Rejection Acute Renal, Rejection Chronic Renal, Rejection of Renal Transplant, Renal Transplant, Renin-Angiotensin System
Conditions
Keywords
Pediatric Renal Transplant, Renal Allograft, Angiotensin II, Angiotensin-(1-7), ACE, ACE2
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.
Interventions
PROCEDURERenal Transplantation
Kidney transplantation and biomarkers that can identify injury after transplant.
Sponsors
Stanford University
Wake Forest University Health Sciences
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 20 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed