Treatment with stiripentol in a patient with primary hyperoxaluria type 1: lesson for the clinical nephrologist

Violier, Priscillia; Boyer, Olivia; Berthaud, Romain; Dorval, Guillaume

doi:10.1007/s40620-021-01116-9

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…One report of a patient with PH1 and good kidney function described a significant reduction in urine oxalate level after 10 weeks of treatment 112 . In another report of an 18-month-old patient with PH1 characterized by a pyridoxine-responsive mutation, administration of stiripentol led to a significant reduction in urinary oxalate level to normal values 113 . However, other case reports -albeit in patients with advanced kidney failure -found no benefit of stiripentol therapy 114,115 .…”

Section: Stiripentolmentioning

confidence: 95%

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

et al. 2023

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Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up. SectionsUnanswered questions and research agenda Conclusions

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Section: Stiripentolmentioning

confidence: 95%

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

et al. 2023

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“…UOx decreased from 1.24 to 0.07 mmol oxalate/ mmol creatinine. Clinically, evidence for nephro-calcinosis and kidney stone events were reduced [17 ▪ ]. However, in a separate case series of 3 PH1 patients with advanced CKD/kidney failure who were treated with stiripentol 50 mg/kg/day) for periods of 10–17 weeks, no change in POx or UOx was observed [33,34].…”

Section: Stiripentolmentioning

confidence: 97%

“…1), including Lumasiran (targeting GO) and nedosiran (targeting LDHa), have the greatest body of evidence to date [15,16 ▪▪ ]. Case series and studies also suggest possible benefit using the small molecule stiripentol (an anticonvulsant drug that targets LDHa) [17 ▪ ], lanthanum (an intestinal oxalate binding agent) [18 ▪ ], and Oxalobacter formigenes (an anaerobic gastrointestinal bacterium that degrades oxalate) [19 ▪ ]. Genetic editing tools including clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) have also been effective in animal PH1 models.…”

Section: Introductionmentioning

confidence: 99%

New therapeutics for primary hyperoxaluria type 1

Dejban

Lieske

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewPrimary hyperoxaluria type 1 (PH1) is a rare genetic disorder that causes hepatic overproduction of oxalate and, often, nephrocalcinosis, nephrolithiasis, chronic kidney disease, and kidney failure. The purpose of the review is to provide an update on current emerging therapies for the treatment of PH1.Recent findingsUse of ribonucleic acid interference (RNAi) therapeutics that target the liver to block production of key enzymes along pathways that generate oxalate is a promising approach. Available evidence supports the efficacy of both Lumasiran (targeting glycolate oxidase) and Nedosiran (targeting hepatic lactate dehydrogenase (LDHa)) to reduce urinary oxalate excretion in PH1. The efficacy of alternative approaches including stiripentol (an anticonvulsant drug that also targets LDHa), lanthanum (a potential gastrointestinal oxalate binder), and Oxalobacter formigenes (a bacterium that can degrade oxalate within the gastrointestinal tract and may also increase its secretion from blood) are all also under study. Genetic editing tools including clustered regularly interspaced short palindromic repeats/Cas9 are also in preclinical study as a potential PH1 therapeutic.SummaryNovel treatments can reduce the plasma oxalate concentration and urinary oxalate excretion in PH1 patients. Thus, it is possible these approaches will reduce the need for combined kidney and liver transplantation to significantly decrease the morbidity and mortality of affected patients.

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“…The team achieved notable success by administering Stiripentol to a 17-year-old girl with PH1 and her brother, who was also diagnosed with PH1 and underwent a CLKT, resulting in a significant reduction in UOx levels [132]. Stiripentol treatment also normalized the UOx:Cr levels and dissolved kidney stones in an 18-monthold child with PH1 [133]. Nevertheless, the compassionate therapeutic effects of Stiripentol in two PH1 patients, CKD (Patient 1) and ESRD (Patient 2), did not align with the results of the LDHA-RNAi study (NCT03392896), indicating an inadequate reduction in oxalate production in these individuals [134].…”

Section: Substrate Reduction Therapy (Srt)mentioning

confidence: 99%

Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs

Huang,

Zhu,

Zhou

et al. 2024

Biomolecules

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Primary hyperoxalurias (PHs) are inherited metabolic disorders marked by enzymatic cascade disruption, leading to excessive oxalate production that is subsequently excreted in the urine. Calcium oxalate deposition in the renal tubules and interstitium triggers renal injury, precipitating systemic oxalate build-up and subsequent secondary organ impairment. Recent explorations of novel therapeutic strategies have challenged and necessitated the reassessment of established management frameworks. The execution of diverse clinical trials across various medication classes has provided new insights and knowledge. With the evolution of PH treatments reaching a new milestone, prompt and accurate diagnosis is increasingly critical. Developing early, effective management and treatment plans is essential to improve the long-term quality of life for PH patients.

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Treatment with stiripentol in a patient with primary hyperoxaluria type 1: lesson for the clinical nephrologist

Cited by 7 publications

References 9 publications

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

New therapeutics for primary hyperoxaluria type 1

Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs

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