Title:Serum Uric Acid and Progression of Autosomal Dominant Polycystic Kidney Disease: Results from the HALT PKD Trials
Volume: 17
Issue: 3
Author(s): Godela M. Brosnahan*, Zhiying You, Wei Wang, Berenice Y. Gitomer and Michel Chonchol
Affiliation:
- University of Colorado Anschutz Medical Campus, Aurora, Colorado,United States
Keywords:
Autosomal dominant polycystic kidney disease, serum uric acid, total kidney volume, estimated glomerular filtration
rate, HALT PKD trials, chronic kidney disease.
Abstract:
Background: Epidemiological studies have suggested that elevated serum uric acid may
contribute to the progression of chronic kidney disease. However, no large prospective study has
examined whether hyperuricemia is an independent risk factor for the progression of autosomal
dominant polycystic kidney disease (ADPKD).
Methods: We measured uric acid in stored serum samples from the 2-year study visit of 671 participants
from the HALT PKD multicenter trials. Participants were categorized according to uric acid
tertiles. For Study A (participants aged 15-49 years with preserved kidney function, n=350), we
used linear mixed effects models to examine the association between uric acid and repeated measures
of height-adjusted total kidney volume (htTKV), the primary outcome for Study A. For
Study B (participants aged 18-64 with decreased kidney function, n=321), we used Cox proportional
hazards models to assess the hazard for the combined endpoint of 50% loss in estimated glomerular
filtration rate (eGFR), end-stage kidney disease (ESKD), or death, the primary outcome for
Study B. To assess the association of uric acid with the slope of eGFR decline (secondary outcome
of HALT A and B), we used linear mixed effects models for the combined population of Study A
and B.
Results: In the unadjusted model, the annual change in htTKV was 2.7% higher in the highest uric
acid tertile compared to the lowest (p<0.001), but this difference became insignificant after adjustment
for gender. Men had faster TKV growth than women (p<0.001). There was no difference in
eGFR decline between the 3 uric acid tertiles. Hazard ratios for the clinical endpoint were 2.9 (95%
confidence interval, 1.9-4.4) and 1.8 (1.1-2.8) respectively in the high and medium uric acid groups
in unadjusted and partially adjusted models (p<0.001), but the significance was lost after adjustment
for baseline eGFR. Results were similar when uric acid was examined as a continuous variable.
Conclusion: Elevated serum uric acid is not an independent risk factor for disease progression in
ADPKD.
