Xortx Therapeutics announces publication on research of ADPKD

XORTX Therapeutics announces a research paper titled “Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models” has been accepted for publication in the peer-reviewed American Journal of Physiology-Renal Physiology and published online April 19, 2024. This study reports health consequences associated with increasing serum uric acid in mice or rat models of Autosomal Dominant Polycystic Kidney Disease, specifically the effects of increasing SUA on cyst growth and kidney size. Cyst genesis and cyst growth and their rates of change are important indicators of disease progression and are correlated with declining filtering capacity and end stage renal disease . This study shows, for the first time, that chronically increased SUA can significantly increase cyst index and increase kidney size in ADPKD. According to the study’s findings, saturating concentrations of SUA contributing to “crystal injury” were not necessary to negatively alter both structure and function of the ADPKD kidney. Moderately high SUA concentrations were also found to be associated with an increased inflammatory state in both serum and kidney tissue. Independent of the modifying effects of chronically increased SUA, a fundamental new discovery from this study was that over expression of xanthine oxidase in kidney tissue was present, suggesting aberrant purine metabolism may be present in ADPKD and suggesting a possible role of XO in disease progression. When considered together, SUA above the normal range and overexpression of XO, especially in the location of cysts, in an ADPKD kidney represents a strong impetus for the use of XO inhibition to attenuate this newly described mechanism of injury. Inhibition of XO using XORLO, XORTX’s proprietary formulation of oxypurinol, substantially lowered uric acid concentrations, attenuated the effects of chronically increased SUA on cyst index and kidney size in the RC/RC mouse model of ADPKD in this study.