Abstract
BackgroundPrimary 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).CaseWe 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).ConclusionWe 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.
Highlights
Primary hyperoxaluria type 1 (PH1) is a multisystemic metabolic disorder caused by an excessive production of oxalate by the liver
Stiripentol has recently been reported as being effective in a PH1 cell culture model and in patients suffering from Dravet syndrome and PH1 [9]
Despite administering a dosage that is comparable with that administered to Dravet patients and the patient reported by Le Dudal et al, we were not able to demonstrate lowering of plasma oxalate concentrations (POx) concentrations
Summary
Primary hyperoxaluria type 1 (PH1) is one of the three genetically classified forms of inherited primary hyperoxalurias [1]. The patient had already received pyridoxine (9 mg/kg BW per day) for several months prior to admission as responsiveness to this medication has been described in patients with the Ile244Thr genotype [1] As his PD program has been insufficient to effectively lower POx concentration, we first introduced a daily program (10 dwells of 80 min with 300 mL each, Glc 1.5%; Ca2+ 1.25%) according to GPN standard. In addition to PD, we placed a tunneled catheter via the right vena jugularis interna and started our patient on continuous venovenous hemodiafiltration (CVVHDF, 5 sessions of 2–3 h per week; dialysate flow 57 L/h; blood flow 50–60 mL/min) Following initiation of this regimen, POx concentration dropped to 80.8 μmol/L (Fig. 1). POx concentrations were found to remain within the same range, suggesting that the withdrawal did not increase oxalate load further
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