PROJECT SUMMARY – RESEARCH PROJECT Nephrolithiasis is a chronic disease characterized by recurrent symptomatic events that are both painful and expensive. Despite concerning epidemiological trends showing a higher incidence of disease and more frequent recurrence rates in youth aged 21 years and younger as compared to adults, a strong evidence base upon which to develop individualized management strategies for youth with nephrolithiasis is lacking. The overarching objective of the Personalizing Outcomes of Nephrolithiasis in Youth (PONY) P20 Center is to strengthen patient- centered knowledge and improve personalized management of youth with nephrolithiasis. We will generate new knowledge about two distinct but related common clinical scenarios: 1) the natural history of non-obstructive kidney stones, and 2) the post-operative patient-reported experience following ureteroscopy surgery for stones. To achieve this mission, we will leverage ongoing partnerships among Dr. Gregory Tasian (PI at Children’s Hospital of Philadelphia, Dr Jonathan Ellison (early-stage investigator at Children’s Wisconsin), Dr. David Chu (early-stage investigator at Lurie Children’s Hospital of Chicago), and Dr. Jing Huang (biostatistician at Children’s Hospital of Philadelphia). Specifically, this project will be supported by the resources generated by Dr. Tasian’s research program, in particular the robust infrastructure of the Pediatric KIDney Stone (PKIDS) Care Improvement Network and data generated two NIDDK-supported Urinary Stone Disease Research Network studies: the Prevention of Urinary Stones with Hydration (PUSH) trial and the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS). In Aim 1, we will develop and validate a risk prediction model for symptomatic stone events for youth with non-obstructive stones. Model development will leverage PKIDS trial data, which will be further augmented by linkage with the PCORnet common data model, providing an additional 18 months of follow-up beyond the PKIDS trial. The prediction model will be externally validated among youth in the PUSH trial. We expect to evaluate this prediction tool in a future R01-supported hybrid implementation- effectiveness trial within the PKIDS Care Improvement Network comparing the prediction tool against usual care for non-obstructing nephrolithiasis. In Aim 2, we will apply group-based trajectory modeling to differentiate distinct longitudinal trajectory groups of post-operative pain intensity, pain interference, and urinary symptoms following ureteroscopic surgery for stones. These unique trajectory groups will identify subgroups of youth at high risk for severe pain and urinary symptoms after surgery. We will determine the predictors and consequences of group membership to help with risk stratification. This modeling approach will be applied first to youth in the PKIDS trial, then repeated among youth in STENTS. We expect to leverage our findings in a future R01-supported prag...