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Randomized Controlled Trial
. 2017 Mar;28(3):943-952.
doi: 10.1681/ASN.2016050521. Epub 2016 Sep 12.

Vascular Function and Uric Acid-Lowering in Stage 3 CKD

Diana I Jalal  1   2 , Emily Decker  1 , Loni Perrenoud  1 , Kristen L Nowak  1 , Nina Bispham  3 , Tapan Mehta  1 , Gerard Smits  1 , Zhiying You  1 , Douglas Seals  3 , Michel Chonchol  1 , Richard J Johnson  1
Affiliations
Randomized Controlled Trial

Vascular Function and Uric Acid-Lowering in Stage 3 CKD

Diana I Jalal et al. J Am Soc Nephrol. 2017 Mar.

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.

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Figures

Figure 1.
Figure 1.
Out of 80 randomized subjects, 70 completed the study. Study schema. MDRD, Modification of Diet in Renal Disease.
Figure 2.
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).
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References

    1. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS: Prevalence of chronic kidney disease in the United States. JAMA 298: 2038–2047, 2007 - PubMed
    1. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH: Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 164: 659–663, 2004 - PubMed
    1. Brantsma AH, Bakker SJ, Hillege HL, de Zeeuw D, de Jong PE, Gansevoort RT; PREVEND Study Group : Cardiovascular and renal outcome in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion. Nephrol Dial Transplant 23: 3851–3858, 2008 - PubMed
    1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351: 1296–1305, 2004 - PubMed
    1. McCullough PA, Jurkovitz CT, Pergola PE, McGill JB, Brown WW, Collins AJ, Chen SC, Li S, Singh A, Norris KC, Klag MJ, Bakris GL; KEEP Investigators : Independent components of chronic kidney disease as a cardiovascular risk state: results from the Kidney Early Evaluation Program (KEEP). Arch Intern Med 167: 1122–1129, 2007 - PubMed

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