Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan.

Introduction: Although dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, delays the progression of chronic kidney disease (CKD), its effect on patients with autosomal dominant polycystic kidney disease (ADPKD) has not been established. We conducted an open-label, randomized controlled crossover trial to evaluate the additive effects of dapagliflozin in patients with ADPKD receiving tolvaptan.

Methods: A total of 27 patients were randomly counterbalanced to receive dapagliflozin 10 mg or usual care without dapagliflozin for 6 months. The primary endpoint was the slope of the estimated glomerular filtration rate (eGFR) determined by linear regression from 1 to 6 months, and the secondary endpoints included changes in total kidney volume (TKV). eGFR was calculated based on creatinine levels (eGFR), cystatin C levels (eGFR), and the mean of eGFR and eGFR (eGFR).

Results: There were significant attenuations in the eGFR and eGFR slopes during the dapagliflozin trial compared with the one without dapagliflozin (2.57 ± 7.88 vs. -5.65 ± 9.57 ml/min per 1.73 m per year,  = 0.002; 3.91 ± 11.40 vs. -8.43 ± 13.44 ml/min per 1.73 m per year,  = 0.003, respectively). Meanwhile, the eGFR slope was potentially moderate during the trial with dapagliflozin (1.03 ± 10.78 vs. -3.66 ± 8.88 ml/min per 1.73 m per year,  = 0.06). The 6-month change in TKV was significantly attenuated during the trial with dapagliflozin compared with the one without dapagliflozin (-0.44 ± 4.91% vs. 5.04 ± 8.09%,  = 0.01).

Conclusion: In patients with ADPKD treated with tolvaptan, dapagliflozin may have an additive effect in slowing ADPKD progression.