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Secondary Immunodeficiency Related to Kidney Disease (SIDKD)—Definition, Unmet Need, and Mechanisms

Stefanie Steiger, Jan Rossaint, Alexander Zarbock and Hans-Joachim Anders
JASN February 2022, 33 (2) 259-278; DOI: https://doi.org/10.1681/ASN.2021091257
Stefanie Steiger
1Division of Nephrology, Department of Medicine IV, Ludwig Maximilians University Hospital of Munich, Munich, Germany
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Jan Rossaint
2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany
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Alexander Zarbock
2Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany
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Hans-Joachim Anders
1Division of Nephrology, Department of Medicine IV, Ludwig Maximilians University Hospital of Munich, Munich, Germany
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Abstract

Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.

  • kidney disease
  • immunodeficiency
  • infection
  • chronic inflammation
  • Copyright © 2022 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 33 (2)
Journal of the American Society of Nephrology
Vol. 33, Issue 2
February 2022
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Secondary Immunodeficiency Related to Kidney Disease (SIDKD)—Definition, Unmet Need, and Mechanisms
Stefanie Steiger, Jan Rossaint, Alexander Zarbock, Hans-Joachim Anders
JASN Feb 2022, 33 (2) 259-278; DOI: 10.1681/ASN.2021091257

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Secondary Immunodeficiency Related to Kidney Disease (SIDKD)—Definition, Unmet Need, and Mechanisms
Stefanie Steiger, Jan Rossaint, Alexander Zarbock, Hans-Joachim Anders
JASN Feb 2022, 33 (2) 259-278; DOI: 10.1681/ASN.2021091257
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  • Article
    • Abstract
    • Toward a New and Uniform Definition of SIDKD
    • Epidemiology of SIDKD
    • Immunophenotype of Patients with Kidney Disease
    • Pathogenic Mechanisms of SIDKD
    • Summary and a Call for Action
    • Disclosures
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More in this TOC Section

  • High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity
  • Cost Barriers to More Widespread Use of Peritoneal Dialysis in the United States
  • Tissue Culture Models of AKI: From Tubule Cells to Human Kidney Organoids
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