hyperoxaluria

Hyperoxaluria is a condition characterized by excessive excretion of oxalate in the urine. Persistent hyperoxaluria can lead to calcium oxalate kidney stones, nephrocalcinosis, and progressive kidney dysfunction. It may arise as a genetic disorder (primary hyperoxaluria) or as a consequence of underlying diseases or dietary factors (secondary hyperoxaluria).

Primary hyperoxaluria comprises several rare autosomal recessive disorders caused by defects in hepatic enzymes that metabolize glyoxylate, most commonly type I (AGXT), type II (GRHPR), and type III (HOGA1). Secondary hyperoxaluria results from excessive intestinal oxalate absorption or intake, such as fat malabsorption, inflammatory bowel disease, bariatric surgery, or high dietary oxalate and vitamin C.

Pathophysiology involves oxalate combining with calcium to form crystals that damage renal tubules. Factors that promote stone formation include low urine volume, chronic dehydration, and high urinary oxalate. Symptoms range from nephrolithiasis with flank pain and hematuria to recurrent infections or gradual loss of kidney function in advanced disease; rare extrarenal oxalate deposition can occur.

Diagnosis relies on elevated 24-hour urinary oxalate excretion, with thresholds typically above about 40–45 mg/day in adults. Plasma oxalate may be elevated in advanced disease. Confirmation of primary hyperoxaluria requires genetic testing or enzymatic assays; imaging may show nephrocalcinosis or stones; stone analysis can reveal calcium oxalate crystals.

Management emphasizes high fluid intake and dietary measures to reduce oxalate absorption, with calcium or magnesium salts taken with meals to bind oxalate. Vitamin B6 (pyridoxine) improves oxalate metabolism in some PH1 patients; Lumasiran, an RNA interference therapy, reduces hepatic oxalate production in PH1. Severe PH1 may require liver transplantation or combined liver-kidney transplantation; management of secondary hyperoxaluria targets the underlying condition.