Compositions and methods for diagnosis, treatment of and prevention of kidney disease
OwnerAllen DAVIDOFFinventor
Life of this patent
Estimating the term…
Loading patent…
OwnerAllen DAVIDOFFinventor
Estimating the term…
Disclosed herein are methods of detecting xanthine oxidase expression in polycystic kidney disease, or methods of delaying the onset or treating polycystic kidney disease, or both. The inventors have made the remarkable discovery that aberrant purine metabolism is not a corollary to disease but rather tissue expression of xanthine oxidase/xanthine dehydrogenase (XO/XDH) expression is increased and possibly uric acid and oxygen radical production acting alone or in combination acts as a primary mediator of progression of structural and functional dysfunction. Specifically exemplified are methods that involve, measuring and evaluating tissue XO/XDH expression in polycystic kidney disease or any cystic tissue. Moreover, specifically exemplified are methods that involve administering to a patient susceptible to development of polycystic kidney disease a composition of agents, including uric acid lowering agents in a regimen that decreases expression of XO/XDH, lowering intracellular uric acid or free oxygen radical expression in a tissue.
A method of detecting and treating kidney disease progression in a subject, the method comprising
The method of any of claims 1-5, wherein the sample is blood, urine or both and the detecting comprises detecting antigens associated with XO or XDH or both, or amino acid chain fragments of XO or XDH. 7, The method of any of claims 1-6, wherein the xanthine oxidase inhibitor comprises oxypurinol. 8 The method of claim 7, wherein the composition further comprises an organic base, wherein the organic base is optionally one or more of L-arginine, D-arginine, choline, L-lysine, D-lysine, caffeine, biguanide, biguanidine or gliflozin.
The method of claim 7, further comprising co-administering a therapeutically effective amount of an organic base.
A method comprising detecting changes to xanthine oxidase (XO) concentration or activity or xanthine dehydrogenate (XDH) concentration or activity, or the XO/XDH ratio of concentration or activity, the method comprising
A method of reducing aberrant purine metabolism associated with kidney disease in a subject in need, the method comprising administering a therapeutically effective amount of one or more uric acid lowering agents, wherein the method treats a symptom of cystic disease, and wherein the one or more uric acid lowering agents are optionally selected from the group consisting of xanthine oxidase inhibitor and sirtuin-1 activator.
A method of reducing markers of kidney disease progression in a subject, the method comprising obtaining a sample from a subject;
A method comprising detecting presence of a marker, or a ratio of markers in a biological sample from a subject;
A method comprising administering a therapeutically effective amount of a uric acid lowering agent to a subject exhibiting elevated xanthine oxidase activity or concentration relative to that of a healthy subject, or a XO/XDH concentration or activity ratio that deviates from that of a healthy subject, in a urine sample of the subject.
A method of monitoring effectiveness of a treatment of polycystic kidney disease comprising
A composition comprising an amount of a oxypurinol and an amount of metformin, and/or an SGLT2 Inhibitor.
A method of treating polycystic kidney disease that comprises co-administering therapeutically effective amounts of xanthine oxide inhibitor and metformin.
A composition comprising a therapeutically effective amount of a uric acid lowering agent and a therapeutically effective amount of tolvaptan and/or lixivaptan.
A method of treating polycystic kidney disease that comprises co-administering therapeutically effective amounts of xanthine oxide inhibitor and tolvaptan and/or lixivaptan.
A method of treating cystic disease in a subject in need, the method comprising co-administering a therapeutically effective amount of a uric acid lowering agent and gliflozin, wherein gliflozin is co-administered in an amount to increase the aqueous solubility and bioavailability of the uric acid lowering agent.
A method of treating a cystic disease, the method comprising co-administering a therapeutically effective amount of a xanthine oxidase inhibitor and a Sirtuin-1 activator.
A method of treating cystic disease in a subject in need, the method comprising co-administering a therapeutically effective amount of at least one xanthine oxidase inhibitor and an agent that directly or indirectly decreases expression of xanthine oxidase.
A composition comprising a therapeutically effective amount of a xanthine oxidase inhibitor and an agent that directly or indirectly decreases expression of xanthine oxidase.
Dependencies are inferred from the claim text.