Vascular Function and Uric Acid-Lowering in Stage 3 CKD

• Published in: Journal of the American Society of Nephrology Vol. 28; no. 3; pp. 943 - 952
• Main Authors: Jalal, Diana I, Decker, Emily, Perrenoud, Loni, Nowak, Kristen L, Bispham, Nina, Mehta, Tapan, Smits, Gerard, You, Zhiying, Seals, Douglas, Chonchol, Michel, Johnson, Richard J
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01-03-2017
• Subjects: Allopurinol - pharmacology; Allopurinol - therapeutic use; Clinical Research; Double-Blind Method; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Humans; Hyperuricemia - etiology; Hyperuricemia - prevention & control; Male; Middle Aged; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - physiopathology; Severity of Illness Index; flow-mediated dilation; allopurinol; CKD; uric acid
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2016050521

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 (
=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.