The Abstract"Raising Serum Uric Acid with a Uricase Inhibitor Worsens PKD in Rat and Mouse models" will be presented during the Session Title: Genetic Diseases of the Kidneys, by Dr. Charles Edelstein of the University of Colorado and Dr. Allen Davidoff, CEO of XORTX. (menafn.com)
Recent studies have reported that mild hyperuricemia in normal rats induced by the uricase inhibitor, oxonic acid (OA), results in hypertension, intrarenal vascular disease, and renal injury. (scienceopen.com)
The title of the poster presentation selected by the Kidney Week Education Committee and following peer review is "Raising Serum Uric Acid with a Uricase Inhibitor Worsens PKD in Rat and Mouse Models " which will be presented during the ASN Session Title: Genetic Diseases of the Kidneys, by Dr. Charles Edelstein of the University of Colorado. (xortx.com)
In summary, increasing serum uric acid by inhibiting uricase with oxonic acid ("OXO") results in an increase in kidney weight, and decreased kidney function in rodent models of PKD. (menafn.com)
The results of this study show that increased serum uric acid can accelerate injury in two separate models of PKD and importantly reports fundamental findings in support of the Company's XRx-008 program. (menafn.com)
The aim of this study was to determine whether raising serum uric acid with OXO was associated with worse PKD. (menafn.com)
Most importantly, results of this study show that increased serum uric acid can accelerate injury in two separate models of PKD in different species - a fundamental finding that we believe supports the XRx-008 program. (xortx.com)
ABSTRACT: Epidemiological and clinical studies showed an association between an increase in serum uric acid (SUA), hypertension (HT) and kidney damage. (ipn.mx)
Converts uric acid to allantoin3
Despite these promising data, we noticed that the plasma uric acid (UA) levels in most studies were normal or even low because of the degradation of uricase, an enzyme that converts uric acid to allantoin, which is much more soluble than uric acid [ 10 ]. (hindawi.com)
Unlike most forms of life, humans lack an active uricase enzyme that converts uric acid to allantoin. (menafn.com)
Humans are predisposed to chronically high uric acid and gout because they lack uricase that converts uric acid to allantoin. (xortx.com)
High circulati1
This presentation will report for the first time, that XORTX's XRx-008 formulation of Xanthine Oxidase inhibitor can substantially and significantly block the increase in kidney size associated with high circulating uric acid in a rodent model of polycystic kidney disease. (menafn.com)
Uric acid levels3
Allopurinol significantly reduced uric acid levels and blocked the renal functional and histologic changes. (scienceopen.com)
Benziodarone reduced uric acid levels less effectively and only partially improved BP and renal function, with minimal effect on the vascular changes. (scienceopen.com)
CSA-OA treated rats had higher uric acid levels in association with more severe arteriolar hyalinosis and tubulointerstitial damage. (ewha.ac.kr)
Enzyme2
XO is an enzyme that generates ROS by catalyzing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. (hindawi.com)
The effect of hyperuricemia on CSA nephropathy was determined by blocking the hepatic enzyme uricase with oxonic acid (CSA-OA). (ewha.ac.kr)
Intrarenal1
The mechanism does not involve intrarenal uric acid crystal deposition and appears to involve activation of the renin angiotensin system and inhibition of intrarenal nitric oxide production. (ewha.ac.kr)
Chronically1
The abstract presents new discoveries in two species - mouse and rat models of polycystic kidney disease ("PKD") and reports original work showing the harmful consequence of chronically increased uric acid on both structure and function of kidneys. (menafn.com)
Rats2
Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were also significantly increased in these rats. (hindawi.com)
Control groups included rats treated with vehicle (VEH) and oxonic acid alone (OA). (ewha.ac.kr)
This led to the hypothesis that uric acid may contribute to progressive renal disease. (scienceopen.com)
Experimentally, moderate hyperuricaemia by oxonic acid (OA) produces, HT, renal vascular lesions and accelerates the progression of renal disease, independent of the deposit of urate crystals. (ipn.mx)
Xanthine1
XORTX is working to advance its clinical development stage products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. (xortx.com)
Vascular4
Given observations that uric acid induces vascular disease, the effect of uric acid on vascular smooth muscle cells in culture was also examined. (scienceopen.com)
In in vitro studies, cultured vascular smooth muscle cells incubated with uric acid also generated COX-2 with time-dependent proliferation, which was prevented by either a COX-2 or TXA-2 receptor inhibitor. (scienceopen.com)
El daño vascular por hiperuricemia se asoció con HT sistémica y glomerular en los animales normales, la administración de Alo evitó estas anomalías. (ipn.mx)
Adicionalmente, durante daño renal crónico, la marcada disminución del lumen vascular inducido por hipertrofia vascular severa resulta en isquemia renal que contribuye a acelerar la progresión de la enfermedad renal. (ipn.mx)
Kidney1
1 Health consequences of high uric acid have been reported to be increased in ADPKD individuals, including increased incidence of kidney stones 5 and gout. (xortx.com)
Increase2
An increase in uric acid exacerbates CSA nephropathy in the rat. (ewha.ac.kr)
An increase in membrane damage, measured by monitoring the formation of thiobarbituric acid-reactive substances (TBARS) and lactic dehydrogenase (LDH) release, was observed only in sperm treated with H(2)O(2), ADP and FeSO(4). (propoleo.cl)
Increasing evidence suggests favorable effect of serum uric acid (UA) on bone metabolism due to its antioxidant properties. (dovepress.com)
Administration1
To answer the question if asymptomatic HrU in the context of salt sensitivity (SS) is a friend or foe, we explored conditions of induced mild HrU & a high salt diet on the development of HTN using Dahl SS rats & administration of either oxonic acid, a uricase inhibitor that prevents the breakdown of UA further into more soluble allantoin &/or probenecid, an inhibitor of the UA transporter Urat1, preventing UA reuptake. (asn-online.org)
Effect1
This mild HrU was associated with attenuated progression of SS HTN while probenecid did not affect MAP & diminished the effect of oxonic acid (MAP for control & treatment 1-3 groups: 156±3, 138±3 , 162±3, & 154±4 mmHg). (asn-online.org)
Damage1
An increase in membrane damage, measured by monitoring the formation of thiobarbituric acid-reactive substances (TBARS) and lactic dehydrogenase (LDH) release, was observed only in sperm treated with H(2)O(2), ADP and FeSO(4). (propoleo.cl)