Hyperuricemia in Chronic Kidney Disease: Clinical Evidence and the Missing Role of Urinary Uric Acid Handling
Abstract
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.
Related
- Interactions between chronic kidney disease and hyperuricemia in children: mechanisms, clinical manifestations and management updates
- Gut Dysbiosis, Uremic Toxins, and NLRP3 Signaling in Chronic Kidney Disease: From Mechanistic Evidence to Clinical Biomarker Evaluation.
- Soluble guanylate cyclase modulation in heart failure and chronic kidney disease: mechanisms, clinical evidence, and translational boundaries
- Association of low physical performance assessed by five-time chair stand test with new-onset and severity of chronic kidney disease: hybrid evidence from public health and clinical settings
- Trajectories of body roundness index and risk of incident hyperuricemia in middle-aged and older Chinese adults: evidence from the China Health and Retirement Longitudinal Study
BibTeX
@article{takata2026hyperuricemia,
title = {{Hyperuricemia in Chronic Kidney Disease: Clinical Evidence and the Missing Role of Urinary Uric Acid Handling}},
author = {Tomoaki Takata and Ichiro Hisatome and Hajime Isomoto},
journal = {Internal Medicine},
year = {2026},
month = jul,
doi = {10.2169/internalmedicine.7918-26},
url = {https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7918-26/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Hyperuricemia in Chronic Kidney Disease: Clinical Evidence and the Missing Role of Urinary Uric Acid Handling
AU - Tomoaki Takata
AU - Ichiro Hisatome
AU - Hajime Isomoto
PY - 2026
DA - 2026/07/25
JO - Internal Medicine
DO - 10.2169/internalmedicine.7918-26
UR - https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7918-26/_article
AB - 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.
SN - 1349-7235
SN - 0918-2918
ER -