Methods for predicting the progression and treating a chronic kidney disease in a patient

Abstract

The present invention relates to a method for predicting the progression of chronic kidney disease (CKD) in a patient and also to an inhibitor of NGAL gene expression or an NGAL antagonist for use in the prevention or the treatment of CKD.

1 . A method for predicting the progression of chronic kidney disease (CKD) or for monitoring CKD therapy in a patient, comprising the following steps:
 a. providing a biological sample from said patient suffering from CKD,   b. determining the expression level of Neutrophil Gelatinase-Associated Lipocalin (NGAL) gene, and   c. correlating the expression level of NGAL gene with the prediction of the progression of CKD.   
     
     
         2 . The method according to  claim 1 , wherein said expression level of NGAL gene is compared to a predetermined value. 
     
     
         3 . The method according to  claim 1 , wherein said expression level of NGAL gene is determined by determining the quantity of NGAL mRNA and said biological sample is a cell or tissue sample. 
     
     
         4 . The method according to  claim 3 , wherein said tissue sample is a kidney biopsy. 
     
     
         5 . The method according to  claim 1 , wherein said expression level of NGAL gene is determined by measuring the concentration of NGAL protein in a biological sample obtained from said patient. 
     
     
         6 . The method according to  claim 5 , wherein said biological sample is a blood sample, a serum sample, a plasma sample or a urine sample. 
     
     
         7 . The method according to  claim 5 , wherein the concentration of NGAL protein is measured by immunoassay. 
     
     
         8 . The method according to  claim 1 , wherein the CKD is selected in the group consisting of polycystic kidney disease glomerulonephritis, interstitial nephritis, nephropathy and obstructive uropathy. 
     
     
         9 - 13 . (canceled) 
     
     
         14 . The method of  claim 8 , wherein said polycystic kidney disease is Autosomal Dominant Polycystic Kidney Disease (ADPKD) or Autosomal Recessive Polycystic Kidney Disease (ARPKD). 
     
     
         15 . A method of preventing or treating chronic kidney disease (CKD) in a patient in need thereof, comprising
 administering to said patient an inhibitor of Neutrophil Gelatinase-Associated Lipocalin (NGAL) gene expression.   
     
     
         16 . The method of  claim 15 , wherein said inhibitor is selected from the group consisting of antisense RNA or DNA molecules, small inhibitory RNAs (siRNAs), short hairpin RNA and ribozymes. 
     
     
         17 . A method of preventing or treating chronic kidney disease (CKD) in a patient in need thereof, comprising
 administering to said patient an antagonist of Neutrophil Gelatinase-Associated Lipocalin (NGAL) gene expression.   
     
     
         18 . The method of  claim 17 , wherein said antagonist is an antibody or an aptamer directed against NGAL. 
     
     
         19 . A pharmaceutical composition comprising
 an inhibitor of Neutrophil Gelatinase-Associated Lipocalin (NGAL) gene expression selected from the group consisting of antisense RNA or DNA molecules, small inhibitory RNAs (siRNAs), short hairpin RNA and ribozymes; or   an NGAL antagonist selected from an antibody and an aptamer directed against NGAL; and   a pharmaceutically acceptable vehicle.   
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein said pharmaceutical composition is formulated: for parenteral administration, as a solid tablet, as a liposomal formulation, or as a time release capsule. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein said parenteral administration is via intravenous or intramuscular injection.