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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.

SUBMITTER: Jalal DI

PROVIDER: S-EPMC5328166 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Vascular Function and Uric Acid-Lowering in Stage 3 CKD.

Jalal Diana I DI Decker Emily E Perrenoud Loni L Nowak Kristen L KL Bispham Nina N Mehta Tapan T Smits Gerard G You Zhiying Z Seals Douglas D Chonchol Michel M Johnson Richard J RJ

Journal of the American Society of Nephrology : JASN 20160912 3

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 functi ...[more]

PMID: 27620990

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Project description:Rationale & objectiveHyperuricemia is associated with chronic kidney disease (CKD) progression. We evaluated whether lowering serum uric acid levels improves levels of biomarkers of kidney damage.Study designPost hoc analysis of clinical trial participants.Setting & participantsA double-blind randomized placebo-controlled study designed to lower serum uric acid levels. 80 patients with stage 3 CKD and asymptomatic hyperuricemia were randomly assigned to allopurinol treatment or placebo (300 mg/d) for 12 weeks.Exposure/predictorAllopurinol treatment versus placebo.Outcomes & measuresWe evaluated the change from baseline for the following urinary biomarkers of kidney damage: albumin-creatinine ratio (ACR), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and transforming growth factor β1 (TGF-β1). Additionally, we evaluated CKD Epidemiology Collaboration (CKD-EPI)-estimated glomerular filtration rate (eGFR) and cystatin C eGFR.Analytical approachGeneralized linear mixed modeling was used.ResultsAfter 12 weeks, allopurinol (compared to placebo) significantly lowered serum uric acid levels with an estimate of -3.3 mg/dL (95% CI, -4.1 to -2.5 mg/dL; P < 0.001). Estimates for the change for allopurinol versus placebo over time were 1.09 (95% CI, 0.77-1.54) for ACR, 0.77 (95% CI, 0.36-1.63) for NGAL, and 2.36 (95% CI, 0.97-5.70) for TGF-β1. The model did not converge for KIM-1, but Wilcoxon signed rank test showed no significant difference in change from baseline between study groups. There was no significant change observed in CKD-EPI eGFR or cystatin C eGFR.LimitationsPost hoc analysis and short duration of the study.ConclusionsUric acid-lowering with allopurinol is not associated with improvement in levels of biomarkers of kidney damage in patients with asymptomatic hyperuricemia and stage 3 CKD.FundingThe study was funded by the National Institutes of Health through a career development award, K23DK088833, and the Clinical and Translational Science Award UL1TR002537.Trial registrationNCT01228903.

Project description:BackgroundThe present study was designed to determine the effect of short-term moderate-intensity exercise training on arterial stiffness in patients with chronic kidney disease (CKD) stage 3.Study designRandomized controlled trial with a parallel-group design.Setting & participantsTesting and training sessions were performed at Springfield College. 46 (treatment group, n=25; control group, n=21) patients with CKD with diabetes and/or hypertension completed the study.InterventionThe aerobic training program consisted of 16 weeks of supervised exercise training at 50%-60% peak oxygen uptake (Vo2peak) 3 times per week, while the control group remained sedentary. Identical testing procedures were performed following the 16-week intervention.OutcomesThe primary outcome was arterial stiffness. Secondary outcomes were aerobic capacity, various blood parameters (endothelin 1, nitrate/nitrite, and high-sensitivity C-reactive protein), and health-related quality of life.MeasurementsArterial stiffness was assessed with aortic pulse wave velocity (PWV), aerobic capacity by Vo2peak, blood parameters by enzyme-linked immunosorbent assays, and health-related quality of life by the 36-Item Short Form Health Survey (SF-36). Participants attended 4 sessions before being randomly assigned to either the treatment or control group. Participants gave consent during the first session, whereas a graded exercise test with measurement of Vo2peak was completed during the second session. During sessions 3 and 4, aortic PWV was measured at rest prior to 40 minutes of either moderate-intensity exercise training or seated rest. A venous blood sample was obtained prior to exercise or rest and participants completed the SF-36 questionnaire.Results16 weeks of training led to an 8.2% increase in Vo2peak for the treatment group (P=0.05), but no changes in aortic PWV .LimitationsRandomization was not concealed and was violated on one occasion; also, use of an indirect measurement of endothelial function and the short duration of the intervention.ConclusionsShort-term moderate-intensity exercise training does not alter arterial stiffness in patients with CKD, but seems to reduce endothelin 1 levels.

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Vascular Function and Uric Acid-Lowering in Stage 3 CKD.

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Vascular Function and Uric Acid-Lowering in Stage 3 CKD.

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