Primary hyperoxalurias are rare autosomal recessive inherited disorders characterized by hepatic overproduction of endogenous oxalate, which can lead to recurrent calcium oxalate kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. There are three known types of primary hyperoxaluria. Primary hyperoxaluria type 1 is caused by mutations in AGXT, resulting in deficiency of alanine-glyoxylate aminotransferase leading to impaired conversion of glyoxylate to glycine and subsequent increased conversion of glyoxylate to oxalate. Primary hyperoxaluria type 2 is caused by mutations in GRHPR, resulting in deficiency of glyoxylate reductase/hydroxypyruvate reductase. Primary hyperoxaluria type 3 is caused by mutations in HOGA1, resulting in deficiency of 4-hydroxy-2-oxoglutarate (HOG) aldolase. Although clinical manifestations overlap among the 3 types, disease severity is typically greatest in primary hyperoxaluria type 1. Early diagnosis has important implications for disease progression and management, particularly with the availability of targeted therapies for primary hyperoxaluria type 1. Urinary oxalate is routinely measured as part of the 24-hour urine collection for metabolic evaluation, with a commonly used upper limit of normal being 0.46 mmol/24 hour, or approximately 40 mg/day, although reference ranges may vary by laboratory. In pediatric patients, 24-hour urinary oxalate excretion should be normalized to 1.73 m² body surface area. When a timed urine collection is not feasible, a random urine oxalate-to-creatinine ratio may be used, provided age-specific reference ranges are applied. For both adult and pediatric patients, values above the upper reference limit should be confirmed with repeat testing. Hyperoxaluria may result from secondary causes, including excessive dietary oxalate or vitamin C intake, enteric hyperoxaluria from intestinal malabsorption or prior intestinal surgery (discussed further in Statement 17), and parenteral nutrition, or it may reflect primary hyperoxaluria types 1, 2, or 3.122 No single cutoff for urinary oxalate is diagnostic for primary hyperoxaluria. Urinary oxalate excretion >0.7 mmol/1.73 m²/24 hour or a urine oxalate-to-creatinine ratio above the age-specific reference range should prompt further evaluation for primary hyperoxaluria when secondary causes are not identified.123 Urinary oxalate excretion >1.0 mmol/1.73 m²/24 hour is strongly suggestive of primary hyperoxaluria after exclusion of enteric and other secondary causes.124 The prior AUA Guideline cutoff of >75 mg/day in adults without bowel dysfunction may be considered a general threshold for suspecting primary hyperoxaluria, but is not diagnostic.24 Urinary oxalate may be less reliable in patients with advanced CKD and plasma oxalate testing, and specialist referral should be considered. Definitive diagnosis of primary hyperoxaluria requires genetic testing. Genetic testing facilitates timely and precise diagnosis of primary hyperoxaluria and can distinguish among the three known types. Testing may be performed using commercially available panels. Identification of pathogenic AGXT variants in patients with primary hyperoxaluria type 1 may help identify those more likely to respond to pyridoxine therapy and guide treatment decisions.125 Genetic counseling, referral to centers with expertise in inherited stone disease, and consultation with expert clinicians can help facilitate diagnostic interpretation, patient and family counseling, and treatment planning.126