Winnie Chan1, Jos A Bosch2, Anna C Phillips3, Shui Hao Chin4, Adaikala Antonysunil5, Nicholas Inston6, Sue Moore6, Okdeep Kaur7, Philip G McTernan8, Richard Borrows9. 1. Department of Nephrology & Kidney Transplantation, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham, UK; Department of Nutrition & Dietetics, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK. 2. School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham, UK; Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands. 3. School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, Birmingham, UK. 4. Department of Cardiovascular Sciences, Clinical Sciences Wing, University of Leicester, Glenfield Hospital, Leicester, UK. 5. Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK. 6. Department of Nephrology & Kidney Transplantation, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK. 7. Imperial Centre for Translational and Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK. 8. Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK. Electronic address: P.G.McTernan@warwick.ac.uk. 9. Department of Nephrology & Kidney Transplantation, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK; Centre for Translational Inflammation Research, University of Birmingham, Edgbaston, Birmingham, UK. Electronic address: Richard.Borrows@uhb.nhs.uk.
Abstract
OBJECTIVE: Cardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored. DESIGN AND METHODS: This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs. MAIN OUTCOME MEASURES: Demographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected. RESULTS: Endotoxemia (P = .03), reduced 25-hydroxyvitamin D (P = .04), high fructose intake (P < .001), decreased fiber intake (P < .001), and abdominal obesity (P = .002) were independently associated with elevated hsCRP. In turn, endotoxemia (P = .007) and increasing hsCRP (P = .02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P = .02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P < .001), hypertriglyceridemia (P < .001), increased fructose intake (P = .01), and abdominal obesity (P = .01). CONCLUSIONS: Endotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets.
OBJECTIVE:Cardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored. DESIGN AND METHODS: This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs. MAIN OUTCOME MEASURES: Demographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected. RESULTS:Endotoxemia (P = .03), reduced 25-hydroxyvitamin D (P = .04), high fructose intake (P < .001), decreased fiber intake (P < .001), and abdominal obesity (P = .002) were independently associated with elevated hsCRP. In turn, endotoxemia (P = .007) and increasing hsCRP (P = .02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P = .02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P < .001), hypertriglyceridemia (P < .001), increased fructose intake (P = .01), and abdominal obesity (P = .01). CONCLUSIONS:Endotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets.
Authors: Nasser M Al-Daghri; Saba Abdi; Shaun Sabico; Abdullah M Alnaami; Kaiser A Wani; Mohammed G A Ansari; Malak Nawaz Khan Khattak; Nasiruddin Khan; Gyanendra Tripathi; George P Chrousos; Philip G McTernan Journal: Biomolecules Date: 2021-11-14
Authors: George A Kaysen; Xiaoling Ye; Jochen G Raimann; Yuedong Wang; Alice Topping; Len A Usvyat; Stefano Stuard; Bernard Canaud; Frank M van der Sande; Jeroen P Kooman; Peter Kotanko Journal: J Lipid Res Date: 2018-06-12 Impact factor: 5.922