#3124 How well do risk assessment guidelines perform for ADPKD?

Abstract Background and Aims The approval of Tolvaptan for treatment of ADPKD heralds a new era when mechanism-based therapy is now possible. However, Tolvaptan is an expensive drug associated with potentially serious side effects and is currently reserved for patients at high-risk for progression to ESKD. Two sets of risk assessment guidelines for ADPKD are now available based on the consensus of two panels of nephrologists from Canada and Europe. However, how well do these guidelines perform in risk assessment has not been formally assessed. Method We conducted a prospective study in 474 patients with typical imaging pattern of ADPKD by MRI who also had detailed clinical and laboratory data. We used age- and height-adjusted total kidney volume to derive the Mayo Clinic Imaging Class as a “gold-standard” for risk assessment (i.e. low-risk: 1A-1B; high-risk: 1C-1E). We then applied the revised Canadian guidelines (Can J Kidney Health Dis. 2018) and the updated European guidelines (NDT 2022) to our patient cohort to assess their performance. Results The study cohort consisted of 286/474 (60%) high-risk patients with MCIC 1C-1E. Applying the updated Canadian risk assessment algorithm resulted in exclusion of 245/474 (52%) patients including 86/286 (30%) of the high-risk patients. The resultant cohort (229/474) was enriched with 88% high-risk patients but also included 12% of low-risk patients. The updated European guidelines provide a 3-step hierarchal algorithm, when applied resulted in exclusion of 55% (157/286) of high-risk patients. During the last step, 122 patients could not be classified due to a lack of eGFR slope information. The resultant cohort (180/474) was enriched with 72% high-risk patients but also included 28%(51/180) of low-risk patients. Conclusion Risk assessment in ADPKD is an evolving process that needs to be redefined by new clinical data and test technologies. Clinical guidelines should be evaluated using real-life data and those that enrich high-risk patients while minimizing low-risk patients have the most clinical utility