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

• Conditions: Renal Function Disorder

• Registration Number: NCT02061566
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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.

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.

Study Timeline

• Status Verified: 2014-02
• Study Start: 2014-02
• Study First Submitted: 2014-02-11
• Study First Submitted QC: 2014-02-11
• Study First Posted: 2014-02-13
• Last Update Submitted: 2014-02-23
• Last Update Posted: 2014-02-25
• Primary Completion: 2014-12
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• ICU patients

Exclusion Criteria

• Less than 20 years old

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Renal function recovery (BUN, Cre)	1 month

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan