Linaclotide reduced the TMAO level ameliorating cardiac fibrosis in an adenine-induced CKD model

The coexistence of chronic kidney disease (CKD) and cardiac vascular disease (CVD) leads to a dramatic increase in the risk of mortality as well as in the difficulty of clinical management. Recently, it is well known that trimethylamine-N-oxide (TMAO) which is generated from dietary phosphatidylcholine or carnitine derived by gut microbiota, and the increased TMAO level was a strong risk of major adverse cardiovascular events. In addition, the increase of TMAO in CKD also directly contributes to progressive renal fibrosis and poorer long-term survival in CKD patients. Because guanylate cyclase C agonist (GCCA) linaclotide is a GC-C agonist approved by the FDA for treatment of constipation of irritable bowel syndrome and also constipation is one of the predicting factor of CKD and ESRD, linaclotide may be an candidate tool for intervening and preventing the progression of cardio-renal syndrome in a CKD patients. We therefore investigated the effect of linaclotide using an adenine-induced renal failure (RF) mouse model.