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 (β = -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/1.73 m2 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.