Adenine promotes renal calcium oxalate crystallization involving disruption of the intestinal barrier and altered SLC26A3 and SLC26A6 expression.

Recent studies have demonstrated that intestinal metabolites play a critical role in the pathogenesis of calcium oxalate (CaOx) nephrolithiasis; however, the underlying mechanisms remain largely elusive. In this study, we found that rats with renal CaOx crystallization exhibited distinct intestinal metabolite profiles, characterized by the enrichment of purine metabolism and a marked increase in adenine levels. Further experiments confirmed that adenine significantly promotes CaOx crystal deposition in both rat and Drosophila models. Mechanistically, adenine disrupts intestinal architecture, downregulates the expression of barrier-related tight junction proteins, and dysregulates intestinal oxalate transporters (SLC26A3 and SLC26A6), which is associated with increased net enteric oxalate absorption. Collectively, these findings suggest that adenine may enhance intestinal oxalate absorption while reducing excretion, ultimately contributing to hyperoxaluria and promoting renal CaOx crystallization. These findings reveal a previously unrecognized role of adenine in the pathogenesis of CaOx nephrolithiasis and highlight potential therapeutic targets for intervention.