Stepping stones to targeted treatment of primary hyperoxaluria

The primary hyperoxalurias (PHs) are a group of rare genetic disorders affecting glyoxylate metabolism, leading to excessive oxalate production, a metabolic end-product. This overproduction can result in nephrocalcinosis, recurrent kidney stone formation and kidney failure. The clinical course of PH is highly variable, ranging from patients developing kidney failure in infancy to occasional kidney stone episodes in adulthood. Until recently, treatment options were limited, with liver transplantation being the only curative approach available for affected individuals. However, novel therapeutic modalities based on RNA interference (RNAi) have emerged, transforming the therapeutic landscape for PH1. The various chapters of this thesis examine the clinical characteristics, disease course and optimal treatment strategies for patients with PH. Furthermore, they explore global access to PH management, including a controlled access strategy for expensive RNAi therapy.