Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics
2.2. Univariate Correlations Between Sevelamer Use and Other Variables
2.3. Association Between Sevelamer Use and Uremic Toxins
2.4. Association Between Sevelamer Use and dp-uc MGP
2.5. AssociationsBetween dp-uc MGP and Uremic Toxins
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Clinical Data
4.3. Biochemical Measurements
4.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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All Patients (n = 423) | Sevelamer Non-Users (n = 251, 59%) | Sevelamer Users (n = 172, 41%) | p-Value | |
---|---|---|---|---|
Demography and clinical characteristics | ||||
Age, years | 54 (43–63) | 56 (43–65) | 52 (43–61) | 0.01 |
Male sex, n (%) | 277 (66%) | 170 (68%) | 107 (62%) | 0.24 |
BMI, kg/m2 | 24.2 (22.0–26.6) | 23.6 (21.5–26.0) | 24.9 (22.5–27.8) | 0.01 |
Diastolic BP, mmHg | 80 (73–89) | 80 (74–89) | 79 (72–89) | 0.38 |
Systolic BP, mmHg | 140 (127–153) | 140 (125–153) | 140 (129–152) | 0.96 |
Dialysis vintage, months | 24.6 (6.1–42.6) | 24.2 (9.4–41.1) | 25.6 (1.7–49.8) | 0.68 |
Treatment | 0.82 | |||
Non-dialysis, n (%) | 37 (9%) | 22 (9%) | 15 (9%) | |
Hemodialysis, n (%) | 261 (62%) | 152 (60%) | 109 (63%) | |
Peritoneal dialysis, n (%) | 125 (29%) | 77 (31%) | 48 (28%) | |
Biochemical measurements | ||||
Hemoglobin, g/dL | 11.8 (1.6) | 11.6 (1.6) | 12.0 (1.6) | 0.06 |
Creatinine, mg/dL | 7.6 (5.9–9.3) | 7.3 (5.4–8.8) | 7.9 (6.4–10.2) | <0.001 |
Calcium, mg/dL | 9.1 (8.5–9.6) | 9.1 (8.5–9.6) | 9.1 (8.6–9.7) | 0.34 |
Phosphate, mg/dL | 4.6 (3.8–5.6) | 4.3 (3.6–5.3) | 5.0 (4.1–5.9) | <0.001 |
Serum albumin, g/L | 40.7 (36.0–45.1) | 41.7 (37.0–45.4) | 40.0 (35.0–44.8) | 0.05 |
Parathyroid hormone, ng/L | 168 (87–289) | 166 (81–269) | 173 (96–320) | 0.11 |
Uremic toxins | ||||
Indoxyl sulfate, μM | 101 (62–151) | 89 (55–136) | 123 (76–161) | <0.001 |
p-Cresyl sulfate, μM | 166 (112–230) | 164 (108–230) | 170 (119–226) | 0.60 |
TMAO, μM | 58 (34–99) | 50 (29–91) | 67 (44–120) | <0.001 |
Phenylacetylglutamine, μM | 64 (34–103) | 58 (28–88) | 76 (44–120) | <0.001 |
Vitamin K status | ||||
dp-ucMGP, pmol/L | 1050 (712–1565) | 952 (655–1353) | 1180 (837–1832) | <0.001 |
Medications | ||||
Ca-blocker, n (%) | 144 (34.0%) | 82 (32.7%) | 62 (36.0%) | 0.47 |
Beta-blocker, n (%) | 205 (48.6%) | 118 (47.2%) | 87 (50.6%) | 0.49 |
ACEi/ARB, n (%) | 204 (48.3%) | 124 (49.4%) | 80 (46.8%) | 0.60 |
Statin, n (%) | 202 (47.8%) | 125 (49.8%) | 77 (44.8%) | 0.31 |
PPI use, n (%) | 144 (34.1%) | 82 (32.7%) | 62 (36.3%) | 0.45 |
25-OH vitamin D use, n (%) | 198 (46.8%) | 127 (51.0%) | 71 (41.0%) | 0.06 |
CCPB, n (%) | 303 (71.6%) | 186 (74.1%) | 117 (68.0%) | 0.17 |
per 1-SD Increase in IndS | ||
---|---|---|
Coefficients | p-Value | |
Sevelamer use | 0.28 | 0.002 |
per 1-SD increase in age | −0.03 | 0.43 |
Sex, male vs. female | −0.04 | 0.64 |
Cohort | −0.13 | 0.36 |
CCPB use | 0.11 | 0.23 |
per 1-SD increase in phosphate | −0.03 | 0.53 |
per 1-SD increase in creatinine | 0.49 | <0.0001 |
per 1-SD increase in dialysis vintage | 0.15 | 0.004 |
per 1-SD Increase in PAG | ||
---|---|---|
Coefficients | p-Value | |
Sevelamer use | 0.20 | 0.05 |
per 1-SD increase in age | 0.11 | 0.02 |
Sex, male vs. female | −0.20 | 0.06 |
Cohort | −0.14 | 0.35 |
CCPB use | −0.05 | 0.66 |
per 1-SD increase in phosphate | −0.04 | 0.45 |
per 1-SD increase in creatinine | 0.36 | <0.0001 |
per 1-SD increase in dialysis vintage | 0.11 | 0.05 |
per 1-SD Increase in dp-uc MGP | ||
---|---|---|
Coefficients | p-Value | |
Sevelamer use | 0.36 | 0.002 |
per 1-SD increase in age | 0.23 | <0.0001 |
Sex, male vs. female | −0.06 | 0.61 |
Cohort | 0.13 | 0.46 |
CCPB use | −0.20 | 0.002 |
per 1-SD increase in phosphate | −0.007 | 0.90 |
per 1-SD increase in creatinine | 0.12 | 0.05 |
per 1-SD increase in dialysis vintage | 0.007 | 0.91 |
per 1-SD Increase in dp-uc MGP | ||
---|---|---|
Coefficients | p-Value | |
per 1-SD increase in PAG | 0.47 | <0.0001 |
Sevelamer use | 0.26 | 0.01 |
CCPB | −0.19 | 0.07 |
per 1-SD increase in age | 0.18 | <0.0001 |
Sex, male vs. female | 0.04 | 0.71 |
Cohort | 0.23 | 0.14 |
per 1-SD increase in phosphate | 0.02 | 0.71 |
per 1-SD increase in creatinine | −0.05 | 0.39 |
per 1-SD increase in dialysis vintage | −0.03 | 0.57 |
per 1-SD Increase in dp-uc MGP | ||
---|---|---|
Coefficients | p-Value | |
per 1-SD increase in TMAO | 0.16 | 0.002 |
Sevelamer use | 0.33 | 0.003 |
CCPB | −0.22 | 0.06 |
per 1-SD increase in age | 0.21 | <0.0001 |
Sex, male vs. female | −0.05 | 0.64 |
Cohort | 0.11 | 0.54 |
per 1-SD increase in phosphate | −0.01 | 0.81 |
per 1-SD increase in creatinine | 0.10 | 0.12 |
per 1-SD increase in dialysis vintage | −0.007 | 0.92 |
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Dai, L.; Meijers, B.K.; Bammens, B.; de Loor, H.; Schurgers, L.J.; Qureshi, A.R.; Stenvinkel, P.; Evenepoel, P. Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction? Toxins 2020, 12, 351. https://doi.org/10.3390/toxins12060351
Dai L, Meijers BK, Bammens B, de Loor H, Schurgers LJ, Qureshi AR, Stenvinkel P, Evenepoel P. Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction? Toxins. 2020; 12(6):351. https://doi.org/10.3390/toxins12060351
Chicago/Turabian StyleDai, Lu, Björn K. Meijers, Bert Bammens, Henriette de Loor, Leon J. Schurgers, Abdul Rashid Qureshi, Peter Stenvinkel, and Pieter Evenepoel. 2020. "Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?" Toxins 12, no. 6: 351. https://doi.org/10.3390/toxins12060351
APA StyleDai, L., Meijers, B. K., Bammens, B., de Loor, H., Schurgers, L. J., Qureshi, A. R., Stenvinkel, P., & Evenepoel, P. (2020). Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction? Toxins, 12(6), 351. https://doi.org/10.3390/toxins12060351