Acth prophylactic treatment of renal disorders

Abstract

Provided herein are methods for prophylactic treatment of renal disorders comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual suspected of having, predisposed to, or at risk of developing a renal disorder.

1 .- 19 . (canceled) 
     
     
         20 . A method of prophylactically treating chronic kidney injury or end-stage renal disease in an individual in need thereof, comprising selecting an individual suspected of having, predisposed to, or at risk of developing chronic kidney injury, and administering a composition comprising an adrenocorticotropic hormone (ACTH) peptide to the individual in need thereof, wherein the ACTH peptide is administered as a first dose and one or more subsequent doses, and wherein the ACTH peptide is an ACTH peptide preparation comprising at least one ACTH peptide having about 90% or greater homology with a full-length porcine ACTH sequence. 
     
     
         21 . The method of  claim 20 , wherein the ACTH peptides in the preparation are derived from porcine pituitary glands. 
     
     
         22 . The method of  claim 20 , wherein the ACTH peptide preparation is formulated in a gel. 
     
     
         23 . The method of  claim 20 , wherein selection of the individual is based upon prolonged or gradual decrease of renal tubular cell function or glomerular filtration rate (GFR) during which the rate of change of the function or rate can vary. 
     
     
         24 . The method of  claim 20 , wherein selection of the individual is based upon a prolonged or gradual worsening of renal tubular cell injury during which the rate of change of the injury can vary. 
     
     
         25 . The method of  claim 20 , wherein the first dose of the ACTH peptide preparation comprises a dose between about 10 IU and about 150 IU, and the one or more subsequent doses of the ACTH peptide preparation is administered about every day, about every 2 days, about every 5 days, about every week, about every two weeks, about every three weeks, about every month, about every two months, or any combination thereof. 
     
     
         26 . The method of  claim 20 , wherein the first dose of the ACTH peptide preparation comprises a dose between about 10 IU and about 150 IU, and the one or more subsequent doses of the ACTH peptide preparation are between about 20%-80% of the first dose. 
     
     
         27 . The method of  claim 20 , wherein the first dose and the one or more subsequent doses of the ACTH peptide preparation comprises a first dose of between about 10 IU and about 150 IU, and the one or more subsequent doses of the ACTH peptide preparation are between about 10 IU and about 80 IU, the first dose and the one or more subsequent doses of the ACTH peptide preparation are intermittent. 
     
     
         28 . The method of  claim 20 , further comprising administering to the individual a second therapeutic agent. 
     
     
         29 . The method of  claim 28 , wherein the second therapeutic agent is selected from the group consisting of an angiotensin-converting enzyme inhibitor, an angiotensin receptor blocker, a phosphate binder, a hepatocyte growth factor (HGF), a corticosteroid, erythropoietin, calcitriol, bardoxolone methyl, medoxomil, sulodexide and avosentan. 
     
     
         30 . A method of prophylactically treating chronic kidney injury or end-stage renal disease in an individual in need thereof, comprising selecting an individual suspected of having, predisposed to, or at risk of developing chronic kidney injury, and administering a composition comprising an adrenocorticotropic hormone (ACTH) peptide to the individual in need thereof, wherein the ACTH peptide is administered as a first dose and one or more subsequent doses; and wherein the ACTH peptide is an ACTH peptide preparation comprising at least one ACTH peptide having about 90% or greater homology with;
 (a) an ACTH 1-39  peptide comprising the sequence:   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   H -Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly- 
                 
                     
                       1   2   3   4   5   6   7   8   9   10 
                 
                     
                     
                 
                     
                   Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val- 
                 
                     
                   11  12  13  14  15  16  17  18  19  20 
                 
                     
                     
                 
                     
                   Lys-Val-Tyr-Pro-Asp-Gly-Ala-Glu-Asp-Gln- 
                 
                     
                   21  22  23  24  25  26  27  28  29  30 
                 
                     
                     
                 
                     
                   Leu-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH 
                 
                     
                   31  32  33  34  35  36  37  38  39; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (b) an ACTH 1-24  peptide comprising the sequence: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 2) 
                 
                     
                   H -Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly- 
                 
                     
                       1   2   3   4   5   6   7   8   9   10 
                 
                     
                     
                 
                     
                   Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val- 
                 
                     
                   11  12  13  14  15  16  17  18  19  20 
                 
                     
                     
                 
                     
                   Lys-Val-Tyr-Pro 
                 
                     
                   21  22  23  24; 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       or
 (c) an ACTH 1-17  peptide comprising the sequence: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 3) 
                 
                     
                   H -Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly- 
                 
                     
                       1   2   3   4   5   6   7   8   9   10 
                 
                     
                     
                 
                     
                   Lys-Pro-Val-Gly-Lys-Lys-Arg 
                 
                     
                   11   12  13  14   15  16  17. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         31 . The method of  claim 30 , wherein the ACTH peptide is ACTH 1-39  peptide consisting of the sequence: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   H -Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly- 
                 
                     
                       1   2   3   4   5   6   7   8   9   10 
                 
                     
                     
                 
                     
                   Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val- 
                 
                     
                   11  12  13  14  15  16  17  18  19  20 
                 
                     
                     
                 
                     
                   Lys-Val-Tyr-Pro-Asp-Gly-Ala-Glu-Asp-Gln- 
                 
                     
                   21  22  23  24  25  26  27  28  29  30 
                 
                     
                     
                 
                     
                   Leu-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH 
                 
                     
                   31  32  33  34  35  36  37  38  39. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         32 . The method of  claim 30 , wherein the ACTH peptide is ACTH 1-24  peptide consisting of the sequence: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 2) 
                 
                     
                   H -Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly- 
                 
                     
                       1   2   3   4   5   6   7   8   9   10 
                 
                     
                     
                 
                     
                   Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val- 
                 
                     
                   11  12  13  14  15  16  17  18  19  20 
                 
                     
                     
                 
                     
                   Lys-Val-Tyr-Pro 
                 
                     
                   21  22  23  24. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         33 . The method of  claim 30 , wherein the ACTH peptide is ACTH 1-17  peptide consisting of the sequence: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 3) 
                 
                     
                   H -Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly- 
                 
                     
                       1   2   3   4   5   6   7   8   9   10 
                 
                     
                     
                 
                     
                   Lys-Pro-Val-Gly-Lys-Lys-Arg 
                 
                     
                   11  12  13  14  15  16  17. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         34 . The method of  claim 30 , wherein the ACTH peptides in the preparation are derived from porcine pituitary glands. 
     
     
         35 . The method of  claim 30 , wherein the ACTH peptide preparation is formulated in a gel. 
     
     
         36 . The method of  claim 30 , wherein selection of the individual is based upon prolonged or gradual decrease of renal tubular cell function or glomerular filtration rate (GFR) during which the rate of change of the function or rate can vary. 
     
     
         37 . The method of  claim 30 , wherein selection of the individual is based upon a prolonged or gradual worsening of renal tubular cell injury during which the rate of change of the injury can vary. 
     
     
         38 . The method of  claim 30 , wherein the first dose of the ACTH peptide preparation comprises a dose between about 10 IU and about 150 IU, and the one or more subsequent doses of the ACTH peptide preparation is administered about every day, about every 2 days, about every 5 days, about every week, about every two weeks, about every three weeks, about every month, about every two months, or any combination thereof. 
     
     
         39 . The method of  claim 30 , further comprising administering to the individual a second therapeutic agent. 
     
     
         40 . The method of  claim 39 , wherein the second therapeutic agent is selected from the group consisting of an angiotensin-converting enzyme inhibitor, an angiotensin receptor blocker, a phosphate binder, a hepatocyte growth factor (HGF), a corticosteroid, erythropoietin, calcitriol, bardoxolone methyl, medoxomil, sulodexide and avosentan.