A nexus of progression of chronic kidney disease: charcoal, tryptophan and profibrotic cytokines.
Fibrosis plays a role in the pathogenesis of progressive chronic kidney disease (CKD). The inhibition of the renin-angiotensin system, which promotes fibrosis, has become the standard of care in the treatment of patients with CKD. A novel charcoal compound, AST-120, has been used for over a decade in Japan to prevent progression of CKD. It is thought that the oral administration of AST-120 blocks the intestinal absorption of tryptophan-derived indole. This prevents the hepatic conversion of indole to indoxyl sulfate (IS). IS has been shown to stimulate the production of profibrotic cytokines such as transforming growth factor-beta. AST-120 lowers IS in a dose dependent fashion and does not change the creatinine appearance rate in the urine. Enteric capsules containing Bifidobacterium longum have been shown to prevent progression of CKD in a preliminary study. These findings suggest that prospective clinical trials be undertaken to determine if these other potential methods of inhibiting fibrosis are useful in slowing progressive CKD.
Schulman
Gerald
G
Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. gerald.schulman@vanderbilt.edu
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002244:Carbon / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D023381:Endpoint Determination; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007200:Indican / Q000097:blood; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage*; D014364:Tryptophan / Q000378:metabolism
D016207:Cytokines; D010087:Oxides; D002244:Carbon; D014364:Tryptophan; C040896:AST 120; D007200:Indican