Primary hyperoxaluria type 1: time for prime time?

Area of Science:

• Nephrology
• Genetics
• Biochemistry

Background:

• Primary hyperoxaluria type 1 (PH1) is an autosomal recessive genetic disorder caused by mutations in the AGXT gene.
• This leads to deficient alanine-glyoxylate aminotransferase (AGT) activity, resulting in excess oxalate production, kidney stones, nephrocalcinosis, and chronic kidney disease (CKD).
• Disease presentation varies widely, from severe infantile forms causing end-stage kidney disease (ESKD) to milder adult forms with recurrent stones and moderate CKD.

Discussion:

• The 2020 FDA and EMA approval of RNA interference (RNAi) therapy marks a paradigm shift in PH1 management.
• This supplement reviews current knowledge on PH1 pathophysiology, genetics, conventional medical and urological treatments, and novel therapeutic strategies.
• It also compares pediatric and adult nephrologists' perspectives, discusses ethical considerations, and addresses challenges in developing countries.

Key Insights:

• RNAi therapy offers a profound reduction in endogenous oxalate synthesis for PH1 patients.
• Understanding the genetic basis and varied clinical spectrum of PH1 is crucial for timely diagnosis and management.
• Multifaceted approaches, including novel therapies, are essential to improve long-term outcomes.

Outlook:

• Further research is needed to address remaining questions in PH1 management.
• Continued investigation into emerging therapies beyond RNAi holds promise for future treatment advancements.
• Addressing global disparities in healthcare access is vital for equitable PH1 patient care.