Serum Uric Acid and Progression of Kidney Disease: A Longitudinal Analysis and Mini-Review

BACKGROUND: Increasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD); however, there are conflicting data regarding the role of hyperuricemia in the progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA) level and CKD progression in a Chinese population lived in Taiwan. METHODS: Patients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were identified in the electronic medical records (EMR) of a tertiary medical center and were followed up until December 31, 2011. Patients were divided into four UA categories at the cut-off 6, 8, and 10 mg/dL. CKD progression was estimated by the change of estimated glomerular filtration rate (eGFR) in the linear mixed models. Kidney failure was defined as an eGFR less than 15 mL/min/1.73 m(2) or requiring renal replacement therapy. RESULTS: A total of 739 patients were analyzed. In the full-adjusted model, patients with a baseline UA level ≥6 mg/dL had greater decline in eGFR ((β = -9.6, 95% CI -16.1, -3.1), comparing to those with a UA level less than 6 mg/dL. When stratifying patients into four UA categories, all three hyperuricemia categories (UA6-8, 8–10, ≥10 mg/dL) associated with a greater decline in eGFR over the follow-up period with an increasing dose-response, comparing to the lowest UA category. The risk of progression to renal failure increased 7% (hazard ratio 1.07, 95% CI 1.00, 1.14) for each 1mg/dL increase in baseline UA level. The influences of hyperuricemia on eGFR decline and the risk of kidney failure were more prominent in patients without proteinuria than those with proteinuria. CONCLUSION: Our study showed a higher uric acid level is associated with a significant rapid decline in eGFR and a higher risk of kidney failure, particularly in patients without proteinuria. Our findings suggest hyperuricemia is a potential modifiable factor of CKD progression.