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

Abstract

Excessive excretion of oxalate in the urine results in the formation of calcium oxalate crystals and subsequent kidney stone formation. Severe forms of hyperoxaluria, including genetic forms and those that result from ethylene glycol poisoning, can result in end-stage renal disease. Therapeutic interventions are limited and often rely on dietary intervention. In this issue of the JCI, Le Dudal and colleagues demonstrate that the lactate dehydrogenase 5 inhibitor (LDH5) stiripentol reduces urinary oxalate excretion. Importantly, stiripentol treatment of a single individual with primary hyperoxaluria reduced the urinary oxalate excretion. Together, these results support further evaluation of LDH5 as a therapeutic target for hyperoxaluria.