Primary hyperoxaluria type 1: time for prime time?

Oxalate crystals in the kidney were first described in 1925. Since then, many major milestones have been reached in the understanding of genetic primary hyperoxaluria(s). Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease due to a mutation in the AGXT gene, which encodes the hepatic peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT), inducing excess oxalate production and further kidney stones, nephrocalcinosis and chronic kidney disease (CKD). Symptoms and age at diagnosis of PH1 vary dramatically, from the most severe infantile forms leading to end-stage kidney disease (ESKD) during the first months of life to the less severe adult forms with moderate CKD and recurrent kidney stones. In 2020, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved a therapy based on RNA interference (RNAi) that profoundly reduces endogenous oxalate synthesis and dramatically changes the treatment algorithm for patients with PH1. The aim of this supplement of Clinical Kidney Journal includes contemporary reviews of the pathophysiology and genetics, (conventional) medical therapeutic management, urological therapeutic management and novel therapies (including not only RNAi, but also other therapeutic perspectives). The specific opinions of both adult and paediatric nephrologists will be compared and the ethical issues, as well as challenges faced by physicians and patients in developing countries, will also be discussed. Despite all the accomplishments, there are still looming questions that require further investigation and discovery.

Automated summary

This article reviews the significant progress in understanding and treating genetic primary hyperoxaluria, including the impact of gene mutations, medical therapy, and novel treatments. It also discusses the different perspectives of adult and pediatric nephrologists, as well as the challenges faced by physicians and patients in developing countries.