The impact of elevation of serum uric acid level on the natural history of glomerular filtration rate (GFR) and its sex difference

Background. The impact of elevation of the serum uric acid level (SUA) on the natural history of glomerular filtration rate (GFR) remains controversial. Methods. If elevation of SUA is a result, rather than a cause, of a decline in GFR, the relationship between SUA and GFR should be the same in the same population over years except for shifts by age-dependent reduction of GFR. We tested this hypothesis using data from two cohorts and a group of allopurinol-treated patients. Results. In Cohort 1 consisting of urban residents aged 40.6 +/- 9.0 years (n = 3 446), SUA was inversely correlated with estimated GFR (eGFR) in both men and women, and the slope of the SUA-eGFR relationship was steeper in women than in men. The slopes of the regression lines became significantly steeper after a 6-year interval in both sexes, and the change in the slope was larger in women. A similar sex difference in the SUA-eGFR relationship and 6-year change in the slope were observed in Cohort 2 consisting of rural town residents aged 61.7 +/- 12.2 years (n = 404). Multiple regression analyses showed that explanatory factors of eGFR after a 6-year interval were age and SUA at baseline in both cohorts, and partial regression coefficients of SUA were more negative in women than in men. The SUA-eGFR relationship in allopurinol-treated patients (n = 346, 63.5 +/- 13.3 years old) was similar to that in Cohort 2. Conclusions. The results indicate that elevation of SUA accelerates the yearly decline in eGFR and that women are more susceptible to urate-induced decline in eGFR.