Kidney Week Educational Symposia-Emerging Paradigms in Primary Hyperoxaluria Type 1

Video Transcription

Video Summary

The session reviews primary hyperoxaluria type 1 (PH1), a rare metabolic liver disease caused by AGXT mutations leading to deficient or mistargeted hepatic alanine–glyoxylate aminotransferase (AGT). The resulting excess conversion of glyoxylate to oxalate causes hyperoxaluria, kidney stones, nephrocalcinosis, and progressive kidney failure; once renal function declines, systemic oxalate deposition (bone, vessels, heart, retina) can occur. Diagnosis relies on markedly increased urinary oxalate (and often glycolate), with plasma oxalate mainly useful in advanced CKD; genetic testing has replaced liver biopsy.<br /><br />Conservative management includes very high fluid intake, citrate, and pyridoxine (vitamin B6). B6 responsiveness—often linked to specific genotypes such as Gly170Arg and interactions with the “minor allele”—can reduce oxalate via improved AGT folding/targeting and activity, though outcomes vary widely even within families. Transplant strategies include preemptive liver transplant to correct the defect and combined liver–kidney transplant for ESRD; isolated kidney transplant is generally avoided but may be reasonable in fully B6-responsive patients.<br /><br />Emerging RNA interference “substrate reduction” therapies are highlighted: lumasiran (glycolate oxidase inhibition) shows large urinary oxalate reductions in PH1 with preserved kidney function; nedosiran (LDH inhibition) may help PH1. Oxalobacter trials were largely negative except possible benefit in dialysis. Speakers caution that long-term real-world effectiveness, access, and cost may limit replacing established paradigms.

Asset Subtitle

Moderators: Markus Kemper

Speakers:

Introduction - Markus Kemper
The Role of Genetics and Metabolism in PH1 Pathophysiology - Sonia Fargue
PH1 Clinical Trials and Therapeutics - Jaap Groothoff

Meta Tag

Date 11/6/2021

Pathway 1 Bone and Mineral Metabolism

Session ID 408416

Session Type ES - Educational Symposium

Keywords

Primary hyperoxaluria type 1 (PH1)

AGXT mutation

Alanine–glyoxylate aminotransferase (AGT) deficiency

Hyperoxaluria and oxalate nephropathy

Pyridoxine (vitamin B6) responsiveness

Liver–kidney transplantation

Lumasiran RNA interference therapy

Nedosiran LDH inhibition