Implementing Precision Medicine for Glomerular Diseases in the Nephrotic Syndrome Study Network

About This Grant

ABSTRACT Over the past 14 years, the Nephrotic Syndrome Study Network (NEPTUNE) has established a cohort of more than 850 pediatric and adult patients with proteinuric glomerular diseases characterized with deep clinical, histological, genetic, and molecular profiles, and with long term outcomes under standard of care. The multi- scalar datasets from these patients have been combined into the NEPTUNE Knowledge Network (NKN) and have been enriched by more than 220 ancillary studies that have investigated disease mechanisms in discrete patient subgroups as starting points to stratify patients for targeted therapies. The NEPTUNE infrastructure has matured sufficiently so that multi-scalar information can be rapidly generated by the NEPTUNE analytical units along the genotype-phenotype continuum. These data allow for the rapid definition of an individual participant’s molecular disease processes at the time of presentation exposing the mechanistic heterogeneity of glomerular disease for targeted treatment intervention. With these key pre-requisites in place, NEPTUNE is now able to test the precision medicine concept in glomerular disease with the goal of identifying the right treatment for the right patient at the right time. This precision medicine study will utilize the NKN to develop and deploy two treatment response prediction models: (1) Predicting response to current Kidney Disease Improving Global Outcomes (KDIGO) recommended standard of care treatments of glomerular diseases with the aim of answering patients’ questions about which currently available treatment is optimal for them; (2) Predicting in the NEPTUNE Match study framework whether molecular pathways underlying an individual patient's glomerular disease are likely to be targeted by a specific clinical trial intervention The trial recommendations are provided to study participants and site investigators to facilitate selection of a molecular matched trial. Impact of NEPTUNE Match on patients and trial outcomes is prospectively ascertained. NEPTUNE Match has established partnerships with academic and industry lead clinical trials supporting the patient stratification for targeted NS trials in a precompetitive manner across diverse trials in glomerular disease and will continue to expand capacity and breath in response to the rapidly evolving trial space in glomerular diseases.