Interactive association of serum uric acid and total bilirubin with renal dysfunction among community-dwelling subjects

Chronic kidney disease is a major public health concern. Serum uric acid (SUA) at high levels was oxidative stress agents, and total bilirubin (T-BiL) at mildly increased levels was potent antioxidants, but whether SUA and T-BiL produce an additive interaction for the risk of renal dysfunction remains unclear. The subjects comprised 567 men aged 71 +/- 8 (mean +/- standard deviation) years and 853 women aged 70 +/- 8 years from a rural village. We examined the relationship between SUA and T-BiL, and renal function was evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation. Stepwise multiple regression analysis using eGFR as an objective variable, adjusted for risk factors as explanatory variables, showed that SUA (beta = -0.358, p < 0.001) as well as age (beta = -0.534, p < 0.001), drinking status (beta = 0.119, p < 0.001), and the presence of antihypertensive medication (beta = -0.058, p = 0.005) were significantly and independently associated with eGFR, but T-BiL was not associated with eGFR. While in the group with the highest tertile of SUA, T-BiL (beta = 0.081, p = 0.032) was significantly and independently associated with eGFR, and in the group with the lowest to middle tertile of SUA, T-BiL was not associated with eGFR. In addition, interaction between SUA and T-BiL (F = 8.512, p = 0.004) as well as age, drinking status, the presence of antihypertensive medication, SUA, and T-BiL was a significant and independent determinant for eGFR. Our data demonstrated that low T-BiL could be important as a potential risk factor for renal dysfunction in those with high SUA.