Autosomal Dominant Polycystic Kidney Disease: From Pathophysiology of Cystogenesis to Advances in the Treatment.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing molecular mechanisms and therapeutic targets with no new primary human data.
PubMed 35328738 · doi:10.3390/ijms23063317
What was done
The authors reviewed the molecular and cellular mechanisms underlying cystogenesis in autosomal dominant polycystic kidney disease (ADPKD), along with emerging pharmacological therapies from cellular, animal, and ongoing clinical trial investigations.
What was found
The abstract reports no quantitative trial data. It describes key pathophysiological drivers of cyst expansion, including mutations in PKD1 and PKD2, intracellular calcium depletion, cyclic adenosine monophosphate (cAMP) accumulation, aberrant signaling (MAPK/ERK, mTOR, PI3K, AMPK, JAK/STAT, NF-kB), inflammatory recruitment, and metabolic reprogramming (defective glucose metabolism, impaired beta-oxidation, and mitochondrial dysfunction). It notes that while tolvaptan slows disease progression, tolerability is limited by aquaretic side effects, motivating ongoing randomized controlled trials targeting these alternative pathways.
Why it matters
This review provides an overview of the broad molecular network driving ADPKD cyst growth and outlines therapeutic targets beyond vasopressin V2 receptor antagonism.
Limits
The abstract describes a broad narrative synthesis rather than a systematic review or meta-analysis. No quantitative efficacy, safety metrics, or trial sample sizes are reported in the abstract.
Cited by
- contradicts Cysts are a mechanism by which the body encapsulates toxic substances.