On August 29, 2023, an externally led PFDD (EL-PFDD) virtual meeting for ARPKD hosted individuals with ARPKD community members (ie, caregivers, family members, researchers, clinicians, drug developers, and government officials from FDA). The virtual meeting allowed ARPKD to submit responses through live online polls, telephone call-ins, comments through an online portal, and live moderated discussion. Subsequently, the video and audio recordings were transcribed⁸ (see Item S1).

Qualitative insights and other perspectives were collected and included in a voice of the patient⁸ report and an ancillary Scientific Report. Given that this was the first ARPKD-focused PFDD initiative, we set forth to compare the themes/outcomes between the ARPKD EL-PFDD effort and previous Standard Outcome in Nephrology Group (SONG) outputs, including SONG-Transplant, SONG-Kids, and SONG-PKD.9, 10, 11, 12, 13, 14

SONG initiatives relevant to the ARPKD patient and caregiver community were collected and analyzed, including SONG-Transplant, SONG-Kids, and SONG-PKD. Core outcomes and others of significance noted by the authors were collated and separated into physical and emotional outcomes, and variables with similarities were grouped by organ system. A thematic synthesis was conducted (BS and DO) between each SONG initiative and the themes identified in the EL-PFDD meeting voice of the patient report and accompanying planning survey. A constant comparative analysis was used to highlight main themes and note similar concept links and items unique to each group. Subsequently, participant-identified priority outcomes were combined to better understand discrepancies and compare participant characteristics. To better align categories across various participant description tables, we combined categories of age range, disease stage, and level of education. For the participant demographics from the EL-PFDD meeting, we used the self-reported information provided by patient and caregiver participants in the meeting surveys. The patient and participant demographics for SONG-Transplant, SONG-Kids, and SONG-PKD were obtained from each respective study.

SONG-Kids discussed themes such as conflict of decision-making between parents/caregivers and clinicians and including the child’s voice in the decision-making process. In addition, the SONG-Kids identified core outcomes such as life participation, survival, kidney function, and infection.^15,16 The middle and outer tiers brought to attention outcomes such as participation in daily activities (ie, travel, work, and school), multiorgan involvement, mental health, cognition, self-esteem, pain, sleep, and financial impact.^15,16 The SONG-Kids initiative did not differentiate outcomes between different pediatric kidney diseases.

The EL-PFDD included participants in the 0-5 years age group. Earlier diagnosis of ARPKD often is indicative of more severe disease progression.³ This is in contrast to SONG-Kids, in which the youngest reported participants were in the 6-18 years age group. The EL-PFDD’s discussion focused on the heterogeneous presentation of ARPKD, which impacts children differently. Furthermore, discussions revolved around disease-related health concerns, progression to liver and spleen involvement, disease burden, barriers to available treatments, and adjunctive/supportive therapies. Participants discussed the emotional toll of limiting childhood activities and the unmet needs of clinical trials and treatment options. Families and patients were concerned about the lack of available treatment options to halt the progressive nature of ARPKD. Parents shared challenges with administering medications in large volumes to their children. Another theme covered in the EL-PFDD from the adolescent patient perspective was growing up with ARPKD and the transition from childhood into adulthood.

Both EL-PFDD and SONG-Kids (Fig 1) discussed the importance of graft function, kidney health, pain, self-esteem, life participation, infection, and blood pressure control. In addition, both initiatives addressed how each disease and subsequent complications limited participation in school and childhood activities, such as playing sports and interaction with peers. The EL-PFDD emphasized that an enlarged abdomen and short stature affected self-esteem. The concern of spleen ruptures limited childhood activities such as riding a bicycle or playing sports. Both groups discussed preparing children to care for themselves and complying with their complex treatment regimens. There was an emphasis on the difficulty of long-term decisions and family planning for both patients and their parents.

The SONG-Tx identified core outcomes such as graft function, increased risk of cardiovascular disease and cancer, infection, life participation, and mortality.¹⁹ The middle and outer tiers focused on physical and disease states related to transplants and psychosocial impacts, such as the ability to work, blood pressure, hospitalization, mood disorders, weight gain, and impact on the family.¹⁹ SONG-Tx’s participants were 18 years and older.

A central theme of the EL-PFDD was that transplant was not a cure but rather another disease state with its own set of complications, as a transplant could place patients at risk for medication side effects, cancer, and infections. Anti-rejection medications affect numerous organ systems, and patients with ARPKD might require multiple transplants, including kidney and liver. One patient participant discussed how a transplant would limit her dream of becoming a veterinarian due to the high infection risks associated with post-transplant immunosuppressive medications. Parents raised concerns that their child most likely would need another kidney transplant later in life because the first one was completed in early childhood. Participants advocated for therapies to delay the need for transplants and preserve current kidney and liver function.

Nevertheless, the EL-PFDD and SONG-Tx discussed (Fig 2) disease inevitability, multiorgan involvement, treatment complications and risks, and blood pressure. Both initiatives highlighted the importance of adequate kidney function, concerns with dialysis modality and burden, graft function and loss, immunosuppression, and cancer risks. There was mention of appearance, weight gain, life participation, mortality, mental health, family planning, sleep, pain, and impact on family and friends.

The SONG-PKD initiative included adult (18 years and older) participants with ARPKD, caregivers, and clinicians. SONG-PKD identified core outcomes such as kidney function, mortality, cyst pain, and cardiovascular disease.^17,18 Middle and outcomes included blood pressure, cyst bleeding/infection/growth, mental health, hospitalizations, sexual function, and liver involvement.^17,18 There was also a discussion of the various disease complications, such as post-transplant diabetes, weight changes, lipids, mood, headaches, and diverticulitis. The SONG-PKD discussed themes such as fertility, problems with employment, hidden suffering, being overwhelmed by decision-making, and financial impact.

EL-PFDD discussed ARPKD issues encountered in early childhood and the transition into adulthood. Furthermore, there was mention of failure to thrive, developmental delays, cognitive and behavioral issues, and the impact on childhood activities. Patients and caregivers were queried about alternative, supportive therapies and programs such as psychotherapy, diet, and acupuncture. Parents raised concerns about helping their children take care of themselves.

The EL-PFDD and SONG-PKD (Fig 3) covered disease burden and inevitability, heterogeneous disease presentation, multiple organ system involvement, and treatment complications and risks. Both groups discussed blood pressure, kidney function, cysts, life participation, body image, mortality, and infections. There was mention of how the disease impacted self-esteem, mental health, and relationships with family and friends. Both initiatives brought up symptoms and complications of the disease, such as itchy skin, breathing problems, and an enlarged abdomen.

Belle Soyfer, PharmD, MLS, Sorin Fedeles, MBA, PhD, Wendy Ruyle, MLS, Elise Hoover, MPH, Max C. Liebau, MD, Erum A. Hartung, MD, MTR, Katherine M. Dell, MD, Lisa M. Guay-Woodford, MD, Ronald D. Perrone, MD, and Dorothee Oberdhan, PhD

Dr Liebau was supported by the German Federal Ministry of Research and Education (NEOCYST consortium, BMBF grant 01GM2203D) and by the EU Horizon program (TheRaCil consortium, EU grant agreement 101080717). Dr Guay-Woodford is supported by NIH U54 DK 126087. Dr Hartung is supported by the National Institutes of Health (2R01 DK114425-04A1, 5 R03 DK127132-02), U.S. Food and Drug Administration (1R01FD008225-01), PKD Foundation, and Benjamin Banks, Jr memorial foundation. Critical Path Institute is supported by the Food and Drug Administration (FDA) of the Department of Health and Human Services (HHS) and is 56% funded by the FDA/HHS, totaling $23,740,424, and 44% funded by non-government source(s), totaling $18,881,611. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, FDA/HHS or the U.S. Government. Additional support for the Polycystic Kidney Disease Outcomes Consortium (PKDOC) comes from membership fees paid by members of PKDOC.

Sorin Fedeles reports patents and royalties from Yale University; has ownership interest and serves on the SAB of Renasant Bio.; consulting agreements with Retex Pharma, Ren Bio, and Prolix Biotherapeutics; and is an employee of the Critical Path Institute. Wendy Ruyle is an employee of the Critical Path Institute. Max Liebau has received grants from the German Federal Ministry for Education and Research, EU Horizon and the German Research Council, and the PKD Foundation; speaker fees from Rhythm (paid to University Hospital Cologne); and a consulting fee from Otsuka (paid to University Hospital Cologne). Katherine Dell is supported by NIH R01 -DK114425 and the PKD Foundation. Lisa Guay Woodford is a compensated consultant for Otsuka Pharmaceuticals and Estuary Biotherapeutics. Ronald D. Perrone has been on the Steering Committees for AbbVie∗ and Vertex∗; a consultant for Otsuka∗, Retex∗, Estuary, SouffleTx, Sanofi-Genzyme, Regenephro, and Regulus∗; and a section editor for Cystic Kidney Disease: UpToDate. ∗Paid to Tufts Medical Center. The remaining authors have no financial interests to disclose.

Received February 5, 2025. Evaluated by 1 external peer reviewers, with direct editorial input from the Associate Editor and the Editor-in-Chief. Accepted in revised form June 17, 2025.