Protein-bound uremic toxins: a long overlooked culprit in cardiorenal syndrome

Protein-bound uremic toxins (PBUTs) accumulate once renal excretory function declines and are not cleared by dialysis. There is increasing evidence that PBUTs exert toxic effects on many vital organs, including the kidney, blood vessels, and heart. It has been suggested that PBUTs are likely to be a potential missing link in cardiorenal syndrome, based on the high incidence of cardiovascular events and mortality in the dialysis population, which are dramatically reduced in successful kidney transplant recipients. These data have led the call for more effective dialysis or additional adjunctive therapy to eradicate these toxins and their adverse biological effects. Indoxyl sulfate and p-cresyl sulfate are the two most problematic PBUTs, conferring renal and cardiovascular toxicity, and are derived from dietary amino acid metabolites by colonic microbial organisms. Therefore, targeting the colon where these toxins are initially produced appears to be a potential therapeutic alternative for patients with chronic kidney disease. This strategy, if approved, is likely to be applicable to predialysis patients, thereby potentially preventing progression of chronic kidney disease to end-stage renal disease as well as preventing the development of cardiorenal syndrome.