• Chronically Increased Uric Acid Accelerates Structural
and Functional Changes in Polycystic Kidney Disease •
The abstract presents the findings of studies conducted at the
- Total kidney / body weight ratio – indicating the possibility of accelerated formation or growth of cysts and represents a measure analogous to total kidney volume measures in humans with PKD;
- Creatinine, supporting the concept of a decrease in filtering capacity of kidneys; and
- Cyst index is increased, suggesting uric acid may act to specifically accelerate disease progression in PKD.
In summary, increasing serum uric acid by inhibiting uricase with oxonic acid (“OXO”) results in an increase in kidney weight, cyst index, creatinine in PCK rat and RC mouse models of PKD. Further characterization of potential mechanisms of injury, including increased cyst growth that will be investigated include crystal deposition causing tubular dilatation, increased reactive oxygen radicals and pro-inflammatory cytokines/chemokines causing tubular cell proliferation and endothelial injury are ongoing.
About this study
Unlike most forms of life, humans lack an active uricase enzyme that converts uric acid to allantoin. In rodents, uricase converts uric acid to allantoin and uricase inhibition raises serum uric acid. The aim of this study was to determine whether raising serum uric acid with OXO was associated with worse PKD.
Dr.
About the
ASN represents more than 21,000 kidney health professionals working to help people with kidney diseases and their families. Source: https://www.asn-online.org/.
The Kidney Week program and abstracts are available on the ASN website.
About ADPKD
ADPKD is a rare disease that affects more that 10 million individuals worldwide.1,2 ADPKD is typically diagnosed based upon expansion of fluid-filled cysts in the kidneys. Over time, the increasing number and size of cysts can contribute to structural and functional changes to kidneys and is frequently accompanied by chronic pain which is a common problem for patients with ADPKD.3 Expansion of cysts is thought to compress healthy functioning tissue surrounding the cysts and contribute to further loss of kidney function, fibrosis, impaired nutrient exchange and impaired kidney function, accompanied later by end-stage renal disease.1 Health consequences of high uric acid have been reported to be increased in ADPKD individuals, including increased incidence of kidney stones5 and gout.6,7 For individuals with progressing ADPKD, treatment recommendations include anti-hypertensive treatment, dietary restrictions, and, for a limited percentage of suitable patients, pharmacotherapy.4 New, more broadly applicable therapies to effectively slow decline of kidney function in ADPKD are needed.
About
XORTX is a pharmaceutical company with two clinically advanced products in development: 1) our lead, XRx-008 program for ADPKD; and 2) our secondary program in XRx-101 for acute kidney and other acute organ injury associated with Coronavirus / COVID-19 infection. In addition, XRx-225 is a pre-clinical stage program for Type 2 Diabetic Nephropathy. 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. At XORTX, we are dedicated to developing medications to improve the quality of life and future health of patients. Additional information on XORTX is available at www.xortx.com.
For further information, please contact:
adavidoff@xortx.com or +1 403 455 7727 | nick@alpineequityadv.com or +1 617 901 0785 |
Neither the
References:
- Wiley C., Kamat S., Stelhorn R., Blais J., Analysis of nationwide date to determine the incidence and diagnosis of autosomal dominant polycystic kidney disease in the
USA , Kidney Disease, 5(2): 107-117, 2019 - Bergmann C.,
Guay-Woodford L.M .,Harris P.C. , Horie S., Peters D.J., Torres V.E., Polycystic Kidney Disease, Nat Rev Dis Primers. 4(1): 50, 2018 - https://pkdcure.org/living-with-pkd/chronic-pain-management
- Gimpel C., Bermann C., Bockenhauer D., et al., International consensus statement of the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people, Nat Rev Nephrol 15(11):713-726, 2019
- Torres VE, et al,
The Association of Nephrolithiasis and Autosomal Dominant Polycystic Kidney Disease , Am J Kidney Dis, 1988, vol 11, 318-325 - Newcombe, DS. Letter Gouty Arthritis and polycystic kidney disease, Ann Intern Med, 1973 vol 79, pg 605
- Rivera JV Martinez, et al, Association of hyperuricemia and polycystic kidney disease, Bol Asoc Med P R, 1965 vol 7 251-263
Forward Looking Statements
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