Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease, affecting approximately 1 in 400 to 1 in 1,000 individuals. Mutations in PKD1 and PKD2, encoding polycystin-1 and polycystin-2, were identified in landmark positional cloning studies published in Cell and Nature Genetics in 1994 and 1996, respectively, establishing the molecular basis of this condition. The ISN has engaged with ADPKD research through its KDIGO work groups and through Kidney International, which has published extensively on ADPKD pathophysiology and treatment.
ISN (International Society of Nephrology) has facilitated international collaboration on ADPKD disease monitoring through endorsement of total kidney volume (TKV) measurement as the principal imaging biomarker, as described in the Mayo Clinic imaging classification (Irazabal et al., Journal of the American Society of Nephrology, 2015). Height-adjusted TKV and MRI-based growth rate calculations stratify patients into rapidly progressive phenotypes eligible for disease-modifying therapy.
The TEMPO 3:4 trial (Torres et al., New England Journal of Medicine, 2012) enrolled 1,445 patients with ADPKD and demonstrated that tolvaptan, a vasopressin V2 receptor antagonist, significantly slowed TKV growth rate and attenuated the annual rate of eGFR decline compared to placebo over three years. The REPRISE trial (Torres et al., New England Journal of Medicine, 2017) subsequently confirmed these benefits in patients with more advanced CKD (eGFR 25 to 65 mL/min/1.73 m²), supporting regulatory approval in multiple jurisdictions.
Hepatotoxicity associated with tolvaptan, identified in the TEMPO 3:4 trial and further characterized in post-marketing surveillance, led to FDA and EMA risk communication measures requiring monthly liver function monitoring. The risk-benefit assessment supporting tolvaptan use in rapidly progressive ADPKD patients is detailed in ISN-aligned practice statements and the 2023 KDIGO ADPKD Practice Points document.
The International Society of Nephrology has followed developments in additional ADPKD therapeutic targets. mTOR inhibitors including everolimus and sirolimus did not demonstrate clinically meaningful slowing of TKV growth in phase 3 trials (Serra et al., New England Journal of Medicine, 2010; Walz et al., New England Journal of Medicine, 2010). Somatostatin analogues, including octreotide and lanreotide, have shown TKV-slowing effects in the DIPAK-1 trial (Meijer et al., Journal of the American Medical Association Internal Medicine, 2016), representing an alternative approach currently under further investigation.