Abstract: TH-PO478
Uric Acid-Lowering and Markers of CKD-Associated Mineral and Bone Disorder, Vascular Calcification, and Atherosclerosis
Session Information
- CKD: Epidemiology, Outcomes - Cardiovascular - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 303 CKD: Epidemiology, Outcomes - Cardiovascular
Authors
- Andrews, Emily, University of Colorado Denver, Aurora, Colorado, United States
- Perrenoud, Loni J., University of Colorado, Aurora, Colorado, United States
- Nowak, Kristen L., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States
- You, Zhiying, UC Denver, Aurora, Colorado, United States
- Pasch, Andreas, University Hospital Bern, Bern, Switzerland
- Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
- Kendrick, Jessica B., University of Colorado Denver and Denver Health Medical Center, Denver, Colorado, United States
- Jalal, Diana I., University of Colorado Denver Health Science Center, Aurora, Colorado, United States
Background
Chronic kidney disease (CKD)-associated mineral and bone disorder (MBD) is associated with vascular calcification and accelerated atherosclerosis. Higher uric acid reportedly suppresses 1,25-dihydroxyvitamin D (1,25(OH)2D). It is unknown if lowering serum uric acid improves markers of CKD-MBD, vascular calcification, or atherosclerosis in CKD.
Methods
Post-hoc analysis of a clinical trial randomizing 80 patients with stage 3 CKD and hyperuricemia to placebo vs allopurinol. Serum markers of CKD-MBD were measured. Protein expression of extra-renal 1α-hydroxylase was evaluated from participants' vascular endothelial cells. T50 and carotid intima-media thickness (CIMT) were measured as markers of serum calcification and vascular atherosclerosis, respectively. The Wilcoxon two-sample T-test was applied.
Results
Baseline characteristics between both study groups were similar except for significantly higher FGF-23 levels in the placebo group vs allopurinol. Allopurinol lowered serum uric acid levels significantly vs placebo (Table). We found no significant change in vitamin D metabolites or iPTH. Median FGF-23 levels increased slightly with allopurinol vs placebo (4.1(-10.2, 16.7) vs -1.83(-27.8, 19.1)), but this was not statistically significant. There was not a significant change in the expression of endothelial 1α-hydroxylase, serum T50, or CIMT.
Conclusion
These data suggest that factors other than uric acid play a more important role in the regulation of CKD-MBD including vitamin D metabolism and the progression of vascular calcification and atherosclerosis in patients with CKD.
Changes in CKD-MBD markers, CIMT, and T50 from baseline to the end of study visit (week 12)
| Variable | Placebo (n=34) | Allopurinol (n=29) | p value |
| Serum urate (mg/dL) | 0.09±1.58 | -3.28±1.42 | <0.0001 |
| Calcium (mg/dL) | -0.11±0.33 | -0.04±0.48 | 0.45 |
| Phosphorus (mg/dL) | -0.13±0.65 | 0.08±0.66 | 0.46 |
| 25 vitamin D (ng/mL) | 2.41±6.15 | 0.29±5.13 | 0.46 |
| 1,25 vitamin D (pg/mL) | 0.94±8.71 | -1.53±9.98 | 0.63 |
| 24,25 vitamin D (pg/mL) | 0.15±0.79 | -0.14±0.74 | 0.42 |
| iPTH (pg/mL) | 1.99±31.81 | 2.27±29.28 | 0.77 |
| FGF-23 (RU/mL) - median (IQR) | -1.83(-27.8, 19.1) | 4.1(-10.2, 16.7) | 0.35 |
| Serum T50 (min) | -2.5±41.3 | -13.9±57.8 | 0.42 |
| CIMT (mm) | 0.011±0.10 | -0.01±0.07 | 0.40 |
Values are expressed as means ± SD or median (IQR)
Funding
- NIDDK Support