Stiripentol fails to lower plasma oxalate in a dialysis-dependent PH1 patient

Pediatr Nephrol. 2020 Sep;35(9):1787-1789. doi: 10.1007/s00467-020-04585-5. Epub 2020 May 16.

Abstract

Background: Primary hyperoxaluria type 1 (PH1) is a multisystemic metabolic disorder caused by an excessive production of oxalate by the liver. The majority of patients presenting in early infancy have end-stage renal disease (ESRD). While awaiting the results of sRNAi trials, the current standard treatment is combined liver-kidney transplantation. Recently, Stiripentol has been reported as a promising drug in the treatment of primary hyperoxaluria by reducing urinary oxalate (UOx). Stiripentol is an anti-convulsive drug used in the treatment of children suffering from Dravet syndrome. It causes blockage of the last step in oxalate production by inhibition of hepatic lactate dehydrogenase 5 (LDH5).

Case: We administered Stiripentol as compassionate use in an anuric infant with dialysis-dependent PH1 over a period of 4 months. Although achieving plasma concentrations of Stiripentol that were recently reported to lower UOx excretion, we did not observe significant reduction to plasma oxalate concentrations (POx).

Conclusion: We conclude that Stiripentol may not be useful to reduce POx in PH patients with advanced chronic kidney disease (CKD), but larger studies are needed to confirm this finding.

Keywords: Dialysis; End-stage renal disease; Hyperoxaluria; Metabolic disorders; Stiripentol.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dioxolanes / administration & dosage*
  • Humans
  • Hyperoxaluria, Primary / drug therapy*
  • Infant
  • Male
  • Oxalates / blood

Substances

  • Dioxolanes
  • Oxalates
  • stiripentol

Supplementary concepts

  • Primary hyperoxaluria type 1