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Toxins 2017, 9(4), 114; doi:10.3390/toxins9040114

Inflammatory Cytokines as Uremic Toxins: “Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son”

Department of Nephrology, IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid; Fundacion Renal Iñigo Alvarez de Toledo-IRSIN and REDINREN, Av Reyes Católicos 2, 28040 Madrid, Spain
Authors to whom correspondence should be addressed.
Academic Editor: Raymond Vanholder
Received: 9 January 2017 / Revised: 13 March 2017 / Accepted: 16 March 2017 / Published: 23 March 2017
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
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Chronic kidney disease is among the fastest growing causes of death worldwide. An increased risk of all-cause and cardiovascular death is thought to depend on the accumulation of uremic toxins when glomerular filtration rate falls. In addition, the circulating levels of several markers of inflammation predict mortality in patients with chronic kidney disease. Indeed, a number of cytokines are listed in databases of uremic toxins and uremic retention solutes. They include inflammatory cytokines (IL-1β, IL-18, IL-6, TNFα), chemokines (IL-8), and adipokines (adiponectin, leptin and resistin), as well as anti-inflammatory cytokines (IL-10). We now critically review the cytokines that may be considered uremic toxins. We discuss the rationale to consider them uremic toxins (mechanisms underlying the increased serum levels and evidence supporting their contribution to CKD manifestations), identify gaps in knowledge, discuss potential therapeutic implications to be tested in clinical trials in order to make this knowledge useful for the practicing physician, and identify additional cytokines, cytokine receptors and chemokines that may fulfill the criteria to be considered uremic toxins, such as sIL-6R, sTNFR1, sTNFR2, IL-2, CXCL12, CX3CL1 and others. In addition, we suggest that IL-10, leptin, adiponectin and resistin should not be considered uremic toxins toxins based on insufficient or contradictory evidence of an association with adverse outcomes in humans or preclinical data not consistent with a causal association. View Full-Text
Keywords: chronic kidney disease; inflammation; uremic toxins; adipokines; chemokines; decoy receptor; mortality chronic kidney disease; inflammation; uremic toxins; adipokines; chemokines; decoy receptor; mortality

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Castillo-Rodríguez, E.; Pizarro-Sánchez, S.; Sanz, A.B.; Ramos, A.M.; Sanchez-Niño, M.D.; Martin-Cleary, C.; Fernandez-Fernandez, B.; Ortiz, A. Inflammatory Cytokines as Uremic Toxins: “Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son”. Toxins 2017, 9, 114.

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