SGLT2 inhibitors in autosomal dominant polycystic kidney disease: rationale, evidence gaps, and ongoing clinical trials.

Autosomal dominant polycystic kidney disease (ADPKD) remains the leading inherited cause of chronic kidney disease (CKD), with specific management largely relying on the approval of the selective vasopressin V2 receptor antagonist, tolvaptan, in recent years. However, the administration of tolvaptan is associated with several potential risks, including aquaretic side effects, dehydration, and acute kidney and liver injuries, highlighting the need for careful consideration of the optimal dosage. In this context, there has been increasing interest in the use of SGLT2 inhibitors for both diabetic and non-diabetic chronic kidney disease given their cardio- and nephroprotective roles, as well as their potential to delay progression to end-stage renal disease. Nevertheless, the exclusion of ADPKD patients from randomized controlled trials (RCTs) involving CKD patients receiving SGLT2 inhibitors-due to concerns about eGFR decline, cyst growth, and increased total kidney volume-has created a gap in evidence and uncertainty. Available observational studies indicate both beneficial and adverse effects, while ongoing trials aim to provide more definitive evidence on the safety and efficacy of SGLT2 inhibitors in this inherited CKD population. Therefore, this review aims to focus on the current treatment options for ADPKD patients and the promising role of SGLT2 inhibitors, drawing on the available literature and ongoing RCTs.