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Original ArticlesClinical Nephrology
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IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD

Adriana M. Hung, Yohei Tsuchida, Kristen L. Nowak, Sudipa Sarkar, Michel Chonchol, Victoria Whitfield, Natjalie Salas, Anna Dikalova, Patricia G. Yancey, Jiansheng Huang, MacRae F. Linton, T. Alp Ikizler and Valentina Kon
CJASN May 2019, 14 (5) 702-711; DOI: https://doi.org/10.2215/CJN.04360418
Adriana M. Hung
Division of Nephrology, Tennessee Valley Healthcare System, Nashville, Tennessee;Department of Medicine and
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Yohei Tsuchida
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; and
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Kristen L. Nowak
Department of Medicine, University of Colorado Denver, Aurora, Colorado
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Sudipa Sarkar
Department of Medicine and
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Michel Chonchol
Department of Medicine, University of Colorado Denver, Aurora, Colorado
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Victoria Whitfield
Department of Medicine and
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Natjalie Salas
Department of Medicine and
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Anna Dikalova
Department of Medicine and
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Patricia G. Yancey
Department of Medicine and
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Jiansheng Huang
Department of Medicine and
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MacRae F. Linton
Department of Medicine and
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T. Alp Ikizler
Division of Nephrology, Tennessee Valley Healthcare System, Nashville, Tennessee;Department of Medicine and
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Valentina Kon
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; and
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Abstract

Background and objectives Systemic inflammation modulates cardiovascular disease risk and functionality of HDL in the setting of CKD. Whether interventions that modify systemic inflammation can improve HDL function in CKD is unknown.

Design, setting, participants, & measurements We conducted a post hoc analysis of two randomized, clinical trials, IL-1 trap in participants with GFR 15–59 ml/min per 1.73 m2 (study A) and IL-1 receptor antagonist in participants on maintenance hemodialysis (study B), to evaluate if IL-1 blockade had improved the anti-inflammatory activity (IL-6, TNF-α, and Nod-like receptor protein 3), antioxidant function (superoxide production), and net cholesterol efflux capacity of HDL. HDL function was measured using LPS-stimulated THP-1 macrophages or peritoneal macrophages of apoE-deficient mice exposed to the apoB-depleted, HDL-containing fraction obtained from the plasma of the study participants, collected before and after the interventions to block IL-1 effects. Analysis of covariance was used for between group comparisons.

Results The mean age of the participants was 60±13 years, 72% (n=33) were men, and 39% (n=18) were black. There were 32 CKD (16 IL-1 trap and 16 placebo) and 14 maintenance hemodialysis (7 IL-1 receptor antagonist and 7 placebo) participants. Compared with placebo, IL-1 inhibition, in study A and B reduced cellular expression of TNF-α by 15% (P=0.05) and 64% (P=0.02), IL-6 by 38% (P=0.004) and 56% (P=0.08), and Nod-like receptor protein 3 by 16% (P=0.01) and 25% (P=0.02), respectively. The intervention blunted superoxide production in the treated arm compared with placebo, with the values being higher by 17% in the placebo arm in study A (P<0.001) and 12% in the placebo arm in study B (P=0.004). Net cholesterol efflux capacity was not affected by either intervention.

Conclusions IL-1 blockade improves the anti-inflammatory and antioxidative properties of the HDL-containing fraction of plasma in patients with stages 3–5 CKD, including those on maintenance hemodialysis.

  • Chronic inflammation
  • HDL
  • IL-1 inhibition
  • CKD
  • IL6 protein, human
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Superoxides
  • Macrophages, Peritoneal
  • Tumor Necrosis Factor-alpha
  • macrophages
  • Lipoproteins, HDL
  • Anti-Inflammatory Agents
  • Inflammation
  • Renal Insufficiency, Chronic
  • dialysis
  • Oxidants
  • Cholesterol
  • Cardiovascular Diseases
  • NLR Proteins
  • Receptors, Interleukin-1
  • oxidative stress
  • Received April 6, 2018.
  • Accepted March 15, 2019.
  • Copyright © 2019 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 14 (5)
Clinical Journal of the American Society of Nephrology
Vol. 14, Issue 5
May 07, 2019
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IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD
Adriana M. Hung, Yohei Tsuchida, Kristen L. Nowak, Sudipa Sarkar, Michel Chonchol, Victoria Whitfield, Natjalie Salas, Anna Dikalova, Patricia G. Yancey, Jiansheng Huang, MacRae F. Linton, T. Alp Ikizler, Valentina Kon
CJASN May 2019, 14 (5) 702-711; DOI: 10.2215/CJN.04360418

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IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD
Adriana M. Hung, Yohei Tsuchida, Kristen L. Nowak, Sudipa Sarkar, Michel Chonchol, Victoria Whitfield, Natjalie Salas, Anna Dikalova, Patricia G. Yancey, Jiansheng Huang, MacRae F. Linton, T. Alp Ikizler, Valentina Kon
CJASN May 2019, 14 (5) 702-711; DOI: 10.2215/CJN.04360418
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More in this TOC Section

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  • Cardiovascular Safety and All-Cause Mortality of Methoxy Polyethylene Glycol-Epoetin Beta and Other Erythropoiesis-Stimulating Agents in Anemia of CKD
  • APOL1 Nephropathy Risk Alleles and Risk of Sepsis in Blacks
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Keywords

  • Chronic inflammation
  • HDL
  • IL-1 inhibition
  • CKD
  • IL6 protein, human
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Superoxides
  • Macrophages, Peritoneal
  • Tumor Necrosis Factor-alpha
  • macrophages
  • Lipoproteins, HDL
  • Anti-Inflammatory Agents
  • Inflammation
  • Renal Insufficiency, Chronic
  • dialysis
  • Oxidants
  • cholesterol
  • cardiovascular diseases
  • NLR Proteins
  • Receptors, Interleukin-1
  • oxidative stress

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