Indoxyl Sulfate Induces Leukocyte-endothelial Interactions Through Up-regulation of ICAM-1 in Acute Kidney Injury

Overview

Indoxyl sulfate (IS) is an anionic uremic toxin that is accumulated in the serum of patients with uremia. In previous study, the investigators successfully induced AKI animal model. IS enhanced intercellular adhesion molecule-1 (ICAM-1) expression in IL-1β-treated human umbilical vein endothelial cells (HUVECs) that this may play a critical role in the progression of AKI. However, the molecular mechanisms of ICAM-1 expression in IS-treated IL-1β-treated HUVECs need to be elucidated. HUVECs incubated with 0.2 or 1 mM IS for 24 h did not cause cytotoxicity. The IL-1β-induced ICAM-1 expression in HUVECs was significantly enhanced by IS pretreatment. Furthermore, the regulation of adhesion molecule expression involves a complex array of intracellular signaling pathways including mitogen-activated protein kinase (MAPKs), reactive oxygen species (ROS) and transcriptional factors. A better understanding of this might provide important insights into the prevention of AKI.

Full Title of Study: “National Taiwan University Hospital Yu-Lin Branch”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: December 2014

Detailed Description

Over the past decade, acute kidney injury (AKI) has acquired much attention because of their potentially devastating problems in clinical medicine. When kidneys lost their filtering function, a lot of dangerous metabolites were accumulated in the body, including urea, nitrogenous waste products and uremic toxins. Indoxyl sulfate (IS) is an anionic uremic toxin that is accumulated in the serum of patients with uremia. In previous study, the investigators successfully induced AKI animal model. IS enhanced intercellular adhesion molecule-1 (ICAM-1) expression in IL-1β-treated human umbilical vein endothelial cells (HUVECs) that this may play a critical role in the progression of AKI. However, the molecular mechanisms of ICAM-1 expression in IS-treated IL-1β-treated HUVECs need to be elucidated. HUVECs incubated with 0.2 or 1 mM IS for 24 h did not cause cytotoxicity. The IL-1β-induced ICAM-1 expression in HUVECs was significantly enhanced by IS pretreatment. Furthermore, the regulation of adhesion molecule expression involves a complex array of intracellular signaling pathways including mitogen-activated protein kinase (MAPKs), reactive oxygen species (ROS) and transcriptional factors. A better understanding of this might provide important insights into the prevention of AKI.

Arms, Groups and Cohorts

  • Acute kidney injury
    • Acute kidney injury in ICU
  • Non acute kidney injury
    • Non acute kidney injury

Clinical Trial Outcome Measures

Primary Measures

  • Renal function recovery (BUN, Cre)
    • Time Frame: 1 month

Participating in This Clinical Trial

Inclusion Criteria

  • ICU patients Exclusion Criteria:

  • Less than 20 years old

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Taiwan University Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Yu-Hsiang Chou, MD, Principal Investigator, NTUH Yun-Lin branch
  • Overall Contact(s)
    • Yu-Hsiang Chou, MD, +886-972655372, chouyuhsiang@yahoo.com.tw

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