Hyperuricemia in Chronic Kidney Disease: Clinical Evidence and the Missing Role of Urinary Uric Acid Handling

Hyperuricemia is common in chronic kidney disease (CKD); however, its role in CKD progression remains unclear. A reduced kidney function elevates serum uric acid levels through impaired urinary excretion, while uric acid may injure the kidney. Although early studies suggested renoprotection from urate-lowering therapy (ULT), large randomized trials have not consistently shown that lowering serum uric acid levels slows the progression of CKD. One reason may be that the measurement of serum uric acid alone cannot distinguish between the underlying mechanisms, such as overproduction, reduced glomerular filtration, enhanced tubular reabsorption, or reduced extrarenal excretion. Urinary indices, such as the fractional excretion of uric acid and the urinary uric acid-to-creatinine ratio, provide complementary information on intrarenal urate handling, and approaches that integrate glomerular filtration and tubular reabsorption may support phenotype-based risk stratification. Although current evidence does not support uniform ULT for kidney protection, urinary urate indices may help characterize mechanism-specific phenotypes and guide the mechanism-matched selection of ULT.