ADPKD Therapy options:

State-of-the-Art Pharmacotherapy

• Focus Shift: Towards pharmacological interventions with disease-modifying effects.
• Central Role: Intracellular cAMP levels in cystogenesis and cyst expansion.

V2 Receptor Blockade

• Vasopressin Role: Induces cAMP generation and drives cyst expansion.
• Tolvaptan: V2 receptor inhibitor; reduces kidney growth rate and attenuates eGFR loss.
• Clinical Trials: TEMPO 3:4, TEMPO 4:4, REPRISE trials support tolvaptan's effectiveness.

Somatostatin Analogues

• Somatostatin Signaling: Reduces cAMP levels; potential in rodent models.
• Trials: Phase 2 and 3 trials exploring somatostatin analogues.

Repurposing Drugs

• Promising Strategy: Drugs with established safety profiles for other indications.
• Evaluated Drugs: Statins, metformin, mTOR inhibitors.
• Current Status: Lovastatin and metformin show benefits; mTOR inhibitors not conclusive.
• Ongoing Exploration: Tyrosine kinase inhibitors and targeted therapies.

Conclusion

• ADPKD Management Advances: Breakthroughs in molecular pathogenesis and drug interventions.
• Tolvaptan: First approved disease-modifying therapy, offering benefits in kidney growth and function preservation.
• Future Prospects: Repurposing drugs and potential combination therapies in ongoing clinical trials continue to enhance understanding.