Serum Uric Acid in Chronic Kidney Disease as a Marker of Risk or a Modifiable Driver of Progression: A Systematic...

Serum uric acid has been investigated as a marker and potential therapeutic target in chronic kidney disease (CKD), but its clinical significance remains uncertain because hyperuricemia may represent both a consequence of impaired renal clearance and a possible contributor to kidney injury. This systematic review evaluated associations between serum uric acid status, urate-lowering interventions, and renal outcomes in adults with CKD or hyperuricemia-associated kidney disease. PubMed/MEDLINE, Scopus, and Web of Science were searched for studies published from January 1, 2019, to April 1, 2026, with supplementary citation searching conducted during revision. Seven studies met the eligibility criteria, including randomized controlled trials, trial sub-analyses, exploratory analyses, and post-hoc analyses. Narrative synthesis was performed because clinical and methodological heterogeneity precluded meta-analysis. Higher baseline or sustained serum uric acid was associated with less favorable renal trajectories in selected populations, particularly when assessed longitudinally or as average exposure during follow-up. However, pharmacologic urate reduction did not consistently improve albuminuria, proteinuria, measured glomerular filtration rate, or estimated glomerular filtration rate outcomes. In Preventing Early Renal Loss in Diabetes (PERL), the between-group difference in measured glomerular filtration rate with allopurinol versus placebo was 0.001 mL/min/1.73 m² (95% confidence interval: -1.9 to 1.9; p=0.99). In the Controlled Trial of Slowing of Kidney Disease Progression from the Inhibition of Xanthine Oxidase (CKD-FIX), the corresponding difference in annual estimated glomerular filtration rate decline was -0.10 mL/min/1.73 m² (95% confidence interval: -1.18 to 0.97; p=0.85). These findings support serum uric acid as a context-dependent renal risk signal but do not justify urate-lowering therapy solely for universal renoprotection. Future studies should prioritize serial urate assessment, phenotype-specific analyses, earlier disease stages, intracellular urate biology, and hard kidney outcomes to determine when uric acid represents a marker, mediator, or genuinely modifiable target in CKD progression. The objective of this systematic review was to evaluate the relationship between serum uric acid status, urate-lowering interventions, and renal outcomes in adults with CKD or hyperuricemia-associated kidney disease. Specifically, this review aimed to synthesize evidence on whether baseline, longitudinal, or average serum uric acid levels and pharmacologic urate reduction are associated with CKD progression, estimated glomerular filtration rate (eGFR) decline, albuminuria, proteinuria, or kidney failure-related outcomes. By integrating prognostic and interventional evidence, this review seeks to clarify whether serum uric acid should be understood primarily as a renal risk marker, a potential disease mediator, a modifiable therapeutic target, or a context-dependent combination of these roles.