Inhibition of PKC to treat permability failure

Abstract

The invention features a method of treating a subject, e.g., a subject having permeability disjunction, which includes administering to the subject peritoneal dialysis fluid which includes an inhibitor of PKC, e.g., an inhibitor of PKC β. The invention also features an improved peritoneal dialysis fluid and methods of making such dialysis fluid.

1 . A method of treating a subject, comprising: 
 introducing into said subject a peritoneal dialysis fluid which includes an inhibitor of a PKC, thereby treating said subject.    
     
     
         2 . The method of  claim 1 , wherein said inhibitor is a specific inhibitor of PKC.  
     
     
         3 . The method of  claim 2 , wherein said inhibitor is selected from the group consisting of: an inhibitor of a PKC β, an inhibitor of PKC γ, and an inhibitor of PKC δ.  
     
     
         4 . The method of  claim 2 , wherein said inhibitor is an inhibitor of PKC β.  
     
     
         5 . The method of  claim 4 , wherein said inhibitor is an inhibitor of PKC β1.  
     
     
         6 . The method of  claim 4 , wherein said inhibitor is a bis (indolyl) maleimide.  
     
     
         7 . The method of  claim 6 , wherein said inhibitor is LY333531.  
     
     
         8 . The method of  claim 7 , wherein said LY333531 is present in said dialysis fluid at about 1-1,000 nanometers.  
     
     
         9 . The method of  claim 1 , wherein said dialysis fluid has a concentration of glucose of about 200 nM.  
     
     
         10 . The method of  claim 1 , wherein said subject has previously received peritoneal dialysis.  
     
     
         11 . The method of  claim 1 , wherein said subject has been a peritoneal dialysis patient for at least 2 to 24 months.  
     
     
         12 . The method of  claim 1 , wherein said subject has already developed permeability disjunction.  
     
     
         13 . The method of  claim 1 , wherein said subject has not yet developed permeability disjunction.  
     
     
         14 . The method of  claim 1 , wherein said subject is at risk for renal failure.  
     
     
         15 . The method of  claim 14 , wherein said subject is in end-stage renal failure.  
     
     
         16 . A peritoneal dialysis fluid comprising an inhibitor of a PKC.  
     
     
         17 . The dialysis fluid of  claim 16 , wherein said inhibitor is a specific inhibitor of PKC.  
     
     
         18 . The dialysis fluid of  claim 17 , wherein said inhibitor is an inhibitor of PKC β.  
     
     
         19 . The dialysis fluid of  claim 18 , wherein said inhibitor is a bis (indolyl) maleimide.  
     
     
         20 . The dialysis fluid of  claim 19 , wherein said inhibitor is LY333531.  
     
     
         21 . The dialysis fluid of  claim 20 , wherein said LY333531 is present in said dialysis fluid at about 1-1,000 nanometers.  
     
     
         22 . The dialysis fluid of  claim 16 , wherein said dialysis fluid has a concentration of glucose of about 200 nM.  
     
     
         23 . A method of making an improved peritoneal dialysis fluid, comprising: 
 providing a peritoneal dialysis fluid; and    adding to that fluid an inhibitor of a PKC, to thereby provide an improved dialysis fluid.    
     
     
         24 . The method of  claim 23 , wherein said inhibitor is LY333531.