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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Rejection Chronic Renal, Rejection of Renal Transplant, Renal Transplant, Renin-Angiotensin System, Rejection Acute Renal

Intervention / Treatment
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* Procedure: Renal Transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Renal Transplantation|Kidney transplantation and biomarkers that can identify injury after transplant.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute graft injury | Renal biopsy-confirmed acute renal allograft injury as determined by a pathologist (binary yes or no) | Within six months after kidney transplant | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACE, Pediatric Renal Transplant, Renal Allograft, Angiotensin II, Angiotensin-(1-7), ACE2