Treatment of peritoneal injury using jak inhibitors

Abstract

The invention provides, in certain embodiments, a method of preventing and/or treating peritoneal injury and/or diminished function by administering an effective amount of one or more inhibitors of JAK. The invention also provides a pharmaceutical composition including a JAK inhibitor for the treatment of peritoneal injury and/or diminished function. In another aspect, the invention provides a method of detecting an indicator of peritoneal injury. The method entails assaying a biological sample for periostin, wherein the presence of periostin at an elevated level indicates the presence and/or degree of peritoneal injury. Also provided, are methods of identifying subject for treatment of peritoneal injury and/or diminished function, methods of determining progression of these conditions, as well as methods of determining subjects' response to treatment.

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         9 . A method of detecting an indicator of peritoneal injury, the method comprising assaying a biological sample for periostin protein or mRNA, wherein the biological sample is selected from the group consisting of a cell collected from used peritoneal dialysate, peritoneal tissue, and one or more fractions thereof, peritoneal fluid or one or more fractions thereof, and wherein the presence of periostin protein or mRNA at an elevated level indicates the presence and/or degree of peritoneal injury. 
     
     
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         11 . The method of  claim 9 , wherein periostin is detected as an indicator selected from the group consisting of a diagnostic indicator of peritoneal injury; an indicator of progression, remission, or relapse of peritoneal injury; and an indicator of response to treatment for peritoneal injury. 
     
     
         12 . The method of  claim 11 , wherein periostin is detected as an indicator of mesothelial to mesenchymal transition (MMT). 
     
     
         13 . A method for identifying a subject as a candidate for prevention and/or treatment of peritoneal injury, the method comprising:
 assaying a biological sample for periostin protein or mRNA, wherein the biological sample is selected from the group consisting of a cell collected from used peritoneal dialysate, peritoneal tissue, and one or more fractions thereof, peritoneal fluid or one or more fractions thereof; and   identifying the subject as a candidate for the prevention and/or treatment of peritoneal injury if periostin protein or mRNA is present in the biological sample at an elevated level.   
     
     
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         15 . The method of  claim 9 , wherein the biological sample comprises a human biological sample. 
     
     
         16 . The method of  claim 9 , wherein the biological sample comprises used peritoneal dialysate or a fraction thereof. 
     
     
         17 . The method of  claim 9 , wherein the biological sample comprises peritoneal fluid or a fraction thereof. 
     
     
         18 . The method of  claim 9 , wherein the biological sample comprises peritoneal tissue or a fraction thereof 
     
     
         19 . The method of  claim 9 any of  claims 9   18 , wherein the human is a human peritoneal dialysis patient. 
     
     
         20 . The method of  claim 15 , wherein the human is a human patient known to have, or suspected of having, peritoneal injury. 
     
     
         21 . A method for detecting an indicator of a subject's response to treatment for peritoneal injury, the method comprising assaying a biological sample obtained from a subject, after initiation of treatment for peritoneal injury, for periostin protein or mRNA, wherein the level of periostin protein or mRNA is positively correlated with the degree of peritoneal injury. 
     
     
         22 . The method of  claim 21 , wherein a baseline level of periostin protein or mRNA is measured prior to initiation of treatment for peritoneal injury and wherein the periostin protein or mRNA level of the biological sample after initiation of treatment is compared to the baseline level of periostin protein or mRNA. 
     
     
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         24 . The method of  claim 23 , wherein a decrease in the periostin protein or mRNA level of the biological sample after initiation of treatment, as compared to the baseline level of periostin protein or mRNA, indicates that the subject is responding to the treatment. 
     
     
         25 . The method of  claim 13 , wherein the subject is a peritoneal dialysis patient, and said treatment for peritoneal injury is selected from altering composition of the dialysate, terminating peritoneal dialysis, administering an effective amount of an inhibitor of the JAK/STAT protein dimer pathway, or a combination thereof. 
     
     
         26 . The method of  claim 21 , wherein said treatment for peritoneal injury comprises the method of administering an effective amount of an inhibitor of the JAK/STAT protein dimer pathway to a subject who is at risk of peritoneal injury and/or has at least one symptom or sign of peritoneal injury and/or of diminished peritoneal membrane function, wherein the effective amount is an amount sufficient to reduce the subject's risk of peritoneal injury and/or mitigate the subject's at least one symptom or sign of peritoneal injury and/or improve peritoneal membrane function. 
     
     
         27 . (canceled) . 
     
     
         28 . The method of  claim 9 , the method additionally comprising detecting one or more additional indicators of peritoneal injury selected from the group consisting of PDGF, collagen IV, the peritoneal equilibration test (PET), and encapsulating peritoneal sclerosis (EPS). 
     
     
         29 . The method of  claim 9 , wherein periostin protein or mRNA is detected by a method selected from the group consisting of an immunoassay, electrochemiluminescence, HPLC, mass spectroscopy, hybridization, and polymerase chain reaction (PCR). 
     
     
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         31 . The method of  claim 9 , wherein periostin protein or mRNA is detected in an assay wherein the periostin protein or mRNA, or DNA derived therefrom, is transformed from a free state to a bound state by forming a complex with another assay component, wherein the another assay component comprises a capture agent, and the complex comprises an analyte/capture agent complex. 
     
     
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         33 . The method of  claim 31 , wherein the capture agent comprises one or more monoclonal antibodies, or fragments thereof, or polyclonal antibodies. 
     
     
         34 . The method of  claim 31 , wherein the capture agent comprises one or more nucleic acid probes. 
     
     
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