Table 1.

Proposed roadmap to establish the safety and efficacy of SGLT2i for kidney and cardiovascular disease in persons with ADPKD

(A) Preclinical1. Explore the efficacy and safety of SGLT2i in preclinical models of ADPKD that more closely resemble the kidney conditions: i.e. defective Pkd1 gene and long natural history/and long-term SGLT2i treatment, leading to severe kidney disease well into adulthood.2. Detailed characterization of the impact of SGLT2i on vasopressin and vasopressin signaling under nondiabetic conditions.(B) Clinical. These sequential steps are proposed:1. Create an SGLT2i-ADPKD task force.2. Contact the leadership of all phase 3, large scale trials of cardiovascular safety or cardiovascular outcomes to extract, pool and analyze the safety and outcomes of persons with ADPKD that may have been enrolled in these trials.3. Create a registry of ADPKD patients treated with SGLT2i for diabetes or cardiovascular conditions, assessing safety (urinary tract infections, copeptin, eGFR trajectories, TKV and albuminuria) as well as kidney efficacy (eGFR trajectories, TKV and albuminuria) outcomes.4. Design short-term exploratory trials addressing the acute and short-term impact of SGLT2i on vasopressin, vasopressin signaling, eGFR and TKV, as well as safety.5. Based on the result for steps 2 through 4, decide on the need, feasibility and design of larger, long-term phase 2 and phase 3 trials with endpoint efficacy on kidney protection or add warnings to drug labels regarding potential risks in ADPKD patients.