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 in 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 in 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.