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Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue
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Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue

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Lactate dehydrogenase 5: identification of a druggable target to reduce oxaluria

Jacob S Stevens, Qais Al-Awqati

    The Journal of Clinical Investigation
    |May 21, 2019
    PubMed

    Insights

    A new study shows stiripentol, a lactate dehydrogenase 5 inhibitor (LDH5), can reduce urinary oxalate excretion. This finding offers a potential new therapeutic target for hyperoxaluria, a condition leading to kidney stones.

    Area of Science:

    • Nephrology
    • Biochemistry
    • Metabolic Disorders

    Background:

    • Hyperoxaluria involves excessive urinary oxalate, leading to calcium oxalate crystals and kidney stones.
    • Severe hyperoxaluria, including genetic forms and ethylene glycol poisoning, can cause end-stage renal disease.
    • Current therapeutic options for hyperoxaluria are limited, primarily relying on dietary management.

    Purpose of the Study:

    • To investigate the effect of lactate dehydrogenase 5 (LDH5) inhibition on urinary oxalate excretion.
    • To evaluate stiripentol, an LDH5 inhibitor, as a potential therapeutic agent for hyperoxaluria.

    Main Methods:

    • The study by Le Dudal and colleagues investigated the impact of stiripentol on urinary oxalate levels.
    • A single patient with primary hyperoxaluria received stiripentol treatment.

    Main Results:

    • Stiripentol treatment was shown to reduce urinary oxalate excretion.
    • The treated individual with primary hyperoxaluria exhibited decreased urinary oxalate excretion.

    Conclusions:

    • Lactate dehydrogenase 5 (LDH5) inhibition is a promising therapeutic strategy for reducing urinary oxalate.
    • Stiripentol demonstrates potential as a novel treatment for hyperoxaluria and associated kidney stone formation.
    • Further research into LDH5 as a therapeutic target for hyperoxaluria is warranted.

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