Abstract: TH-PO478

Uric Acid-Lowering and Markers of CKD-Associated Mineral and Bone Disorder, Vascular Calcification, and Atherosclerosis

Session Information

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)
VariablePlacebo
(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±0.480.45
Phosphorus (mg/dL)-0.13±0.650.08±0.660.46
25 vitamin D (ng/mL)2.41±6.150.29±5.130.46
1,25 vitamin D (pg/mL)0.94±8.71-1.53±9.980.63
24,25 vitamin D (pg/mL)0.15±0.79-0.14±0.740.42
iPTH (pg/mL)1.99±31.812.27±29.280.77
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±57.80.42
CIMT (mm)0.011±0.10-0.01±0.070.40

Values are expressed as means ± SD or median (IQR)

Funding

  • NIDDK Support