Vascular Function and Uric Acid-Lowering in Stage 3 CKD

Abstract

Hyperuricemia may contribute to endothelial dysfunction in CKD. We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia (≥7 mg/dl in men and ≥6 mg/dl in women) randomized in a double-blinded manner to receive placebo or allopurinol for 12 weeks. Randomization was stratified according to presence or absence of diabetes mellitus. We measured vascular endothelial function by brachial artery flow-mediated dilation. No significant differences existed between groups at baseline; 61% of the participants had diabetes mellitus in both groups. The placebo and the allopurinol groups had baseline serum uric acid levels (SDs) of 8.7 (1.6) mg/dl and 8.3 (1.4) mg/dl, respectively, and baseline flow-mediated dilation values (SDs) of 6.0% (5.0%) and 4.8% (5.0%), respectively. Compared with placebo, allopurinol lowered serum uric acid significantly but did not improve endothelial function. In participants without diabetes mellitus, allopurinol associated with a trend toward improved flow-mediated dilation (+1.4% [3.9%] versus -0.7% [4.1%] with placebo), but this was not statistically significant (P=0.26). Furthermore, we did not detect significant differences between groups in BP or serum levels of markers of inflammation and oxidative stress. In conclusion, allopurinol effectively and safely lowered serum uric acid levels in adults with stage 3 CKD and asymptomatic hyperuricemia but did not improve endothelial function in this sample of patients.

Keywords: CKD; allopurinol; flow-mediated dilation; uric acid.

Copyright © 2017 by the American Society of Nephrology.

Figures

Figure 1.

Out of 80 randomized subjects, 70 completed the study. Study schema. MDRD, Modification of Diet in Renal Disease.

Figure 2.

Allopurinol did not significantly reduce the expression of NF-ҡB, NADPH oxidase, nitrotyrosine, or manganese superoxide dismutase (MnSOD) in the endothelial cells collected from study participants. The figures represent change in the expression of each protein from baseline by study group. Values for each sample were reported as arbitrary units and represent ratios of endothelial cell protein expression to human umbilical vein endothelial cell expression in order to account for any variation in the staining procedure. (A) NF-ҡB (n=32); (B) NADPH oxidase (n=32); (C) nitrotyrosine (n=30); (D) MnSOD (n=34).