Levels of over 70 chemicals are elevated in uremic plasma, leading to the hypothesis that these toxins, individually or in combination, cause uremic organ dysfunction and produce the symptoms. For over 100 years it has been observed that limiting protein intake markedly improves the symptoms of uremia. Urea, the major breakdown product of proteins, reproduces a few of the neurobehavioral uremic symptoms, but only at very high concentrations. Other potential uremic toxins include cyanate, guanidines, polyamines, and b2-microglobulin. Ammonia is not a toxin candidate, since ammonia levels are not elevated in ESRD patients.
In conclusion, while toxins from ESRD excretory failure are definitely a factor in uremia, they cannot explain all its clinical features. In addition, if uremia was simply a toxidrome, then dialysis should reverse all its untoward effects. Yet, many uremic organ dysfunctions persist after dialysis, and other processes are clearly important.
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