**Background:** Autosomal dominant polycystic kidney disease (ADPKD) is a progressive systemic disease in which approximately 60% of individuals experience acute and/or chronic abdominal, back, or flank pain regardless of age. Pain is the most frequent symptom leading to diagnosis and has been identified by both patients and clinicians as the most important patient-centric outcome. However, unclear conceptualization of pain has led to inconsistent measurement across studies. The objective was to develop a PRO instrument to assess ADPKD-associated pain and discomfort through establishment of a meaningful conceptual framework and robust content and construct validation.
**Methods:** Development followed standard PRO instrument methods. Qualitative work included a literature review (117 articles identified), advisory meetings with 26 clinical experts from North America and Europe, and 46 focus groups conducted across 18 countries from June 2012 through October 2013 involving 293 patients (137 male, 156 female). Initial focus groups (n=125) revealed three distinct pain types: dull kidney pain, fullness/discomfort, and sharp kidney pain. Three rounds of cognitive debriefing interviews were conducted (round 1: n=10; round 2: n=5; round 3: n=5) from December 2013 through March 2015. The quantitative evaluation used an online survey of 298 participants (mean age 48 years, SD 13; 80% female; 87% White) recruited via the PKD Foundation. CKD stage distribution was: stage 1 (27%), stage 2 (20%), stage 3 (30%), stage 4 (11%), stage 5 (9%). Participants completed the ADPKD-PDS, ADPKD-IS, BPI-SF, and SF-12v2 at baseline. A follow-up survey was completed by 108 participants approximately 25 days later. Analyses included confirmatory factor analysis, item response theory, differential item function analysis, convergent validity, test-retest reliability, and anchor-based responsiveness analysis.
**Key Results:** The final measurement model demonstrated excellent fit: for pain severity, CFI=0.99, NNFI=0.99, RMSEA=0.041 (90% CI 0.000 to 0.069), SRMR=0.024; for pain interference, CFI=0.99, NNFI=0.99, RMSEA=0.032 (90% CI 0.000 to 0.057), SRMR=0.015. The final ADPKD-PDS contains 20 items across seven domains: four Pain Severity domains (Dull Pain Severity, Sharp Pain Severity, Discomfort Severity, Overall Pain and Discomfort Severity) and three Pain Interference domains (Dull Pain Interference, Sharp Pain Interference, Discomfort Interference). Floor effects ranged from 22% to 70% across items; ceiling effects exceeded 10% for only one item (Sharp Pain Severity at its worst). Clinically meaningful change thresholds were established: Overall Pain Severity=0.2, Dull Pain Severity=0.5, Sharp Pain Severity=0.5, Discomfort Severity=0.5, Dull Pain Interference=0.2, Sharp Pain Interference=1.0, Discomfort Interference=0.2. The ADPKD-PDS showed greater pain severity and interference at more advanced CKD stages, following clinically expected patterns. Only 13% (n=38) of participants had useable total kidney volume information.
**Clinical Implications:** The ADPKD-PDS is the first dedicated PRO tool for systematically assessing pain and discomfort across CKD stages in ADPKD. It addresses the tendency of patients to normalize and under-report chronic pain by prompting reflection on ADPKD-specific pain types and their interference with daily life. The instrument captures not only the core ADPKD outcome of pain but also impacts on physical activities, social interactions, rest, and enjoyment of life. The involvement of focus groups across diverse geographical and cultural regions suggests generalizability to the global ADPKD population. Limitations include a predominantly female sample (80%), a short 7-day recall period that may under-capture episodic sharp pain, recruitment from a single country for the quantitative survey (United States), and lack of detailed pain medication data. A pediatric version is still needed. The instrument is available via Mapi Research Trust.