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

doi:10.1016/j.xkme.2019.11.007

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

Kidney Med. 2020 Feb 26;2(2):155-161. doi: 10.1016/j.xkme.2019.11.007. eCollection 2020 Mar-Apr.

Authors

Loni Perrenoud¹, Nicholas T Kruse², Emily Andrews¹, Zhiying You¹, Michel Chonchol¹, Chaorong Wu³, Patrick Ten Eyck³, Diana Zepeda-Orozco⁴, Diana Jalal²

Affiliations

¹ Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
² Division of Nephrology, Department of Internal Medicine, Carver College of Medicine, Iowa City, IA.
³ Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA.
⁴ Division of Pediatric Nephrology, Dialysis and Transplantation, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA.

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.

Associated data

ClinicalTrials.gov/NCT01228903

Abstract

Associated data

Grants and funding