Renal hypouricemia is associated with a decreased glomerular filtration rate, but not with cardiovascular events or all-cause mortality: the Shizuoka Study

Background: Renal hypouricemia is a rare inherited disorder characterized by increased uric acid excretion, causing abnormally low serum uric acid levels.Its long-term effects on cardiovascular disease (CVD) incidence, all-cause mortality, and renal function remain unclear.Methods: We included 450,204 participants (mean age, 66.3 10.5 years; 37.2% male).The baseline was defined as the earliest date of participation in specific health checkups conducted between 2013 and 2022.Clinical laboratory values, comorbidities, and uric acid-lowering medication use were obtained from the Shizuoka Kokuho Database.Results: Over a mean follow-up of 6.1 years, 10,951 incident CVD cases and 29,988 deaths were recorded.Patients in the renal hypouricemia group were younger with a slightly higher estimated glomerular filtration rate (eGFR) at baseline than those in the control group.Multiple linear regression analysis revealed that hypouricemia was significantly associated with lower baseline eGFR ( = -0.034,p < 0.001).The longitudinal analysis revealed that hypouricemia was associated with an increased risk of rapid renal function decline, defined as an eGFR slope decline of 3 mL/min/1.73m 2 per year (adjusted odds ratio, 1.59; 95% confidence interval [95% CI], 1.08-2.28;p = 0.019).Hypouricemia was not associated with CVD incidence or all-cause mortality (hazard ratio [HR], 0.74; 95% CI, 0.39-1.43;p = 0.373 and HR, 1.25; 95% CI, 0.90-1.73;p = 0.181) in Cox proportional hazards models.Conclusion: Although renal hypouricemia was not associated with an increased CVD or all-cause mortality risk, it may be linked to a higher risk of rapid renal function decline.