excess oxalic acid or oxalates in the urine, often causing kidney stones
Primary hyperoxaluria is a monogenic rare liver disease that causes the liver to produce excessive levels of endogenous oxalate as a metabolic end product. Consequently, oxalate builds up in the urine, causing recurrent kidney stone formation, renal damage, kidney failure, and even systemic oxalosis and death. There are three types of primary hyperoxaluria (PH1, PH2, and PH3), each associated with a specific metabolic defect. PH1 is the most common type, affecting roughly 80% of all cases, and most severely affects children. There are currently no effective therapies for primary hyperoxaluria. The only comprehensive treatment option is a liver transplant (often complicated for young children), or a liver-kidney double transplant once the kidneys have failed.
Secondary hyperoxaluria, unlike primary hyperoxaluria, is mainly caused by high absorption of dietary oxalate. Over absorption of oxalate by the gastrointestinal system can be due to an underlying GI issue/disruption (also known as enteric hyperoxaluria), or can be idiopathic. Similar to PH, secondary hyperoxaluria causes recurrent calcium oxalate kidney stone formation and over time, compounding damage to the renal system. Significant contributors to enteric hyperoxaluria include irritable bowel disease, malabsorptive bariatric surgery (developing in over 50% of the patients) and obesity (often associated with mild to moderate hyperoxaluria). In either the primary or secondary hyperoxaluria condition, no therapies exist to reduce urinary oxalate excretion. Current standard-of-care centers around lifestyle changes by increasing water consumption and decreasing the consumption of high-oxalate foods. These changes are often impracticable for many professional and frustrating to adhere to, and importantly, insufficient for the most severe cases of hyperoxaluria.
Excessive amounts of oxalate molecules in the plasma
Approximately 30M Americans have chronic kidney disease (CKD). Plasma oxalate significantly rises to levels that can exceed 30 µM as kidney function declines, putting a significant number of patients with CKD at risk for calcium oxalate (CaOx) supersaturation in plasma. CaOx supersaturation increases risk for inflammasome-induced systemic inflammation and adverse cardiovascular outcomes, as well as abnormally high proximal tubular oxalate secretion leading to CaOx crystal-induced renal inflammation and contribution to CKD progression. Emerging data show that ESRD-associated hyperoxalemia might contribute to the high cardiovascular risk in this patient population. Therefore, lowering serum oxalate could improve cardiovascular outcomes in CKD and ESRD patients as well as slow CKD progression. Hyperoxalemia is seen in PH patients are renal functions of these patients quickly decrease.