Renoprotective effects of combination therapy with tolvaptan and dapagliflozin in autosomal dominant polycystic kidney disease: a four-case series

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), the most prevalent inherited kidney disorder, progresses inexorably to end-stage kidney disease (ESKD) with the vasopressin V2-receptor antagonist tolvaptan serving as a primary treatment option since 2014. While dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, was approved for treating chronic kidney disease in August 2021, its renoprotective effects in ADPKD remain uncertain due to potential vasopressin stimulation. We evaluated four Japanese ADPKD patients receiving combination therapy with tolvaptan and dapagliflozin for over two years. A 74-year-old woman (Mayo Class 1D, CKD stage 4) showed improved estimated glomerular filtration rate (eGFR) decline from - 1.39 to - 0.66 mL/min/1.73 m²/year. A 62-year-old woman (Mayo Class 1B, CKD stage 3b) demonstrated eGFR decline improvement from - 1.02 to - 0.66 mL/min/1.73 m²/year. A 39-year-old man (Mayo Class 1C, CKD stage 3a) exhibited significant improvement from - 5.00 to - 1.35 mL/min/1.73 m²/year. A 45-year-old woman (Mayo Class 1D, CKD stage 3b) showed marked improvement from - 14.12 to - 0.22 mL/min/1.73 m²/year. While eGFR decline decelerated in the control group, the combination therapy group showed more pronounced improvements. Height-adjusted total kidney volume (htTKV) in the group combination therapy showed variable responses: two patients experienced volume increases (+ 4.03%, + 3.65%/year), while two showed decreases (- 0.45%, - 3.65%/year). These cases suggest potential renoprotective benefits from combining tolvaptan and dapagliflozin in ADPKD patients. Careful monitoring of renal cyst enlargement is warranted with concurrent dapagliflozin use. Further research is needed to confirm these preliminary findings and establish optimal patient selection criteria for combination therapy.

Keywords: Autosomal dominant polycystic kidney disease; Estimated glomerular filtration rate decline; Height-adjusted total kidney volume; Sodium-glucose cotransporter-2 inhibitor; Vasopressin V2-Receptor antagonist.

Fig. 1

The progression in eGFR pre- and post- administration of tolvaptan, and post- administration of dapagliflozin (in the dapagliflozin group). eGFR estimated glomerular filtration rate, Dis discontinuation

Fig. 2

The progression in eGFR pre- and post- administration of tolvaptan and the period from December 2021 to April 2024 (in the control group). eGFR estimated glomerular filtration rate

Fig. 3

The progression of height adjusted TKV in the dapagliflozin group

Fig. 4

The progression of height adjusted TKV in the control group