Journal article
Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial
PloS one, Vol.13(10), pp.e0205831-e0205831
2018
DOI: 10.1371/journal.pone.0205831
PMCID: PMC6200237
PMID: 30356327
Abstract
Background
Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD.
Methods
This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants.
Findings
Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase.
Conclusion
These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.
Details
- Title: Subtitle
- Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial
- Creators
- Emily S Andrews - Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of AmericaLoni Perrenoud - Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of AmericaKristen L Nowak - Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of AmericaZhiying You - Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of AmericaAndreas Pasch - Department of Biomedical Research, University of Bern, Bern, SwitzerlandMichel Chonchol - Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of AmericaJessica Kendrick - Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of AmericaDiana Jalal - Nephrology Division, The University of Iowa, Iowa City, IA, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.13(10), pp.e0205831-e0205831
- DOI
- 10.1371/journal.pone.0205831
- PMID
- 30356327
- PMCID
- PMC6200237
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Grant note
- K23 DK088833 / NIDDK NIH HHS R01 HL132868 / NHLBI NIH HHS
- Language
- English
- Date published
- 2018
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094311302771
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