Afi Dumenya

Microbiome-derived Peptides with Therapeutic Potential for Hyperoxalemia, Hyperoxaluria, and Related Kidney Stones

Kidney stone disease (KSD) is the second most prevalent kidney disease in the United States. There are two outlets of kidney stone formation that increase the risk of kidney stone which includes hyperoxalemia (high plasma oxalate) and hyperoxaluria (high urine oxalate). It’s difficult to limit oxalate levels since it’s very common in foods and beverages, and produced by the liver. No drug addresses both hyperoxalemia and hyperoxaluria except FDA-approved Exlumo which only targets urine oxalate. Oxalobacter formigenes (OF) is a bacterium that plays a role in oxalate homeostasis. The lab discovered that OF-derived secreted factors significantly stimulate oxalate transport in human intestinal cells in vitro and reduce urinary oxalate excretion in hyperoxaluric mice with the peptides P8 and P9 identified as the major secreted factors. The peptides have a short half-life so structural modification is needed to enhance the therapeutic potential. Our current study focuses on evaluating the therapeutic effects of different modifications of the P8 and/or P9 and/or novel peptides to find an optimal dose to be used in vivo. Our study is still ongoing so there is no evaluation of these results. To ensure that data was collected, the main responsibilities that were maintained included breeding cage and metabolic cage maintenance. Our main goal is to improve the efficiency of the oral nanoparticles to optimally reduce oxalate levels.