Renal Transplant Injury and the Renin-Angiotensin System in Kids (RETASK)

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT03317925

Collaborator

Stanford University (Other)

Enrollment

Location

33.3

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In pediatric kidney transplant patients, rejection, medication toxicity and ischemia cause early and chronic renal allograft injury, which reduces graft lifespan and patient survival. Early detection of injury would facilitate prevention and treatment. The gold standard surveillance biopsy has limitations including delayed discovery of injury. No noninvasive test identifies graft injury before it is clinically apparent. This project's goal is to develop a novel early marker of subclinical graft injury to facilitate prompt recognition and treatment.

Condition or Disease	Intervention/Treatment	Phase
Renal Transplant Renin-Angiotensin System Rejection Acute Renal Rejection Chronic Renal Rejection of Renal Transplant	Procedure: Renal Transplantation

Detailed Description

Kidney damage activates the traditional renin-angiotensin (Ang) system (RAS), characterized by Ang-converting enzyme (ACE)/Ang II/Ang II type 1 receptor. The Ang-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas pathway counteracts this damage. The balance, or ratio, between levels of the ACE/Ang II and ACE2/Ang-(1-7) pathways may be clinically important because Ang-(1-7) counteracts Ang II-mediated injury. An increase in ACE and Ang II expression and a decrease in ACE2 and Ang-(1-7) expression on tubular cells may promote renal injury. Tubular damage may increase urinary loss of protective ACE2 and Ang-(1-7), propagating renal damage by allowing ACE and Ang II to stimulate inflammation and fibrosis unopposed. The investigators hypothesis is that a shift in the urinary ACE-to-ACE2 and Ang II-to-Ang-(1-7) ratios towards ACE2 and Ang-(1-7) predicts acute graft injury diagnosed on renal biopsy and predicts chronic graft damage on renal biopsy.

Study Design

Study Type:

Observational

Actual Enrollment :

29 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Renal Transplant Injury and the Renin-Angiotensin System in Kids (RETASK)

Actual Study Start Date :

Jul 16, 2014

Actual Primary Completion Date :

Jan 20, 2016

Actual Study Completion Date :

Apr 26, 2017

Outcome Measures

Primary Outcome Measures

Acute graft injury [Within six months after kidney transplant]
Renal biopsy-confirmed acute renal allograft injury as determined by a pathologist (binary yes or no)

Secondary Outcome Measures

Chronic graft damage [Six months after kidney transplant]
Renal biopsy-confirmed chronic renal allograft damage as determined by a quantitative fibrosis pathology stain (percent fibrosis from 0 to 100%)
Renal function [Within six months after kidney transplant]
Glomerular filtration rate by the Schwartz equation (mL/min/1.73 m^2)
Proteinuria [Within six months after kidney transplant]
Urine protein-to-creatinine ratio above 0.2 mg/mg creatinine

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ages 1 - 20 years
Actively listed on the transplant list at Lucile Packard Children's Hospital at Stanford and received a renal transplant during the study enrollment period