Autosomal dominant polycystic kidney disease: new insights into treatment

Area of Science:

• Nephrology
• Genetics
• Pharmacology

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited kidney disorder globally.
• Recent research has deepened the understanding of ADPKD's molecular and cellular mechanisms.
• Current treatments primarily focus on hypertension management via renin-angiotensin-aldosterone system (RAAS) blockade.

Purpose of the Study:

• To review and highlight emerging and promising therapeutic strategies for ADPKD.
• To discuss the clinical implications and practical application of these new treatments for patients and healthcare providers.
• To emphasize the urgent need for novel ADPKD-targeted therapies compared to other renal diseases.

Main Methods:

• Literature review of recent animal and human studies on ADPKD pathology and treatment.
• Analysis of ongoing clinical trials for ADPKD therapies.
• Focus on therapies beyond mTOR inhibitors, including RAAS dual inhibition, vasopressin antagonists, increased fluid intake, and cyclic adenosine monophosphate receptor blockade.

Main Results:

• Dual RAAS inhibition, vasopressin receptor antagonists, and increased fluid intake show promise as ADPKD treatments.
• Blockade of specific cyclic adenosine monophosphate receptors is also under investigation.
• Mammalian target of rapamycin (mTOR) inhibitor therapy has not proven effective for ADPKD.

Conclusions:

• Several novel therapeutic avenues are emerging for ADPKD, offering potential improvements over current standards of care.
• These advancements require careful consideration for immediate clinical practice integration.
• There is a critical need to accelerate the discovery of targeted ADPKD therapies to match progress in other renal diseases.