Abstract: SA-PO748
The Effects of Allopurinol on Xanthine Oxidase Activity and Expression in CKD
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Lacina, Nicole Grace, The University of Iowa, Iowa City, Iowa, United States
- Scerbo, Diego, The University of Iowa, Iowa City, Iowa, United States
- Kruse, Nicholas, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
- Sun, Mingyao, The University of Iowa, Iowa City, Iowa, United States
- Taylor, Eric, The University of Iowa, Iowa City, Iowa, United States
- Jalal, Diana I., The University of Iowa, Iowa City, Iowa, United States
Background
Allopurinol lowers uric acid levels and may improve vascular function in chronic kidney disease (CKD). It is unclear whether the effects of allopurinol are mediated by xanthine oxidase (XO) inhibition, uric acid-lowering, or both. We hypothesized that allopurinol suppresses serum XO activity and reduces endothelial XO protein expression.
Methods
We anlayzed serum and endothelial cells samples from 45 CKD patients who participated in a randomized controlled trial of allopurinol vs placebo. Serum XO activity was determined and the expression of endothelial XO protein was evaluated (immunofluorescence). Serum xanthine levels were measured via mass spectrometry. Change from baseline was compared for both study groups.
Results
Baseline serum uric acid correlated with baseline CKD-EPI estimated GFR (r = 0.57, p value <0.0001) but not with serum XO activity (r =0.10, p value 0.52) or endothelial XO protein expression (r =0.2, p value=0.56). There was no correlation between serum XO activity or endothelial XO protein expression with baseline brachial artery flow-mediated dilation (BA-FMD) or CKD-EPI estimated GFR. As shown in the Table, allopurinol lowered serum uric acid levels and increased serum xanthine levels significantly. However, allopurinol did not decrease serum XO activity or the expression of endothelial XO protein. Change in XO activity and XO protein expression did not correlate with change in BA-FMD.
Conclusion
Our data suggest that allopurinol effectively lowers serum uric acid levels by inhibition of XO activity in the liver. However, contrary to our hypothesis, allopurinol does not significantly affect serum XO activity or XO protein expression in the endothelium. In addition our findings suggest that the main factor for increased serum uric acid in CKD is reduced kidney function.
Changes in serum uric acid, serum XO activity, and endothelial XO expression by study group
| Allopurinol (n=24) | Placebo(n=21) | P value | |
| Serum uric acid (mg/dL) | -3.7(1.0) | 0.14(1.46) | <0.0001 |
| Serum xanthine (RSI) | 2703(2037) | -4.7(177) | <0.0001 |
| Serum XO activity (mU/mL) | -0.21(0.56) | -0.13(0.34) | 0.68 |
| XO endothelial expression* | 0.08(0.34) | 0.22(0.41) | 0.55 |
RSI: relative signal intensity, *: arbitrary units, normalized to XO expression in human umbilical endothelial cells
Funding
- NIDDK Support