ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

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