Method for the Early Detection of Renal Disease Using Proteomics

Abstract

A method for the detection of an early biomarker for assessing a change in renal status in a mammalian subject following a renal event. The method typically includes the steps of (a) providing a body fluid sample obtained from a mammalian subject; (b) analyzing the molecular weight of the proteins in the sample using proteome analysis; and (c) identifying the presence of a protein in the sample selected from the group consisting of a 6.4 kDa protein, a 28.5 kDa protein, a 33 kDa protein, a 44 kDa protein, a 67 kDa protein, and combinations thereof. The presence of one of these proteins can serve as an early biomarker for assessing a change in renal status. The levels of these proteins can be compared to predetermined levels, and thus provide a determination of the subject's renal status. The invention also includes a method of assessing the administration of aprotinin during cardio-pulmonary bypass surgery and provides for methods where the level of the 6.4 kDa biomarker in the subject's urine directs a caregiver's therapeutic decision regarding the intra-operative administration of aprotinin.

1 . A method for the detection of an early biomarker for assessing a change in renal status in a mammalian subject following a renal event, the method comprising the steps of: 
 a. providing a body fluid sample obtained from a mammalian subject following a renal event;    b. analyzing the molecular weight of the proteins in the sample using proteome analysis; and    c. identifying the presence of a protein in the sample selected from the group consisting of a 6.4 kDa protein, a 28.5 kDa protein, a 33 kDa protein, a 44 kDa protein, a 67 kDa protein and combinations thereof, the presence of the protein serving as an early biomarker for assessing a change in renal status.    
   
   
       2 . The method of  claim 1 , wherein the body fluid for the sample is selected from the group consisting of urine, blood, serum, plasma, saliva, lymph, cerebrospinal fluid, cystic fluid, ascites, stool, bile, and any other isolatable body fluid.  
   
   
       3 . The method of  claim 1 , wherein the body fluid for the sample is isolated urine.  
   
   
       4 . The method of  claim 1 , wherein proteome analysis is accomplished by the SELDI-TOF-MS technique.  
   
   
       5 . The method of  claim 1 , wherein the protein is a 6.4 kDa protein.  
   
   
       6 . The method of  claim 1 , wherein the protein is a plurality of proteins comprising a 28.5 kDa protein, a 33 kDa protein, a 44 kDa protein, and a 67 kDa protein.  
   
   
       7 . The method of  claim 1 , wherein the protein is a 28.5 kDa protein.  
   
   
       8 . The method of  claim 1 , wherein the protein is a 44 kDa protein.  
   
   
       9 . The method of  claim 1 , wherein the protein is selected from the group consisting of a 33 kDa protein, a 67 kDa protein and combinations thereof.  
   
   
       10 . A method for determining the renal status of a mammalian subject within 48 hours following a renal event, the method comprising the steps of: 
 a. providing a body fluid sample obtained from a mammalian subject at a time within 48 hours following a renal event;    b. separating the proteins in the body fluid sample by molecular weight using proteome analysis;    c. identifying a separated protein based on the molecular weight of the separated protein, the separated protein being selected from the group consisting of a 6.4 kDa protein, a 28.5 kDa protein, a 33 kDa protein, a 44 kDa protein, a 67 kDa protein, and combinations thereof; and    d. comparing the level of each identified protein to a predetermined level thereof, the comparison providing a determination of the subject's renal status.    
   
   
       11 . The method of  claim 10 , wherein the separated protein is a plurality of proteins comprising a 28.5 kDa protein, a 33 kDa protein, a 44 kDa protein, and a 67 kDa protein.  
   
   
       12 . The method of  claim 10 , wherein the separated protein is a 6.4 kDa protein.  
   
   
       13 . The method of  claim 10 , wherein the body fluid for the sample is selected from the group consisting of urine, blood, serum, plasma, saliva, lymph, cerebrospinal fluid, cystic fluid, ascites, stool, bile, and any other isolatable body fluid.  
   
   
       14 . The method of  claim 10 , wherein the body fluid for the sample is isolated urine.  
   
   
       15 . The method of  claim 10 , wherein proteome analysis is accomplished by the SELDI-TOF-MS technique.  
   
   
       16 . A method for assessing the administration of aprotinin during cardiopulmonary bypass surgery, the method comprising: 
 a. providing a urine sample obtained from a subject receiving cardio-pulmonary bypass surgery;    b. separating the proteins in the sample by molecular weight using proteome analysis;    c. identifying the presence of a 6.4 kDa protein; and    d. comparing the level of the 6.4 kDa protein to a predetermined level thereof,    wherein the comparison directs a caregiver's therapeutic decision regarding the intra-operative administration of aprotinin during cardio-pulmonary bypass surgery.    
   
   
       17 . The method of  claim 16 , wherein the comparison step reveals that the subject is depositing an increased amount of the 6.4 kDa protein in the urine, leading to the determination that the intra-operative administration of aprotinin should be decreased.  
   
   
       18 . The method of  claim 16 , wherein the comparison step reveals that the subject is depositing a high amount of the 6.4 kDa protein in the urine, leading to the determination that the intra-operative administration of aprotinin should be stopped.  
   
   
       19 . The method of  claim 16 , wherein the comparison step reveals that the subject is not depositing the 6.4 kDa protein in the urine, leading to the determination that the intra-operative administration of aprotinin can be continued.  
   
   
       20 . The method of  claim 16 , wherein proteome analysis is accomplished by the SELDI-TOF-MS technique.