PMID- 30249039 OWN - NLM STAT- MEDLINE DCOM- 20190909 LR - 20190909 IS - 2072-6651 (Electronic) IS - 2072-6651 (Linking) VI - 10 IP - 10 DP - 2018 Sep 23 TI - The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease. LID - 10.3390/toxins10100384 [doi] LID - 384 AB - Uremic toxin (UT) retention in chronic kidney disease (CKD) affects biological systems. We aimed to identify the associations between UT, inflammatory biomarkers and biomarkers of the uremic cardiovascular response (BUCVR) and their impact on cardiovascular status as well as their roles as predictors of outcome in CKD patients. CKD patients stages 3, 4 and 5 (n = 67) were recruited and UT (indoxyl sulfate/IS, p-cresil sulfate/pCS and indole-3-acetic acid/IAA); inflammatory biomarkers [Interleukin-6 (IL-6), high sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble Fas (sFas)] and BUCVRs [soluble CD36 (sCD36), soluble receptor for advanced glycation end products (sRAGE), fractalkine] was measured. Patients were followed for 5.2 years and all causes of death was used as the primary outcome. Artery segments collected at the moment of transplantation were used for the immunohistochemistry analysis in a separate cohort. Estimated glomerular filtration rate (eGFR), circulating UT, plasma biomarkers of systemic and vascular inflammation and BUCVR were strongly interrelated. Patients with plaque presented higher signs of UT-induced inflammation and arteries from CKD patients presented higher fractalkine receptor (CX3CR1) tissue expression. Circulating IS (p = 0.03), pCS (p = 0.007), IL-6 (p = 0.026), sFas (p = 0.001), sCD36 (p = 0.01) and fractalkine (p = 0.02) were independent predictors of total mortality risk in CKD patients. Our results reinforce the important role of uremic toxicity in the pathogenesis of cardiovascular disease (CVD) in CKD patients through an inflammatory pathway. FAU - Claro, Ligia Maria AU - Claro LM AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. lmclaro@gmail.com. FAU - Moreno-Amaral, Andrea N AU - Moreno-Amaral AN AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. deamoreno@gmail.com. FAU - Gadotti, Ana Carolina AU - Gadotti AC AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. ana_raixu3@hotmail.com. FAU - Dolenga, Carla J AU - Dolenga CJ AD - Basic Pathology Department, Universidade Federal do Parana, Curitiba, PR 80050-540, Brazil. carla.vet10@gmail.com. FAU - Nakao, Lia S AU - Nakao LS AD - Basic Pathology Department, Universidade Federal do Parana, Curitiba, PR 80050-540, Brazil. lia.nakao@ufpr.br. FAU - Azevedo, Marina L V AU - Azevedo MLV AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. malu_tu@yahoo.com.br. FAU - de Noronha, Lucia AU - de Noronha L AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. lnno.noronha@gmail.com. FAU - Olandoski, Marcia AU - Olandoski M AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. bio.estatistica@pucpr.br. FAU - de Moraes, Thyago P AU - de Moraes TP AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. thyago.moraes@pucpr.br. FAU - Stinghen, Andrea E M AU - Stinghen AEM AUID- ORCID: 0000-0001-8595-5321 AD - Basic Pathology Department, Universidade Federal do Parana, Curitiba, PR 80050-540, Brazil. andreastinghen@ufpr.br. FAU - Pecoits-Filho, Roberto AU - Pecoits-Filho R AD - Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, PR 80215-901, Brazil. r.pecoits@pucpr.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180923 PL - Switzerland TA - Toxins (Basel) JT - Toxins JID - 101530765 RN - 0 (Biomarkers) RN - 0 (CD36 Antigens) RN - 0 (CD36 protein, human) RN - 0 (Cresols) RN - 0 (Cytokines) RN - 0 (Indoleacetic Acids) RN - 0 (Sulfuric Acid Esters) RN - 0 (Toxins, Biological) RN - 56M34ZQY1S (4-cresol sulfate) RN - 6U1S09C61L (indoleacetic acid) RN - N187WK1Y1J (Indican) SB - IM MH - Adult MH - Aged MH - Biomarkers/metabolism MH - CD36 Antigens/metabolism MH - Cardiovascular Diseases/*metabolism/physiopathology MH - Cresols/*blood MH - Cytokines/metabolism MH - Female MH - Glomerular Filtration Rate MH - Humans MH - Indican/*blood MH - Indoleacetic Acids/*blood MH - Inflammation/*metabolism/physiopathology MH - Male MH - Middle Aged MH - Renal Artery/metabolism MH - Renal Insufficiency, Chronic/*metabolism/physiopathology MH - Sulfuric Acid Esters/*blood MH - Toxins, Biological/*blood MH - Uremia/*metabolism/physiopathology PMC - PMC6215310 OTO - NOTNLM OT - fractalkine (CX3CL1) OT - fractalkine receptor (CX3CR1) OT - inflammatory biomarkers OT - sCD36 OT - sRAGE OT - uremic toxins COIS- The authors declare no conflict of interest. EDAT- 2018/09/27 06:00 MHDA- 2019/09/10 06:00 PMCR- 2018/10/01 CRDT- 2018/09/26 06:00 PHST- 2018/08/24 00:00 [received] PHST- 2018/09/11 00:00 [revised] PHST- 2018/09/18 00:00 [accepted] PHST- 2018/09/26 06:00 [entrez] PHST- 2018/09/27 06:00 [pubmed] PHST- 2019/09/10 06:00 [medline] PHST- 2018/10/01 00:00 [pmc-release] AID - toxins10100384 [pii] AID - toxins-10-00384 [pii] AID - 10.3390/toxins10100384 [doi] PST - epublish SO - Toxins (Basel). 2018 Sep 23;10(10):384. doi: 10.3390/toxins10100384.