Navigating Gaps in ADPKD Research: Early Risk Modeling, Real-World Treatment, and Patient Partnerships

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disorder and a leading cause of renal failure. While significant progress has been made in understanding ADPKD progression and treatment, gaps remain in early prognostic modeling, treatment implementation, and patient engagement. This dissertation addresses these challenges in three different studies. First, a longitudinal analysis of the Early PKD Observational Cohort (EPOC) demonstrates that kidney growth in pediatric and young adult ADPKD follows heterogenous nonlinear trajectories, with key risk factors in progression. This work highlights the need for age-specific risk stratification to predict long-term outcomes. Second, a real-world study of tolvaptan use in ADPKD patients across two U.S. medical centers provides insights into tolerability and adherence. Findings reveal a strong preference for lower-than-trial tolvaptan dosages in practice, underscoring the need for side-effect management and individualized dosing to optimize long-term use. Third, an evaluation of patient engagement in the PKD Research Resource Consortium (PKD RRC) explores how structured patient involvement can improve the development and accessibility of research resources. This study presents a novel conceptual framework for integrating patient perspectives into research design and infrastructure, positioning patient engagement as a critical research resource. Together, these studies aim to advance early ADPKD risk stratification, optimize treatment implementation, and integrate patient voices into research infrastructure. By bridging research and clinical care, this work aims to improve both scientific rigor and patient-centered outcomes in ADPKD management.