Investigational Therapies for Primary Hyperoxaluria

Kletzmayr, Anna; Ivarsson, Mattias E.; Leroux, Jean‐Christophe

doi:10.1021/acs.bioconjchem.0c00268

Cited by 19 publications

(22 citation statements)

References 86 publications

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“…While orthotopic liver transplantation is the only definitive cure for PH [ 50 ], numerous potential therapies for primary and enteric hyperoxalurias are currently being studied [ 69 ]. One approach to PH therapy involves downregulation of key enzymes, glycolate oxidase and lactate dehydrogenase, in the oxalate metabolism pathway through gene silencing methods [ 70 , 71 , 72 , 73 ] or enzyme inhibition [ 74 ].…”

Section: Resultsmentioning

confidence: 99%

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Dietary Oxalate Intake and Kidney Outcomes

et al. 2020

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Oxalate is both a plant-derived molecule and a terminal toxic metabolite with no known physiological function in humans. It is predominantly eliminated by the kidneys through glomerular filtration and tubular secretion. Regardless of the cause, the increased load of dietary oxalate presented to the kidneys has been linked to different kidney-related conditions and injuries, including calcium oxalate nephrolithiasis, acute and chronic kidney disease. In this paper, we review the current literature on the association between dietary oxalate intake and kidney outcomes.

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Section: Resultsmentioning

confidence: 99%

“…For enteric hyperoxaluria, oral administration of oxalate decarboxylase is currently being studied by two pharmaceutical companies with promising results [ 78 ] ( ). An in-depth review of novel investigational therapies for the hyperoxalurias was recently published by Kletzmayr et al [ 69 ].…”

Section: Resultsmentioning

confidence: 99%

Dietary Oxalate Intake and Kidney Outcomes

et al. 2020

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“…Major progress has been made towards potential treatment of hyperoxaluric patients (Burns et al, 2020;Este `ve et al, 2019;Kletzmayr et al, 2020;Le Dudal et al, 2019;Liebow et al, 2017). These new molecules call for solid follow-up markers and surrogate endpoint (Milliner et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Detection and localization of calcium oxalate in kidney using synchrotron deep ultraviolet fluorescence microscopy

Estève¹,

Buob²,

Jamme³

et al. 2022

J Synchrotron Radiat

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Renal oxalosis is a rare cause of renal failure whose diagnosis can be challenging. Synchrotron deep ultraviolet (UV) fluorescence was assayed to improve oxalosis detection on kidney biopsies spatial resolution and sensitivity compared with the Fourier transform infrared microspectroscopy gold standard. The fluorescence spectrum of synthetic mono-, di- and tri-hydrated calcium oxalate was investigated using a microspectrometer coupled to the synchrotron UV beamline DISCO, Synchrotron SOLEIL, France. The obtained spectra were used to detect oxalocalcic crystals in a case control study of 42 human kidney biopsies including 19 renal oxalosis due to primary (PHO, n = 11) and secondary hyperoxaluria (SHO, n = 8), seven samples from PHO patients who received combined kidney and liver transplants, and 16 controls. For all oxalocalcic hydrates samples, a fluorescence signal is detected at 420 nm. These spectra were used to identify standard oxalocalcic crystals in patients with PHO or SHO. They also revealed micrometric crystallites as well as non-aggregated oxalate accumulation in tubular cells. A nine-points histological score was established for the diagnosis of renal oxalosis with 100% specificity (76–100) and a 73% sensitivity (43–90). Oxalate tubular accumulation and higher histological score were correlated to lower estimated glomerular filtration rate and higher urinary oxalate over creatinine ratio.

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“…Lumasiran reduces glycolate oxidase (GO) by degrading the mRNA-encoding GO (Figure 1 ). The reduction in GO results in a decline in liver-produced oxalates [ 4 , 5 ]. A double-blinded randomized trial in PH1 patients aged six years or older has demonstrated a 53.5% reduction in 24-hour urinary oxalate excretion and a substantial decrease in plasma oxalate levels [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Infantile Primary Hyperoxaluria Type 1 Treated With Lumasiran in Twin Males

Aldabek¹,

Grossman²,

Alomar³

et al. 2022

Cureus

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Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that results in oxalate overproduction leading to nephrolithiasis (NL), nephrocalcinosis (NC), kidney failure, and systemic oxalosis. Infantile PH1 is its most severe form, and it may require intensive hemodialysis followed by a liver-kidney transplant. Lumasiran is an RNA interference (RNAi) therapeutic agent that reduces hepatic oxalate production, which has been recently approved for the treatment of PH1. In this report, we present a case of twin males with infantile PH1 and bilateral NL and NC who were treated with lumasiran at 12 months of age. Their symptoms abated after therapy was started without disease progression. To the best of our knowledge, this is the first report of PH1 occurring in twins and the first report on using lumasiran to treat infantile PH1 outside of a clinical trial. Lumasiran appears to be a successful therapeutic option for infantile PH1.

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Investigational Therapies for Primary Hyperoxaluria

Cited by 19 publications

References 86 publications

Dietary Oxalate Intake and Kidney Outcomes

Dietary Oxalate Intake and Kidney Outcomes

Detection and localization of calcium oxalate in kidney using synchrotron deep ultraviolet fluorescence microscopy

Infantile Primary Hyperoxaluria Type 1 Treated With Lumasiran in Twin Males

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