Differential associations of transient hyperuricemia and transient hypouricemia with annual changes in estimated glomerular filtration rate in healthy participants: an observational study

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Abstract
Background: Dysuricemia, encompassing both hyperuricemia (serum uric acid: SUA > 7 mg/dl) and hypouricemia (SUA ≤ 3 mg/dL), has been linked to cardio-renal risks, but it remains unclear whether consistent or transient dysuricemia contributes to the risk of chronic kidney disease (CKD). Purpose: To investigate whether consistent and transient dysuricemia influences annual changes in the estimated glomerular filtration rate (eGFR) in healthy participants. Methods: We retrospectively analyzed 1142 healthy participants who underwent health checkups with at least four consecutive annual measurements of eGFR and SUA. Participants with consistently hyperuricemia, hypouricemia, or normouricemia (7 mg/dL ≥ SUA > 3 mg/dL) throughout follow-up were categorized as consistent hyperuricemia ( n = 36), consistent hypouricemia ( n = 8) and normouricemia ( n = 759), respectively. Others were classified as transient hyperuricemia ( n = 282) and transient hypouricemia ( n = 57). Annualized eGFR decline was compared using ANOVA, and incident CKD stage 3 events were evaluated using χ² or Fisher’s exact tests. Multivariable analyses were performed to examine the association between baseline SUA and subsequent renal outcomes. Results: Hyperuricemia was positively associated with obesity, liver dysfunction, dyslipidemia, and higher baseline eGFR compared with normouricemia, whereas hypouricemia showed negative associations with obesity and liver dysfunction. Transient hyperuricemia was significantly associated with obesity, liver dysfunction, and dyslipidemia relative to consistent normouricemia, while transient hypouricemia was negatively associated with obesity and liver dysfunction. Transient hyperuricemia exhibited significantly faster annual eGFR decline than normouricemia, while transient hypouricemia showed no significant difference. Baseline SUA ≥ 7 mg/dL was associated with higher baseline eGFR but predicted a significantly faster subsequent eGFR decline. In multivariable linear regression, baseline SUA level was independently associated with eGFR change, whereas baseline SUA status did not independently predict incident CKD stage 3. Conclusion: Transient hyperuricemia, rather than transient hypouricemia, is associated with accelerated eGFR decline in healthy individuals. Baseline SUA provides prognostic information regarding renal function trajectory, but does not independently predict CKD stage 3, suggesting that SUA should be interpreted as a clinically useful marker of renal vulnerability rather than a proven causal factor.

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