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

Renal Function Disorder Clinical Trial

Official title:

National Taiwan University Hospital Yu-Lin Branch

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02061566
• Other study ID #: 201310062RINA
• Status: Not yet recruiting
• Phase: N/A
• First received: February 11, 2014
• Last updated: February 23, 2014
• Start date: February 2014
• Est. completion date: December 2014

Study information

• Verified date: February 2014
• Source: National Taiwan University Hospital
• Contact: Yu-Hsiang Chou, MD
• Phone: +886-972655372
• Email: chouyuhsiang[@]yahoo.com.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 90 Years

Eligibility

Inclusion Criteria:

• ICU patients

Exclusion Criteria:

• Less than 20 years old

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Kidney Injury
• Renal Function Disorder
• Renal Insufficiency

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal function recovery (BUN, Cre)		1 month	No