Patient and Caregiver Perspective on PRO-Kid Quality of Life Tool

As patients who grew up with CKD, mothers to sons with X-linked Alport syndrome, and staff members of the Alport Syndrome Foundation who frequently speak with other patients and caregivers, we understand that many important aspects of childhood can be negatively affected by living with CKD. With the article, Validation of Patient-Reported Outcome Measure in Pediatric CKD (PRO-Kid), published in this issue of CJASN, we commend Matsuda-Abedini et al.1 for addressing the need for improved quality-of-life (QOL) tools in CKD treatment and for clinical trials. We find the strengths of the study approach to be the sample size, inclusion of input from patients and caregivers, and the willingness to design and vet a much-needed tool. We also find benefit in the nonburdensome number of questions and the attention to age-appropriate phrasing. While a valuable baseline assessment for CKD, the PRO-Kid tool has limitations we believe should be considered. Focusing on the authors' statement, "Outcomes that are most relevant to young CKD patients are often omitted from clinical trials that evaluate interventions to improve care in this population, at least partly due to the absence of validated tools that quantify these patient-reported outcomes," we hope to share insights regarding which context(s) the PRO-Kid tool has the most value and how the tool may be enhanced. From our perspective, a "one size does not fit all" approach should be applied to clinical study design and QOL tools. Children with kidney diseases that progress over time then suddenly become an unstoppable train have different experiences from those who live with congenital abnormalities causing CKD. Thankfully, there are clinical studies exploring medications for each of these groups separately. It is worth noting that the median eGFR of participants in the related article was 27.4 ml/min per 1.73 m2, reflecting severe stage 4 CKD. In addition, 26% of participants were already on dialysis, reflecting ESKD or stage 5 CKD. Thus, questions related to symptoms of nausea, itching, lack of appetite, constipation, problems thinking, changes in food taste, and trouble breathing, all associated with these later CKD stages, are important to capture. However, they represent 50% of the tool's questions and typically would not be relevant to the experience of patients in CKD stages 1–3, with some exceptions that can be addressed on the basis of the study patient population target. Our shared goal is to advance clinical trials with therapies developed to help patients avoid ESKD altogether or delay onset. Fortunately, the pipeline of CKD clinical studies increasingly includes pediatric patients who are early in their disease state yet at high risk of progression. It is important to support these critical studies with meaningful QOL tools. For these reasons, we believe the PRO-Kid tool would be enhanced by more specificity in several of the questions and the addition of questions that reflect all CKD stages. For example, with patients with CKD widely prescribed renin-angiotensin-aldosterone-system blockers, questions related to dizziness/light-headedness should be considered. Our experience indicates this is a common problem at all ages and stages of disease and affects QOL in pediatric patients. More specificity could also lead to better understanding of fatigue symptoms. The PRO-Kid tool inquires about "feeling tired," which has the connotation of desire to sleep. Feeling as though "I do not want to do anything or participate in activities" is different and can be associated with physical and/or psychosocial effects of medications—distinctions we see as critical to effective care. In addition, in Alport syndrome and other rare CKDs, such as Fabry disease, listening fatigue from associated hearing loss is another common form of feeling "tired," but would not be distinguished with the PRO-Kid tool. We believe further refinement would encourage better follow-up questions from treating physicians, resulting in improved care. With a variety of medications prescribed across the CKD spectrum, perhaps a simple question allowing a thumbs-up or thumbs-down response related to how a medication makes the patient feel would lead to more in-depth questioning and helpful insights for the clinician. For example, a patient with late-stage CKD taking medication to treat constipation due to phosphate binders may find the medication helps them feel better. Conversely, an early-stage patient taking a renin-angiotensin-aldosterone-system inhibitor may indicate a thumbs-down, with the opportunity for the physician to inquire specifically how the medication makes them feel. This could be valuable in ascertaining effects of a clinical trial drug as well. New studies are layering novel treatments on top of the standard of care, so capturing the new onset of or change in symptoms can be critical. PRO-Kid is valuable as a novel tool for clinicians treating pediatric patients with CKD. We believe it can be enhanced for both the clinical trial and routine care settings by increased specificity and questions that include the common issues inherent across all CKD stages.