Uremic toxins: an integrated overview of classification and pathobiology

Abstract Uremic toxins are defined as substances, organic or inorganic, that accumulate in the body fluids of subjects with acute or chronic kidney disease and impaired kidney function. They collectively contribute to the diverse clinical manifestations of the uremic syndrome. They can be classified according to physicochemical properties, especially with regard to molecular size and protein binding, and organ tropism for their adverse effects. Many such substances have been identified. A substantial number of uremic toxins are the product of protein metabolism and are influenced by colonic microbiota and enterohepatic circulation. The composition of the diet, particularly the contributions of animal versus vegetable proteins, influences the generation of certain uremic toxins. Many low- and middle-molecular-weight toxins are generally removed from the body by glomerular filtration, while protein-bound uremic toxins utilize tubular secretion as a removal pathway. Some uremic toxins are elaborated endogenously by dysregulated secretion (e.g., parathyroid hormone). Dialysis is efficient for the removal of low-molecular-weight uremic toxins, but very inefficient for the removal of high-molecular-weight or protein-bound uremic toxins. This chapter provides an integrated overview of the present status of the biology and clinical significance of uremic toxins.