U-shaped relationship between serum uric acid levels and intrarenal hemodynamic parameters in healthy subjects

Hyperuricemia has been reported to affect renal hemodynamics. In a recent study, both low and high levels of serum uric acid (SUA) were found to be associated with loss of kidney function. The goal of this study was to evaluate the relationship between SUA levels and intrarenal hemodynamic parameters in healthy subjects, using plasma clearance of para-aminohippurate (C_PAH) and inulin (C_in). Renal and glomerular hemodynamics were evaluated by simultaneous measurements of C_PAH and C_in in 48 healthy subjects (54.6 ± 13.4 yr). Intrarenal hemodynamic parameters, including efferent and afferent (R_a) arteriolar resistance, were calculated using Gómez's formulas. Relationships of SUA levels with these intrarenal hemodynamic parameters were examined. In quadratic regression analysis, SUA levels had a significant inverse U-shaped relationship with C_in (P < 0.0001, R² = 0.350) and C_PAH (P = 0.0093, R² = 0.188) and a U-shaped relationship with R_a (P = 0.0011, R² = 0.262). In multiple regression analysis with normal (3.5-6.0 mg/dl) and mildly low or high (<3.5 or >6.0 mg/dl) SUA levels entered as dummy variables of zero and one, respectively, mildly low or high SUA levels were significantly and independently associated with R_a (β = 0.230, P = 0.0403) after adjustment for several factors (R² = 0.597, P < 0.0001). Both mild hyperuricemia and mild hypouricemia are significantly associated with increased R_a, although weakly. The increase in R_a in subjects with mild hyperuricemia or hypouricemia may be related to renal hemodynamic abnormalities, possibly leading to a decline in renal function.