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

Kempf, Caroline; Pfau, Anja; Holle, Johannes; Müller-Schlüter, Karen; Bufler, Philip; Knauf, Felix; Müller, Dominik

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.