[Review] Autosomal Dominant Polycystic Kidney Disease

Why It Matters

Early, precise diagnosis and disease‑modifying therapy can delay end‑stage kidney failure, reducing individual suffering and the economic burden on health systems. The evolving therapeutic landscape underscores the need for multidisciplinary, patient‑centered management.

Key Takeaways

• ADPKD is leading genetic cause of chronic kidney disease
• Tolvaptan slows progression in high‑risk patients
• Genetic testing refines prognosis and guides therapy
• Multidisciplinary care essential for extra‑renal complications
• Imaging advances improve early diagnosis and monitoring

Pulse Analysis

ADPKD accounts for roughly 5‑10% of end‑stage renal disease cases, translating into billions of dollars in annual healthcare expenditures across Europe and the United States. Population‑based sequencing studies have revealed a prevalence of 1 in 400 to 1,000, with considerable variability driven by PKD1, PKD2, and emerging atypical genes such as GANAB and DNAJB11. The disease’s systemic nature—encompassing hypertension, hepatic cysts, and vascular anomalies—creates a complex clinical picture that challenges traditional nephrology workflows, prompting a shift toward integrated care models that address both renal and extra‑renal manifestations.

Advances in imaging, particularly magnetic resonance volumetry, now allow clinicians to quantify total kidney volume (TKV) with high precision, a surrogate marker strongly linked to disease trajectory. Coupled with genotype‑phenotype correlations, these tools enable risk stratification at an earlier stage than serum creatinine alone. The 2025 KDIGO guideline recommends incorporating TKV and pathogenic variant data into treatment algorithms, emphasizing shared decision‑making. Genetic panels that include rare alleles (e.g., ALG8, ALG9, IFT140) further refine prognostic estimates, helping identify patients who may benefit most from early intervention.

Therapeutically, tolvaptan remains the only approved disease‑modifying agent, demonstrating a 30‑35% reduction in the rate of eGFR decline in high‑risk cohorts. Ongoing trials explore novel pathways—cAMP signaling, metabolic reprogramming, and ciliary function—offering hope for additional oral agents with fewer side effects. Concurrently, lifestyle interventions such as weight management and protein moderation have shown modest benefits in slowing cyst growth. The future of ADPKD care lies in a holistic, multidisciplinary framework that blends precision genetics, advanced imaging, pharmacologic innovation, and patient‑focused education to curb progression and improve quality of life.