Method and compositions for the treatment and detection of endothelin-1 related kidney diseases

Abstract

The present application relates to methods of treating HIV-associated nephropathy (HIVAN) and/or focal segmental glomerulosclerosis (FSGS) using endothelin-1 (ET-1) antagonists. The application further relates to a composition for the treatment of HIVAN and/or FSGS. A kit for detecting the presence of ET-1 or ET-1-associated biomarker in a biological sample is also disclosed.

1 - 17 . (canceled) 
     
     
         18 . A composition for the treatment of HIVAN or FSGS, said composition comprising an ET-1 antagonist, an angiotensin-converting enzyme (ACE) inhibitor and a pharmaceutically acceptable carrier. 
     
     
         19 . The composition of  claim 18 , wherein the ET-1 antagonist is a small molecule that binds to ET-1. 
     
     
         20 . The composition of  claim 18 , wherein the ET-1 antagonist is a small molecule that binds to ET-1 A . 
     
     
         21 . The composition of  claim 18 , wherein the ET-1 antagonist is selected from the group consisting of sitaxentan, ambrisentan, atrasentan, BQ-123, bosentan and tezosentan. 
     
     
         22 . The composition of  claim 18 , wherein the composition is formulated for a route of administration selected from the group consisting of intravenous, intramuscular, nasal, transdermal, transmucosal, buccal, sublingual, oral, subdermal, or combination thereof. 
     
     
         23 . A kit for detecting the presence of an ET-1-associated biomarker in a biological sample, wherein the kit comprises one or more reagents suitable for measuring the ET-1-associated biomarker in the biological sample. 
     
     
         24 . The kit of  claim 23 , wherein the reagents comprise an antibody, nucleic acid, or fragment thereof, wherein the antibody, nucleic acid, or fragment thereof specifically binds to the ET-1-associated biomarker. 
     
     
         25 . The kit of  claim 24 , further comprising instructions for using the kit to detect the ET-1-associated biomarker. 
     
     
         26 . The kit of  claim 23 , wherein the biological sample is blood, plasma, urine, saliva or tissue. 
     
     
         27 . The kit of  claim 23 , wherein said ET-1-associated biomarker is ET-1. 
     
     
         28 . The kit of  claim 27 , wherein the biological sample is blood. 
     
     
         29 . The kit of  claim 28 , comprising one or more reagents suitable for measuring ppET-1 mRNA, one or more reagents suitable for isolating macrophages in said blood sample, and HIV Nef protein. 
     
     
         30 . The kit of  claim 18 , wherein said ACE inhibitor is selected from the group consisting of sulfhydryl-containing agents; dicarboxylate-containing agents; and phosphonate-containing agents. 
     
     
         31 . The kit of  claim 30 , wherein said ACE inhibitor is captopril or zofenopril. 
     
     
         32 . The kit of  claim 30 , wherein said ACE inhibitor is selected from the group consisting of enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril and zofenopril. 
     
     
         33 . The kit of  claim 30 , wherein said ACE inhibitor is fosinopril.