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High urea levels in chronic kidney failure might be toxic after all

Date:
December 2, 2009
Source:
Journal of Clinical Investigation
Summary:
It is thought that the elevated levels of urea (the byproduct of protein breakdown that is excreted in the urine) in patients with end-stage kidney failure are not particularly toxic. However, researchers have now generated evidence in mice that high levels of urea are indeed toxic. Blocking the effects of high levels of urea might therefore be of benefit to patients with end-stage kidney disease.
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It is thought that the elevated levels of urea (the byproduct of protein breakdown that is excreted in the urine) in patients with end-stage kidney failure are not particularly toxic. However, a team of researchers, at Albert Einstein College of Medicine, New York, and Università degli Studi di Foggia, Italy, has now generated evidence in mice that high levels of urea are indeed toxic. They therefore suggest that blocking the effects of high levels of urea might benefit patients with end-stage kidney disease.

The research is published in the Journal of Clinical Investigation.

The team, led by Michael Brownlee and Ida Giardino, found that fat cells cultured in the presence of disease-relevant levels of urea produced toxic molecules known as reactive oxygen species (ROS). These caused the fat cells to take on characteristics of fat cells in patients with end-stage kidney disease (such as an inability to respond to the hormone insulin, which is also a key feature of type 2 diabetes).

In a mouse model of end-stage kidney disease, increased ROS levels were detected, as was resistance to the effects of insulin.

As treatment with an antioxidant (which will act to mop up the ROS) restored the ability of mice to respond to insulin, the authors suggest that drugs targeting ROS might help improve the quality of life and lifespan of individuals with end-stage kidney disease.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Maria D%u2019Apolito1, Xueliang Du2, Haihong Zong2, Alessandra Catucci1, Luigi Maiuri1, Tiziana Trivisano3, Massimo Pettoello-Mantovani1, Angelo Campanozzi1, Valeria Raia4, Jeffrey E. Pessin2, Michael Brownlee2 and Ida Giardino. Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure. Journal of Clinical Investigation, Dec. 1, 2009 DOI: 10.1172/JCI37672

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Journal of Clinical Investigation. "High urea levels in chronic kidney failure might be toxic after all." ScienceDaily. ScienceDaily, 2 December 2009. <www.sciencedaily.com/releases/2009/12/091201182610.htm>.
Journal of Clinical Investigation. (2009, December 2). High urea levels in chronic kidney failure might be toxic after all. ScienceDaily. Retrieved May 24, 2015 from www.sciencedaily.com/releases/2009/12/091201182610.htm
Journal of Clinical Investigation. "High urea levels in chronic kidney failure might be toxic after all." ScienceDaily. www.sciencedaily.com/releases/2009/12/091201182610.htm (accessed May 24, 2015).

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