Uric Acid Lowering and Biomarkers of Kidney Damage in CKD Stage 3: A Post Hoc Analysis of a Randomized Clinical Trial

Loni Perrenoud, Nicholas T Kruse, Emily Andrews, Zhiying You, Michel Chonchol, Chaorong Wu, Patrick Ten Eyck, Diana Zepeda-Orozco, Diana Jalal, Loni Perrenoud, Nicholas T Kruse, Emily Andrews, Zhiying You, Michel Chonchol, Chaorong Wu, Patrick Ten Eyck, Diana Zepeda-Orozco, Diana Jalal

Abstract

Rationale & objective: Hyperuricemia is associated with chronic kidney disease (CKD) progression. We evaluated whether lowering serum uric acid levels improves levels of biomarkers of kidney damage.

Study design: Post hoc analysis of clinical trial participants.

Setting & participants: A 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/predictor: Allopurinol treatment versus placebo.

Outcomes & measures: We 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 approach: Generalized linear mixed modeling was used.

Results: After 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.

Limitations: Post hoc analysis and short duration of the study.

Conclusions: Uric 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.

Funding: The study was funded by the National Institutes of Health through a career development award, K23DK088833, and the Clinical and Translational Science Award UL1TR002537.

Trial registration: NCT01228903.

Keywords: Chronic kidney disease; allopurinol; kidney damage; kidney function; uric acid.

© 2020 The Authors.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Baseline and end-of-study values for urinary (A) albumin-creatinine ratio (ACR), (B) neutrophil gelatinase-associated lipocalin (NGAL), (C) kidney injury molecule 1 (KIM-1), and (D) transforming growth factor β1 (TGF-β1) according to treatment group. There was no difference in baseline values for any of the biomarkers of kidney damage between the allopurinol and placebo groups.

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Source: PubMed

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