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Oxalate homeostasis

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NATURE REVIEWS NEPHROLOGY
卷 19, 期 2, 页码 123-138

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NATURE PORTFOLIO
DOI: 10.1038/s41581-022-00643-3

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The maintenance of oxalate homeostasis is crucial for overall health, as disruptions in this balance can lead to kidney disease and cardiovascular complications. Recent studies have highlighted the importance of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion in maintaining oxalate homeostasis.
Oxalate homeostasis is maintained through a delicate balance between endogenous sources, exogenous supply and excretion from the body. Novel studies have shed light on the essential roles of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion to maintain oxalate homeostasis. In patients with primary or secondary hyperoxaluria, nephrolithiasis, acute or chronic oxalate nephropathy, or chronic kidney disease irrespective of aetiology, one or more of these elements are disrupted. The consequent impairment in oxalate homeostasis can trigger localized and systemic inflammation, progressive kidney disease and cardiovascular complications, including sudden cardiac death. Although kidney replacement therapy is the standard method for controlling elevated plasma oxalate concentrations in patients with kidney failure requiring dialysis, more research is needed to define effective elimination strategies at earlier stages of kidney disease. Beyond well-known interventions (such as dietary modifications), novel therapeutics (such as small interfering RNA gene silencers, recombinant oxalate-degrading enzymes and oxalate-degrading bacterial strains) hold promise to improve the outlook of patients with oxalate-related diseases. In addition, experimental evidence suggests that anti-inflammatory medications might represent another approach to mitigating or resolving oxalate-induced conditions. Disruptions in oxalate homeostasis can lead to kidney disease and cardiovascular complications. Here, the authors review the pathways that regulate oxalogenesis and the excretion of both exogenous and endogenous oxalate, consider the pathological effects of excess oxalate, and examine the latest therapeutic options for addressing oxalate dysregulation.

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