Urine and serum biomarkers associated with diabetic nephropathy

Abstract

Use of urine and serum biomarkers in diagnosing diabetic nephropathy, staging diabetic nephropathy, monitoring diabetic nephropathy progress, and assessing efficacy of diabetic nephropathy treatments. These biomarkers include urine precursor alpha-2-HS-glycoprotein, urine alpha-1 antitrypsin, urine alpha-1 acid glycoprotein, urine osteopontin, serum osteopontin, their fragments, and combinations thereof.

1 . An isolated antibody specifically binding to a peptide selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 2) 
                 
                     
                   MGVVSLGSPSGEVSHPRKT, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   KGKWERPFEVKDTEEEDF, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   MIEQNTKSPLFMGKVVNPTQK, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFA, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   GQEHFAHLLILRDTKTYMLADVNDEKNWGLS, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   YPDAVATWLNPDPSQKQ NLLAPQNAVSSEETNDFKQETLPSK, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   KYPDAVATWLNPDPSQKQNLLAPQTLPSK. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . The antibody of  claim 1 , specifically binding to MGVVSLGSPSGEVSHPRKT (SEQ ID NO:2). 
     
     
         3 . The antibody of  claim 1 , specifically binding to KGKWERPFEVKDTEEEDF (SEQ ID NO:3). 
     
     
         4 . The antibody of  claim 1 , specifically binding to MIEQNTKSPLFMGKVVNPTQK (SEQ ID NO:4). 
     
     
         5 . The antibody of  claim 1 , specifically binding to EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFA (SEQ ID NO:6). 
     
     
         6 . The antibody of  claim 1 , specifically binding to GQEHFAHLLILRDTKTYMLADVNDEKNWGLS (SEQ ID NO:7). 
     
     
         7 . The antibody of  claim 1 , specifically binding to YPDAVATWLNPDPSQKQ NLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8). 
     
     
         8 . The antibody of  claim 1 , specifically binding to KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9). 
     
     
         9 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         10 . The antibody of  claim 1 , wherein the antibody is a whole immunoglobulin molecule. 
     
     
         11 . A kit for diagnosing diabetic nephropathy, comprising two, three, or four antibodies, each of which is capable of binding to (i) alpha-2-HS-glycoprotein, (ii) alpha-1 antitrypsin, (iii) alpha-1 acid glycoprotein, or (iv) osteopontin, wherein the two, three, or four antibodies have different antigen specificities. 
     
     
         12 . The kit of  claim 11 , wherein the antibodies are whole immunoglobulin molecules. 
     
     
         13 . The kit of  claim 11 , wherein the antibodies are monoclonal antibodies. 
     
     
         14 . The kit of  claim 11 , wherein the antibodies are selected from the group consisting of:
 an antibody specifically binding to MGVVSLGSPSGEVSHPRKT (SEQ ID NO:2);   an antibody specifically binding to KGKWERPFEVKDTEEEDF (SEQ ID NO:3);   an antibody specifically binding to MIEQNTKSPLFMGKVVNPTQK (SEQ ID NO:4);   an antibody specifically binding to EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFA (SEQ ID NO:6);   an antibody specifically binding to GQEHFAHLLILRDTKTYMLADVNDEKNWGLS (SEQ ID NO:7);   an antibody specifically binding to YPDAVATWLNPDPSQKQ NLLAPQNAVSSEETNDFKQETLPSK (SEQ ID NO:8); and   an antibody specifically binding to KYPDAVATWLNPDPSQKQNLLAPQTLPSK (SEQ ID NO:9).   
     
     
         15 . The kit of  claim 11 , consisting essentially of two, three, or four antibodies, each of which is capable of binding to (i) alpha-2-HS-glycoprotein, (ii) alpha-1 antitrypsin, (iii) alpha-1 acid glycoprotein, or (iv) osteopontin, wherein the two, three, or four antibodies have different antigen specificities. 
     
     
         16 . The kit of  claim 11 , further comprising reagents and materials for an immunoassay, the immunoassay being ELISA, Westernblot, RIA, FIA or LIA.