AI Article Synopsis

  • Excessive endogenous oxalate synthesis can lead to kidney stones and renal failure, with hydroxyproline metabolism being a key contributor.
  • Researchers infused different mouse models with labeled hydroxyproline to measure its role in urinary oxalate excretion, finding that Agxt KO mice produced significantly more oxalate than wild-type mice.
  • SiRNA targeting specific liver enzymes successfully reduced enzyme expression and urinary oxalate levels in Agxt KO mice, suggesting a potential treatment strategy for reducing kidney oxalate load in Primary Hyperoxaluria patients.

Article Abstract

Excessive endogenous oxalate synthesis can result in calcium oxalate kidney stone formation and renal failure. Hydroxyproline catabolism in the liver and kidney contributes to endogenous oxalate production in mammals. To quantify this contribution we have infused Wt mice, Agxt KO mice deficient in liver alanine:glyoxylate aminotransferase, and Grhpr KO mice deficient in glyoxylate reductase, with (13)C5-hydroxyproline. The contribution of hydroxyproline metabolism to urinary oxalate excretion in Wt mice was 22±2%, 42±8% in Agxt KO mice, and 36%±9% in Grhpr KO mice. To determine if blocking steps in hydroxyproline and glycolate metabolism would decrease urinary oxalate excretion, mice were injected with siRNA targeting the liver enzymes glycolate oxidase and hydroxyproline dehydrogenase. These siRNAs decreased the expression of both enzymes and reduced urinary oxalate excretion in Agxt KO mice, when compared to mice infused with a luciferase control preparation. These results suggest that siRNA approaches could be useful for decreasing the oxalate burden on the kidney in individuals with Primary Hyperoxaluria.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706777PMC
http://dx.doi.org/10.1016/j.bbadis.2015.12.001DOI Listing

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