Why Dapagliflozin is Not Recommended for ADPKD
Dapagliflozin is explicitly not recommended for chronic kidney disease in patients with polycystic kidney disease because it is not expected to be effective in this population and may accelerate kidney cyst growth. 1
FDA Label Contraindication
The FDA-approved prescribing information for dapagliflozin specifically states: "DAPAGLIFLOZIN TABLETS are not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease... DAPAGLIFLOZIN TABLETS are not expected to be effective in these [patients]." 1 This represents the highest level of regulatory guidance against its use in ADPKD.
Current Guideline Position
The 2025 KDIGO ADPKD guidelines recommend not using sodium-glucose cotransporter-2 inhibitors to slow the rate of eGFR decline in ADPKD, until further research determines their efficacy and safety. 2 This conservative stance reflects insufficient evidence of benefit and potential for harm in this specific population.
Evidence of Harm: Accelerated Kidney Growth
Multiple case reports and small series demonstrate concerning effects of dapagliflozin in ADPKD patients:
A 38-year-old woman experienced dramatic kidney enlargement from 1,641 mL to 2,297 mL over 340 days of dapagliflozin treatment, with eGFR declining from 67.3 to 51.4 mL/min/1.73 m². After discontinuation, both TKV and eGFR slightly improved. 3
In a retrospective series of 20 ADPKD patients, short-term dapagliflozin (102 ± 20 days) significantly increased height-adjusted TKV from 599 to 617 mL/m (p = 0.002) while eGFR decreased from 47.9 to 40.8 mL/min/1.73 m² (p < 0.001). 4
A retrospective study of seven patients showed that all patients experienced increased annual height-corrected total kidney volume during dapagliflozin treatment. 5
Mechanistic Concerns
The pathophysiologic rationale for avoiding dapagliflozin in ADPKD includes:
Increased intratubular urinary osmotic pressure from glycosuria may promote cyst expansion. 3
Compensatory glucose reabsorption by SGLT1 in the late proximal tubule may occur, potentially worsening tubular workload. 3
Increased vasopressin secretion due to the diuretic effect of SGLT2 inhibitors is particularly problematic in ADPKD, where vasopressin is a primary driver of cyst growth and disease progression. 3, 6
Hypertrophy of collecting duct cells caused by elevated vasopressin may be exacerbated. 3
Conflicting Evidence Requires Caution
While some small case series suggest potential eGFR slope improvement when dapagliflozin is combined with tolvaptan and RAS inhibitors 7, 5, 6, these reports consistently show continued or accelerated kidney volume growth despite any eGFR benefits. 7, 5 Given that total kidney volume is a validated surrogate endpoint for ADPKD progression, this finding is deeply concerning.
The most recent and highest-quality evidence—the FDA drug label and 2025 KDIGO guidelines—both recommend against dapagliflozin use in ADPKD. 1, 2 The small case series suggesting benefit are retrospective, uncontrolled, and show conflicting results on the critical outcome of kidney volume.
Common Pitfalls to Avoid
Do not extrapolate DAPA-CKD trial results to ADPKD patients. ADPKD was an explicit exclusion criterion in this landmark trial, and the disease pathophysiology differs fundamentally from other causes of CKD. 5
Do not assume combination with tolvaptan mitigates risk. Even when combined with the vasopressin V2 receptor antagonist tolvaptan, dapagliflozin still increased kidney volume in multiple reports. 7, 5
Do not use dapagliflozin for cardiovascular or diabetic indications without considering ADPKD-specific risks. While dapagliflozin has proven cardiovascular and renal benefits in other populations 2, these benefits have not been demonstrated in ADPKD and may be outweighed by accelerated cyst growth.
Alternative Approaches
For ADPKD patients requiring renal protection:
Tolvaptan remains the only FDA-approved disease-modifying therapy that slows eGFR decline by approximately 1.3 mL/min/1.73 m² per year and reduces total kidney volume growth by 2.7% versus placebo. 2, 8
Strict blood pressure control with ACE inhibitors or ARBs as first-line agents is recommended. 2
High water intake (2-3 liters daily) to suppress vasopressin is suggested for patients with eGFR ≥30 mL/min/1.73 m². 2