The association of albuminuria with tubular reabsorption of uric acid: results from a general population cohort.

Background: Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption.

Methods And Results: Included were 7688 participants of the PREVEND Study, an observational, general population-based cohort study. Linear regression analyses were used to test associations of baseline albuminuria with baseline serum uric acid concentration and tubular uric acid reabsorption (calculated as [100-fractional uric acid excretion]%). Cox regression analyses were used to study the association of baseline serum uric acid and albuminuria with incident cardiovascular morbidity and mortality. In cross-sectional analyses, albuminuria was associated positively with serum uric acid concentration, both crude and after adjustment for potential confounders (both P<0.001). Albuminuria was found to be associated positively with tubular uric acid reabsorption, again both crude and after adjustment for potential confounders (both P<0.001). In longitudinal analyses during a median follow-up of 10.5 years, 702 cardiovascular events occurred. After adjusting for cardiovascular risk factors, both albuminuria and serum uric acid were associated with incident cardiovascular events (Hazard Ratios 1.09 [1.03 to 1.17], P=0.01 and 1.19 [1.09 to 1.30], P<0.001, respectively). A significant interaction between these variables was present (P<0.001), consistent with high serum uric acid being less predictive for cardiovascular morbidity and mortality in the presence of high albuminuria and vice versa.

Conclusions: Albuminuria is strongly associated with tubular uric acid reabsorption, and consequently with serum uric acid concentration. This phenomenon may explain in part why albuminuria is associated with cardiovascular outcome.