Early changes in the urine-to-serum uric acid ratio are associated with subsequent eGFR slope during tolvaptan therapy in ADPKD

Background Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) through vasopressin V2 receptor blockade. We investigated whether the urine-to-serum (U/S) uric acid (UA) ratio, a simple, clinically accessible index, reflects early physiological changes after tolvaptan initiation and is associated with subsequent changes in renal function. Methods This single-center prospective observational study included 72 patients with ADPKD who initiated tolvaptan. Multivariable regression analyses evaluated factors associated with the initial change in the U/S UA ratio and its association with subsequent annual changes in estimated glomerular filtration rate (eGFR). Results The mean observation period was 2.6 ± 1.4 years. At 1 month, serum UA increased from 6.0 ± 1.4 to 6.3 ± 1.5 mg/dL, whereas the U/S UA ratio decreased from 4.3 ± 3.1 to 1.8 ± 1.2 (both P < 0.0001). Fractional excretion of UA did not change significantly, whereas urine osmolality decreased markedly. A larger initial decrease in the U/S UA ratio was associated with a slower subsequent annual eGFR decline. However, this association was attenuated and was no longer statistically significant after adjustment for the initial change in urine osmolality. In sex-stratified analyses, the association was significant in women but not in men, although the sex-by-U/S UA ratio change interaction was not significant (P = 0.883). Conclusions The U/S UA ratio is a simple, clinically accessible index reflecting early physiological changes after tolvaptan initiation. Its association with subsequent eGFR decline appears partly influenced by changes in urine osmolality and requires prospective validation.