0) | 96 (32.0) | 173 (44.5) | 0.001 |
Tac + Pred, n (%) | 120 (17.4) | 48 (16.0) | 72 (18.5) | 0.4 |
Plasma Magnesium, mmol/L | Urinary Magnesium Excretion, mmol/24 h | |||||
---|---|---|---|---|---|---|
β | 95% CI | P | β | 95% CI | P | |
Crude | −0.03 | −0.04; −0.01 | 0.001 | −0.86 | −1.10; −0.06 | <0.001 |
Multivariable model | −0.02 | −0.04; −0.003 | 0.02 | −0.82 | −1.07; −0.57 | <0.001 |
Hypomagnesaemia | |||
---|---|---|---|
N = 689 | Odds Ratio | 95% CI | P |
Crude | 2.12 | 1.43–3.15 | <0.001 |
Multivariable model | 2.00 | 1.21–3.31 | 0.007 |
Categories of PPI Use | |||||||
---|---|---|---|---|---|---|---|
No PPI | Low PPI Dose | High PPI Dose | |||||
Number of subjects | 300 | 251 | 138 | ||||
Odds ratio (95% CI) | P | Odds ratio (95% CI) | P | Odds ratio (95% CI) | P | P-Trend | |
Hypomagnesaemia | |||||||
Crude | 1.00 (reference) | n/a | 1.92 (1.25–2.96) | 0.003 | 2.53 (1.55–4.11) | <0.001 | <0.001 |
Multivariable model | 1.00 (reference) | n/a | 1.79 (1.04–3.08) | 0.04 | 2.46 (1.32–4.57) | 0.005 | 0.004 |
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Douwes, R.M.; Gomes-Neto, A.W.; Schutten, J.C.; van den Berg, E.; de Borst, M.H.; Berger, S.P.; Touw, D.J.; Hak, E.; Blokzijl, H.; Navis, G.; et al. Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients. J. Clin. Med. 2019, 8, 2162. https://doi.org/10.3390/jcm8122162
Douwes RM, Gomes-Neto AW, Schutten JC, van den Berg E, de Borst MH, Berger SP, Touw DJ, Hak E, Blokzijl H, Navis G, et al. Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients. Journal of Clinical Medicine. 2019; 8(12):2162. https://doi.org/10.3390/jcm8122162
Chicago/Turabian StyleDouwes, Rianne M., António W. Gomes-Neto, Joëlle C. Schutten, Else van den Berg, Martin H. de Borst, Stefan P. Berger, Daan J. Touw, Eelko Hak, Hans Blokzijl, Gerjan Navis, and et al. 2019. "Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients" Journal of Clinical Medicine 8, no. 12: 2162. https://doi.org/10.3390/jcm8122162
APA StyleDouwes, R. M., Gomes-Neto, A. W., Schutten, J. C., van den Berg, E., de Borst, M. H., Berger, S. P., Touw, D. J., Hak, E., Blokzijl, H., Navis, G., & Bakker, S. J. L. (2019). Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients. Journal of Clinical Medicine, 8(12), 2162. https://doi.org/10.3390/jcm8122162