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

Renal Transplant Clinical Trial

— RETASK  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03317925
• Other study ID #: 00046001
• Status: Completed
• Phase: N/A
• First received: October 18, 2017
• Last updated: November 6, 2017
• Start date: July 16, 2014
• Est. completion date: April 26, 2017

Study information

• Verified date: October 2017
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: April 26, 2017
• Est. primary completion date: January 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Rejection Acute Renal
• Rejection Chronic Renal
• Rejection of Renal Transplant
• Renal Transplant
• Renin-Angiotensin System

Intervention

Procedure:
• Renal Transplantation
Kidney transplantation and biomarkers that can identify injury after transplant.

Locations

Country	Name	City	State
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (45)

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Ling XB, Sigdel TK, Lau K, Ying L, Lau I, Schilling J, Sarwal MM. Integrative urinary peptidomics in renal transplantation identifies biomarkers for acute rejection. J Am Soc Nephrol. 2010 Apr;21(4):646-53. doi: 10.1681/ASN.2009080876. Epub 2010 Feb 11. — View Citation

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Numakura K, Satoh S, Tsuchiya N, Saito M, Maita S, Obara T, Tsuruta H, Inoue T, Narita S, Horikawa Y, Kagaya H, Miura M, Habuchi T. Hyperuricemia at 1 year after renal transplantation, its prevalence, associated factors, and graft survival. Transplantation. 2012 Jul 27;94(2):145-51. doi: 10.1097/TP.0b013e318254391b. — View Citation

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* Note: There are 45 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Renal function	Glomerular filtration rate by the Schwartz equation (mL/min/1.73 m^2)	Within six months after kidney transplant
Secondary	Proteinuria	Urine protein-to-creatinine ratio above 0.2 mg/mg creatinine	Within six months after kidney transplant