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Therapeutics targeting persistent inflammation in chronic kidney disease

  • Anna Machowska
    Affiliations
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
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  • Juan Jesus Carrero
    Affiliations
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
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  • Bengt Lindholm
    Affiliations
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
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  • Peter Stenvinkel
    Correspondence
    Reprint requests: Peter Stenvinkel, Department of Renal Medicine, M99, Karolinska University Hospital at Huddinge, 141 86 Stockholm, Sweden
    Affiliations
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
    Search for articles by this author
      Systemic inflammation is a condition intrinsically linked to chronic kidney disease (CKD) and its other typical sequelae, such as acquired immune dysfunction, protein-energy wasting (PEW), and accelerated vascular aging that promote premature cardiovascular disease (CVD) and infections, the two leading causes of death in CKD patients. Inflammation is a major contributor to complications in CKD, and inflammatory markers, such as C-reactive protein and pro- and anti-inflammatory cytokines, correlate with underlying causes and consequences of the inflamed uremic phenotype, such as oxidative stress, endothelial dysfunction, CVD, PEW, and infections, and are sensitive and independent predictors of outcome in CKD. Therefore, inflammation appears to be a logical target for potential preventive and therapeutic interventions in patients with CKD. Putative anti-inflammatory therapy strategies aiming at preventing complications and improving outcomes in CKD span over several areas: (1) dealing with the source of inflammation (such as cardiovascular, gastrointestinal or periodontal disease and depression); (2) providing nonspecific immune modulatory effects by promoting healthy dietary habits and other lifestyle changes; (3) promoting increased use of recognized pharmacologic interventions that have pleiotropic effects; and, (4) introducing novel targeted anticytokine interventions. This review provides a brief update on inflammatory biomarkers and possible therapeutic approaches targeting inflammation and the uremic inflammatory milieu in patients with CKD.

      Abbreviations:

      CKD (chronic kidney disease), CRP (C-reactive protein), CV (cardiovascular), CVD (cardiovascular disease), ESRD (end-stage renal disease), HD (hemodialysis), hsCRP (high-sensitivity C-reactive protein), IL-1 (interleukin- 1), IL-6 (interleukin-6), IL-10 (interleukin-10), LPS (lipopolysaccharide), MIA (malnutrition, inflammation, atherosclerosis), Nrf2 (nuclear factor erythroid 2–related factor), PD (peritoneal dialysis), PEW (protein-energy wasting), PTX3 (pentraxin-3), PUFA (polyunsaturated fatty acid), RCT (randomized controlled trial), SFA (saturated fatty acid), TNF (tumor necrosis factor), TWEAK (TNF-like weak inducer of apoptosis)
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