Systematic review of outcomes reported in clinical research on nephronophthisis: how do they align with SONG Kids priorities?

Abstract Background Nephronophthisis (NPH) is a rare hereditary cystic kidney disease, characterized by a highly variable clinical and genetic presentation, accounting for up to 10% of kidney failure in children. Despite advances in understanding its molecular basis and phenotypic spectrum, no causative therapies exist, and clinical trials remain absent. To support future treatment development, patient-reported outcome measures (PROMs) tailored to NPH should be defined to prioritize outcomes meaningful to patients and families. Objectives This study aimed to analyze the use of clinical data, surrogate parameters, and patient-reported outcomes in NPH research to date, with a focus on the Standardized Outcomes in Nephrology (SONG) project outcomes validated for children with chronic kidney disease (SONG Kids). Data sources A systematic search of the MEDLINE database was conducted for NPH studies. Study eligibility criteria Studies published after 1988, written in English, reporting at least one human clinical outcome, with a sample size of n ≥ 4, and using original data were considered eligible. Results A total of 1066 records were retrieved through the search, of which 821 full-text reports were assessed for eligibility. Of these, 90 studies met eligibility criteria and were included in the review. While 100% of the studies reported clinical outcomes and 85% included surrogate parameter, only 41% examined patient-reported outcomes. Overlap between the SONG Kids outcome set and the outcomes identified in this study was moderate. Only 20 studies reported more than one SONG core outcome, while 24% and 66% of studies reported at least one middle tier or outer tier outcome, respectively. None of these studies used instruments validated for NPH. Limitations The majority of studies focused primarily on molecular and genetic aspects, with clinical outcomes addressed only as a secondary consideration. The review incorporated only one prospective study, while the remaining studies were retrospective in nature. Differentiation between outcomes reported by children and those reported by parents was not possible in the included studies; this important distinction must be taken into account in the development of future PROMs for NPH. Conclusions and implications of key findings Studies in NPH addressed both clinical outcomes and surrogate parameters, but there is a notable absence of measures related to life participation and patient-reported outcomes. Disease group-specific instruments fall short in adequately reflecting the symptoms of individual diseases, emphasizing the necessity for the development of disease-specific PROMs for NPH. Open Science Framework (OSF) registration: https://doi.org/10.17605/OSF.IO/658BR Graphical abstract