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.