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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1469353
This article is part of the Research Topic Immunological Aspects of Fibrosis Pathogenesis: Novel Mechanisms and Therapeutic Strategies View all 4 articles

Transition from acute kidney injury to chronic kidney disease in a long-term murine model of Shiga toxin-induced hemolytic-uremic syndrome

Provisionally accepted
Jamila Wegener Jamila Wegener 1,2Sophie Dennhardt Sophie Dennhardt 1,2Ivonne Löffler Ivonne Löffler 3Sina M. Coldewey Sina M. Coldewey 1,2,4*
  • 1 Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
  • 2 Septomics Research Center, Jena University Hospital, Jena, Germany
  • 3 Department of Internal Medicine III, Jena University Hospital, Jena, Germany
  • 4 Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany

The final, formatted version of the article will be published soon.

    Up to 40 % of patients with typical hemolytic-uremic syndrome (HUS) characterized by microangiopathic hemolytic anemia and acute kidney injury (AKI), develop long-term consequences, most prominently chronic kidney disease (CKD). The transition from AKI to CKD, particular in the context of HUS, is not yet fully understood. The objective of this study was to establish and characterize a Shiga toxin (Stx)-induced long-term HUS model to facilitate the study of mechanisms underlying the AKI-to-CKD transition. C57BL/6 mice were subjected to 5, 10, 15 or 20 ng/kg Stx on day 0, 3 and 6 of the experiment and were sacrificed on day 14 or day 21 to identify the critical time of turn over from acute to chronic state of HUS disease. Acute disease, indicated by weight loss, plasma neutrophil gelatinase-associated lipocalin (NGAL) and urea, and renal neutrophils, diminished after 14 and returned to sham level after 21 days. HUS-associated hemolytic anemia transitioned to non-hemolytic microcytic anemia along with unchanged erythropoietin levels after 21 days. Renal cytokine levels indicated a shift towards pro-fibrotic signaling and interstitial fibrosis developed concentration-dependently after 21 days. While Stx induced the intrarenal invasion of proinflammatory M1 and pro-fibrotic M2 macrophages after 14 days, pro-fibrotic M2 macrophages were the dominant phenotype after 21 days. In conclusion, we established and characterized the first Stxinduced long-term model of HUS. This tool facilitates the study of underlying mechanisms in the early AKI-to-CKD transition following HUS and allows the testing of compounds that may protect patients with AKI from developing subsequent CKD.

    Keywords: Chronic Kidney Disease, Acute Kidney Injury, animal model, Fibrosis, Anemia, Hemolytic-Uremic Syndrome

    Received: 23 Jul 2024; Accepted: 05 Sep 2024.

    Copyright: © 2024 Wegener, Dennhardt, Löffler and Coldewey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sina M. Coldewey, Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany

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