Clinical trial NCT03317925: Renal Transplant Injury and the Renin-Angiotensin System in Kids (RETASK)
Official title: Renal Transplant Injury and the Renin-Angiotensin System in Kids (RETASK)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Renal Transplant
Renin-Angiotensin System
Rejection Acute Renal
Rejection Chronic Renal
Rejection of Renal Transplant
Keywords: Pediatric Renal Transplant
Renal Allograft
Angiotensin II
Angiotensin-(1-7)
ACE
ACE2
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Stanford University
First posted: 2017-10-23
Enrollment: 29
Sex: ALL
Minimum age (years): 1
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is an observational study with a convenience sample of patients recruited from Lucile Packard Children's Hospital kidney transplant evaluation clinic.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Acute graft injury
timeFrame: Within six months after kidney transplant
Secondary outcomes:
measure: Chronic graft damage
timeFrame: Six months after kidney transplant
measure: Renal function
timeFrame: Within six months after kidney transplant
measure: Proteinuria
timeFrame: Within six months after kidney transplant
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Andrew M South, MD MS
role: PRINCIPAL_INVESTIGATOR
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