Oxalate Nephropathy and the Mechanism of Oxalate-Induced Kidney Injury.

Abstract

Background: Hyperoxaluria is a major cause of oxalate nephropathy, which can lead to impaired renal function presenting as acute kidney injury, acute on chronic kidney disease, or chronic kidney disease. The Chronic Renal Insufficiency Cohort study showed that higher urinary oxalate is associated with renal outcome in patients with chronic kidney disease, supporting the nephrotoxicity of oxalate. Therefore, a better understanding of the role of oxalate in kidney injury is needed. This review describes the metabolism of oxalate and the clinical and pathology presentation of oxalate nephropathy. It also summarizes the available evidence for the underlying pathogenic mechanism and the development of treatments for oxalate-induced kidney injury.

Summary: Disruption to any key step in the oxalate pathway including abnormal endogenous generation, ingestion of abnormally high dose of oxalate, increased absorption or attenuation of oxalate degradation in the gut, and reduced excretion through the kidney may lead to disrupted oxalate homeostasis. Oxalate nephropathy is mainly caused by hyperoxaluria. Oxalate crystal deposition in the kidney is usually accompanied with tubular toxicity, obstruction, interstitial fibrosis, and tubular atrophy. The mechanism of oxalate-induced renal injury has not been fully clarified. Evidence from both in vivo and in vitro studies shows that NLRP3 inflammasome activation and macrophage infiltration are involved in the processes of crystal adhesion, aggregation, and elimination and promote intrarenal inflammation and renal fibrosis. Novel treatment strategies have been developed and targeted therapies tested for oxalate nephropathy.

Key messages: Prompt diagnosis and management may help to reduce the deposition of calcium oxalate crystals in the kidney. Further studies are needed to clarify the underlying mechanisms to help develop more targeted therapies for oxalate nephropathy.