Treating and preventing disease with tma and tmao lowering agents

Abstract

Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.

What is claimed is: 
     
         1 . A method of treating or preventing kidney and/or cardiovascular disease comprising:
 treating a subject with a TMA and/or TMAO sequestering agent, wherein:
 i) said subject has symptoms of kidney and/or cardiovascular disease and said treating reduces or eliminates at least one symptom of said kidney and/or cardiovascular disease; 
 ii) said subject is apparently healthy, but has elevated levels of TMAO, and said treating prevents the development of chronic kidney and/or cardiovascular disease in said subject; or 
 iii) said subject has age-related decline in kidney function, and said treating prevents or attenuates further decline in said kidney function. 
   
     
     
         2 . The method of  claim 1 , wherein a sample from said subject is assayed to determine levels of eGFR, eCrCl, Cystatin C, KIM1, microalbuniuria (an elevated urine albumin/Creatinine ratio), trimethylamine N-oxide (TMAO), TMA, and/or a TMA-containing compound prior to and/or after said treating. 
     
     
         3 . The method of  claim 2 , wherein said sample is selected from whole blood, serum, plasma, urine, and saliva. 
     
     
         4 . The method of  claim 1 , wherein said TMA and/or TMAO sequestering agent comprises activated charcoal. 
     
     
         5 . The method of  claim 1 , wherein said TMA and/or TMAO sequestering agent comprises copper chlorophyllin. 
     
     
         6 . The method of  claim 1 , wherein said TMA and/or TMAO sequestering agent comprises a TMA sequestering agent. 
     
     
         7 . The method of  claim 1 , wherein said TMA and/or TMAO sequestering agent comprises a TMAO sequestering agent. 
     
     
         8 . The method of  claim 1 , wherein said subject is a human. 
     
     
         9 . The method of  claim 1 , wherein said subject has symptoms of kidney disease. 
     
     
         10 . The method of  claim 1 , wherein said subject has symptoms of cardiovascular disease. 
     
     
         11 . The method of  claim 1 , wherein said subject is apparently healthy and has elevated levels of TMAO. 
     
     
         12 . The method of  claim 1 , wherein said subject has age-related decline in kidney function. 
     
     
         13 . A system comprising:
 a) a report for a patient with kidney and/or cardiovascular disease indicating that said patient has elevated levels of TMA and/or TMAO; and   b) a TMA and/or TMAO sequestering agent.   
     
     
         14 . The system of  claim 13 , wherein said TMA and/or TMAO sequestering agent comprises a TMA sequestering agent. 
     
     
         15 . The system of  claim 13 , wherein said TMA and/or TMAO sequestering agent comprises a TMAO sequestering agent. 
     
     
         16 . The system of  claim 13 , wherein said report is for a patient with kidney disease. 
     
     
         17 . The system of  claim 13 , wherein said report is for a patient with cardiovascular disease. 
     
     
         18 . The system of  claim 13 , wherein said TMA and/or TMAO sequestering agent comprises copper chlorophyllin. 
     
     
         19 . The system of  claim 13 , wherein said TMA and/or TMAO sequestering agent comprises activated charcoal. 
     
     
         20 . The system of  claim 13 , wherein said patient is a human.