Hyperoxaluria

Abstract

Three distinct types of primary hyperoxaluria (PH) have been identified based on molecular genetics and biochemical analyses. All types are characterized by loss of function of key enzymes of the hepatic glyoxylate metabolism. The prognosis of the disease is dependent on the type of PH. PH1 is the most common and the most severe form. Patients with PH1 have a high risk of progressing to end-stage kidney disease (ESKD) and of developing systemic manifestations related to oxalate depositions in tissues (systemic oxalosis). In comparison, PH2 carries an intermediate risk of kidney failure, usually in adulthood, and a lower risk of systemic oxalosis. PH3 is the most favorable form; ESKD has only been reported anecdotally in PH3, and, remarkably, symptomatic adults are rarely diagnosed. Measurement of urinary oxalate and genetic testing allow screening and rapid diagnosis of PH. Precise genotyping has important therapeutic implications. RNA interference treatment represents one of the first examples of precision medicine in nephrology. Nonetheless, hyperhydration and vitamin B6 (pyridoxine) supplementation in susceptible PH1 genotypes continue to represent the mainstay of treatment for many patients. However, effective and affordable treatment for PH remain an unmet need in many areas of the world. In addition to PH, hyperoxaluria can be secondary to intestinal malabsorption, to ingestion of oxalate precursors, or to specific dietary conditions. Without appropriate measures for prevention and treatment, secondary hyperoxaluria can cause severe kidney function impairment that may progress in some cases to ESKD.