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.