hyperoxalurie

Hyperoxaluria is a condition characterized by abnormally high levels of oxalate excreted in the urine, which can promote the formation of calcium oxalate kidney stones and nephrocalcinosis. It is usually categorized as primary or secondary.

Primary hyperoxaluria refers to inherited disorders that cause overproduction of oxalate in the liver. The best described forms are type 1, due to defects in the AGXT gene encoding alanine-glyoxylate aminotransferase; type 2, due to GRHPR gene mutations; and type 3, due to HOGA1 gene mutations. A fourth form has been described in association with mutations in an oxalate transporter gene. Primary hyperoxalurias often present in childhood or early adulthood and may progress to kidney failure if not treated. Secondary, or enteric, hyperoxaluria results from increased intestinal absorption of oxalate in the setting of fat malabsorption or after certain surgeries (for example, extensive bowel resection or bariatric procedures). Dietary oxalate intake contributes but is usually not the sole cause of severe disease.

Pathophysiology involves oxalate binding calcium to form calcium oxalate crystals, which can accumulate in the kidneys, leading to stones, nephrocalcinosis, and decline in renal function. Decreased urine volume and changes in gut calcium binding can worsen crystallization.

Diagnosis relies on measurements of 24-hour urinary oxalate excretion, urinary oxalate-to-creatinine ratios, and stone analysis, with genetic testing to confirm primary forms and evaluation of underlying fat malabsorption for secondary forms. Plasma oxalate may be elevated in advanced disease.

Treatment focuses on reducing oxalate burden and preventing stones: high fluid intake, citrate to inhibit crystallization, and diet modification; pyridoxine responsiveness may occur in some PH1 patients; management of secondary hyperoxaluria targets the underlying malabsorption. In progressive PH1, liver transplantation (with kidney transplantation in some cases) can be curative.