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.