BACKGROUND: Inflammatory processes play an important role for the progression of atherosclerosis. This can be studied particularly well in patients with chronic renal failure who are on hemodialysis, as they show systemic inflammation due to uremia and dialysis while suffering from premature mortality secondary to rapidly progressing atherosclerosis. Interleukin (IL)-10 is a regulatory cytokine that limits inflammatory processes. The quantitative production of IL-10 is subject to genetic variation based on polymorphisms in the promoter of its gene. We tested the hypothesis that the IL-10 genotype, by influencing the capacity to compensate for dialysis-induced systemic inflammation, determines the risk for cardiovascular complications. METHODS: Three hundred chronic hemodialysis patients were genotyped for the polymorphic bases at positions -1082 and -819 of the IL-10 promoter sequence. They were prospectively followed for a mean of 20.2 +/- 7.3 months. End-points of the study were major events related to cardiac, cerebrovascular or peripheral artery disease. RESULTS: The -1082A* allele, which is associated with low production of the cytokine IL-10 and elevated markers of systemic inflammation such as C reactive protein, was predictive for a higher cardiovascular morbidity (relative risk for cardiovascular events 2.76, 95% confidence interval 1.31 to 4.17, P = 0.004) compared to the -1082G* genotype. CONCLUSION: The IL-10 genotype influences the risk for cardiovascular events in hemodialysis patients and allows the definition of a high risk group. The data provide further evidence for a causal role of systemic inflammation for progressive atherosclerosis in dialysis patients.
BACKGROUND: Inflammatory processes play an important role for the progression of atherosclerosis. This can be studied particularly well in patients with chronic renal failure who are on hemodialysis, as they show systemic inflammation due to uremia and dialysis while suffering from premature mortality secondary to rapidly progressing atherosclerosis. Interleukin (IL)-10 is a regulatory cytokine that limits inflammatory processes. The quantitative production of IL-10 is subject to genetic variation based on polymorphisms in the promoter of its gene. We tested the hypothesis that the IL-10 genotype, by influencing the capacity to compensate for dialysis-induced systemic inflammation, determines the risk for cardiovascular complications. METHODS: Three hundred chronic hemodialysis patients were genotyped for the polymorphic bases at positions -1082 and -819 of the IL-10 promoter sequence. They were prospectively followed for a mean of 20.2 +/- 7.3 months. End-points of the study were major events related to cardiac, cerebrovascular or peripheral artery disease. RESULTS: The -1082A* allele, which is associated with low production of the cytokine IL-10 and elevated markers of systemic inflammation such as C reactive protein, was predictive for a higher cardiovascular morbidity (relative risk for cardiovascular events 2.76, 95% confidence interval 1.31 to 4.17, P = 0.004) compared to the -1082G* genotype. CONCLUSION: The IL-10 genotype influences the risk for cardiovascular events in hemodialysis patients and allows the definition of a high risk group. The data provide further evidence for a causal role of systemic inflammation for progressive atherosclerosis in dialysis patients.
Authors: William R Zhang; Amit X Garg; Steven G Coca; Philip J Devereaux; John Eikelboom; Peter Kavsak; Eric McArthur; Heather Thiessen-Philbrook; Colleen Shortt; Michael Shlipak; Richard Whitlock; Chirag R Parikh Journal: J Am Soc Nephrol Date: 2015-04-08 Impact factor: 10.121
Authors: João L Viana; George C Kosmadakis; Emma L Watson; Alan Bevington; John Feehally; Nicolette C Bishop; Alice C Smith Journal: J Am Soc Nephrol Date: 2014-04-03 Impact factor: 10.121
Authors: P-T Brinkkoetter; S Marinaki; U Gottmann; S Fleckenstein; C Stump; F J Van Der Woude; C Braun; B A Yard Journal: Clin Exp Immunol Date: 2005-03 Impact factor: 4.330
Authors: Alecsander F Bressan; Gisele A Fonseca; Rita C Tostes; R Clinton Webb; Victor Vitorino Lima; Fernanda Regina Giachini Journal: Fundam Clin Pharmacol Date: 2018-09-07 Impact factor: 2.748