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

Wake Forest University (WFU)

Status: Completed

Conditions: Rejection of Renal Transplant; Rejection Acute Renal; Renin-Angiotensin System; Rejection Chronic Renal; Renal Transplant

Treatments: Procedure: Renal Transplantation

Study type: Observational

Funder types: Other

Identifiers

NCT03317925

00046001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 29 patients

Sex: All

Ages: 1 to 20 years old

Volunteers: No 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

Exclusion criteria

• Transplanted at a center other than Lucile Packard Children's Hospital at Stanford

Trial design