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Sökning: WFRF:(Siegel KR)

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  • Banerjee, T, et al. (författare)
  • Dietary Factors and Prevention: Risk of End-Stage Kidney Disease by Fruit and Vegetable Consumption
  • 2021
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 52:5, s. 356-367
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> The association between fruit and vegetable (FV) intake and the risk of end-stage kidney disease (ESKD) has not been examined in the general population and fully explored in chronic kidney disease (CKD). We prospectively evaluated this relationship in US representative sample of adults and evaluated consistency by the presence or absence, and severity, of CKD. <b><i>Methods:</i></b> We used data from the Third National Health and Nutrition Examination Survey (1988–1994) linked with the US Renal Data System, including 14,725 adults aged ≥20 years and with follow-up for ESKD through 2008. Daily FV intake was ascertained using a food frequency questionnaire. We examined the association between selected categories of FV intake and ESKD using a Fine Gray competing risk model adjusting for sociodemographics, lifestyle, clinical and nutritional factors, estimated glomerular filtration rate, and albuminuria. We evaluated whether risk varied in individuals with severe versus any CKD. <b><i>Results:</i></b> 230 participants (1.5%) developed ESKD during follow-up. In the adjusted model, compared to highest intake, those in lowest categories of FV intake had a higher risk of ESKD, for &#x3c;2 times/day (1.45 [1.24–1.68], 2 to &#x3c;3 times/day (1.40 [1.18–1.61]), 3 to &#x3c;4 times/day (1.25 [1.04–1.46]), and 4 to &#x3c;6 times/day (1.14 [0.97–1.31]). There was suggestion of heterogeneity (<i>p</i> for interaction = 0.03) with possible stronger inverse association in patients with CKD than those without CKD. After stratification, we obtained similar strong inverse association when we examined ESKD incidence across intake of FVs in participants with CKD stages 1–4 (<i>n</i> = 5,346) and specifically in those with CKD stages 3–4 (<i>n</i> = 1,084). <b><i>Conclusions:</i></b> Low intake of FVs was associated with higher risk of ESKD in US adults with and without CKD, supporting an emerging body of literature on the potential benefits of plant-rich diets for prevention of ESKD.
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  • Jing, CZ, et al. (författare)
  • Macrophage metabolic reprogramming presents a therapeutic target in lupus nephritis
  • 2020
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:26, s. 15160-15171
  • Tidskriftsartikel (refereegranskat)abstract
    • IgG antibodies cause inflammation and organ damage in autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the metabolic profile of macrophages isolated from inflamed tissues in immune complex (IC)-associated diseases, including SLE and rheumatoid arthritis, and following IgG Fcγ receptor cross-linking. We found that human and mouse macrophages undergo a switch to glycolysis in response to IgG IC stimulation, mirroring macrophage metabolic changes in inflamed tissue in vivo. This metabolic reprogramming was required to generate a number of proinflammatory mediators, including IL-1β, and was dependent on mTOR and hypoxia-inducible factor (HIF)1α. Inhibition of glycolysis, or genetic depletion of HIF1α, attenuated IgG IC-induced activation of macrophages in vitro, including primary human kidney macrophages. In vivo, glycolysis inhibition led to a reduction in kidney macrophage IL-1β and reduced neutrophil recruitment in a murine model of antibody-mediated nephritis. Together, our data reveal the molecular mechanisms underpinning FcγR-mediated metabolic reprogramming in macrophages and suggest a therapeutic strategy for autoantibody-induced inflammation, including lupus nephritis.
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