The most common genetic cause of chronic kidney disease is autosomal dominant polycystic kidney disease (ADPKD). Up to 70% of patients with ADPKD progress to end-stage kidney disease (ESKD) by age 65 years. Kidney function may remain stable for years following diagnosis, however, patients with ADPKD may experience debilitating symptoms such as pain related to growth and enlargement of kidney cysts. Patients in this population are also at risk for extrarenal complications, including stroke associated with ruptured intracranial aneurysm and severe polycystic liver disease.
Lifestyle interventions such as restriction of salt intake as well as therapeutic agents such as tolvaptan have been shown to improve kidney function and total kidney volume. Other outcomes of importance to patients with ADPKD and their caregivers that include kidney pain, fatigue, and anxiety/psychosocial distress are rarely reported in trials among ADPKD patients.
The SONG-PKD (Standardized Outcomes in Nephrology—Polycystic Kidney Disease) initiative was designed to generate consensus among patients, caregivers, and health professionals on important outcomes to be reported in trials in ADPKD. The initiative aimed to inform the development of a core outcome set, defined as an “agreed minimum set of outcomes to be reported in all trials,” resulting in improved consistency in outcome reporting across trials to improve shared decision making.
Yeoungipee Cho, PhD, and colleagues conducted an international two-round online Delphi survey, an internationally accepted approach to establish consensus on core outcome sets for trials in nephrology and other disciplines. The survey was conducted in English, French, and Korean languages. Results were reported in the American Journal of Kidney Diseases [2020;76(3):361-373].
Patients, caregivers, and health professionals with experience in ADPKD were eligible to participate in the survey. Patients and caregivers aged ≥18 years of age included patients with ADPKD across all stages of CKD (stages 1-5; hemodialysis or peritoneal dialysis; and transplantation) and family members and friends. Health professionals included physicians (nephrologists, hepatologists, surgeons, and geneticists), nurses, allied health professionals, researchers, policy makers, industry, and regulators.
The survey participants completed a 9-point Likert scale (7-9 indicating critical importance) and a Best-Worst scale (BWS). The absolute and relative importance of outcomes were assessed, and comments were analyzed thematically. The survey was administered in two rounds.
In round 1, participants scored the importance of each of 41 outcome domains. A total of 1014 participants from 56 countries completed the survey in round 1: 603 (60%) patients/caregivers and 411 (40%) health professionals. Seventeen outcomes were included in round 2; participants could review their own scores from round 1. In round 2, 713 participants (70% overall retention rate) from 47 countries completed the survey: 406 (57%) patients/caregivers and 307 (63%) health professionals.
Of the 406 patients/caregivers who completed both rounds of the survey, 74% (n=275) were not receiving kidney replacement therapy, 2% (n=7) were receiving peritoneal dialysis, 6% (n=22) were receiving hemodialysis, and 18% (n=68) were kidney transplant recipients. The patients were from 23 countries, including the Republic of Korea, United Kingdom, United States, Australia, and Canada. Of the 307 health professionals who completed both rounds, 70% (n=214) were nephrologists, 12% (n=36) were researchers, and 10% (n=32) were nurses. The health professionals were from 41 countries, including Australia, France, United States, United Kingdom, Republic of Korea, and Canada.
In round 1, the top five outcomes with the highest mean scores for patients/caregivers were kidney function, defined for participants as the ability of the kidney to remove waste from the body and balance fluids, (8.5), ESKD (8.4), cerebral aneurysm (8.0), kidney cyst size/growth (8.0), and blood pressure (7.9). For health professionals, the top 5 outcomes were kidney function (8.4), ESKD (8.4), death (7.8), cerebral aneurysm (7.5), and blood pressure (7.5). In round 2, the top five prioritized outcomes from all participants were kidney function (8.6), ESKD (8.6), death (7.9), blood pressure (7.9), and kidney cyst size/growth (7.8).
In the BWS survey, ESKD was identified by both stakeholder groups as the most important outcome; however, there were differences in the subsequent order of outcomes. The patient/caregiver groups prioritized (in descending order) ESKD, kidney function, cerebral aneurysm, cardiovascular disease, and blood pressure. Among health professionals, death was considered the second most important outcome, followed by kidney function and cardiovascular disease. Patients and caregivers identified chronic pain, kidney cyst size/growth, and kidney cyst pain/bleeding/infection as being as important as death.
The survey results identified seven themes that reflected the reasons for and changes and differences in the rating of outcomes: (1) protecting life and health; (2) directly encountering life-threatening and debilitating consequences; (3) specificity to ADPKD; (4) optimizing and extending quality of life; (5) hidden suffering; (6) destroying self-confidence; and (7) lost opportunities.
The researchers cited potential limitations to the findings, including the survey not measuring details such as ethnicity or stage of CKD to allow subgroup analysis of outcomes, and the online mode of administration of the survey not allowing for involvement from those without access to the internet or with limited computer literacy.
In conclusion, the authors said, “The most important outcomes to patients/caregivers and health professionals were ESKD, kidney function, cerebral aneurysm, and blood pressure. Kidney cyst pain and life participation were the most highly prioritized patient-reported outcomes by patients/caregivers. Before finalizing the core set of outcome domains, public consultation will be sought through a consensus workshop involving patients, caregivers, and health professionals, and any members of the public will be able to access the proposed core outcomes over a 2-week time frame and provide feedback through the SONG website. All input will be reviewed and considered by the SONG-PKD Steering Group to establish a core outcome set. Although the elements discussed as end points in this survey have been studied previously, they have generally been inconsistently reported. Therefore, when a core outcome set has been identified, outcomes measures will be developed through a systematic process (systematic review and workshop) before its implementation in trials. Establishing and implementing a core outcome set will help improve the relevance and consistency of evidence to better inform shared decision making for patients with ADPKD.”
- Results of an international two-round online DELPHI survey designed to identify important consensus-based core outcome domains in trials involving patients with autosomal dominant polycystic kidney disease (ADPKD) were reported.
- Survey respondents included patients and caregivers as well as health professionals; both groups identified kidney function, end-stage kidney disease, death, blood pressure, kidney cyst size/growth, and cerebral aneurysm as the top six outcomes.
- The highest rated patient-reported outcome was kidney cyst-related pain.