New insights into uremic toxicity

Purpose of review: Our concept of uremia has expanded to encompass the illness patients begin to suffer as glomerular filtration rate declines long before the onset of end-stage renal disease (ESRD) not explained by known derangements in volume status or metabolic parameters. New insights into the accumulation of uremic toxins and the loss of function of hormones and enzymes provide important information on the etiology of uremia. Recent findings New data are accumulating on the identity and toxicity of uremic toxins and the syndromes that encompass uremia. p-Cresol sulfate and indoxyl sulfate are small, protein-bound molecules that are poorly cleared with dialysis. These molecules have been linked to cardiovascular disease and oxidative injury. Impaired immunity plays a central role in the morbidity of ESRD and may be both the result of uremic toxicity and a contributor to oxidative stress in ESRD. Uremic cachexia is an underrecognized uremic syndrome. New insights into disordered feeding circuits in ESRD may lead to novel therapies using hormone agonists. Summary Mortality in ESRD remains unacceptably high. It is hoped that as knowledge emerges on the causes and consequences of uremia, we are embarking on an era not only of new insights but also new and effective treatments for patients with the ill effects of uremia.