Uremic toxins, and their effect on intermediary metabolism

In the late stages of chronic renal damage the functional mass of the kidney is reduced and there is progression to renal insufficiency, usually called uremia, in which all aspects of renal function are affected. The complexity of the biochemical aspects of the syndrome of uremia is a manifestation of the wide variety and nature of the individual disorders that contribute to the pathogenesis of the final clinical syndrome. One major feature is the retention of metabolic end products and their effects, as toxins, on intermediary metabolism. The retained end products, working singly or in combination, probably affect metabolic pathways by some modification of enzymic reactions. They act at the cell membrane level. Although "middle molecules" have been incriminated as uremic toxins, recent attention has also focused on trace elements--especially aluminum, which has been implicated in the pathogenesis of two major disorders, osteomalacic dialysis osteodystrophy and dialysis encephalopathy.