DEVELOPMENT AND TESTING OF BIOMARKERS FOR RENAL ALLOGRAFT FIBROSIS

Overview

Status: Recruiting
Keywords: nephrology , biomarker , specimen collection , tgfb , ctgf , post renal transplant
IRB Number: 00042194
Specialty: Nephrology and Hypertension
Sub Specialties: Kidney Transplant

Brief Summary

While renal allograft survival has improved in the early post-transplant period due to better immunosuppression, this has not translated into better long-term graft survival. Currently, serum creatinine is the primary marker used to follow graft function. However, serum creatinine is not specific and certainly not sensitive. As a result, significant graft dysfunction is necessary to cause serum creatinine elevations and to trigger a renal transplant biopsy. There is a need to develop new, more sensitive and specific biomarkers of renal allograft dysfunction and fibrosis. Development of blood or urinary biomarkers that correlate with the histologic changes occurring within the allograft may also allow for testing the efficacy of specific therapeutic strategies early without the need for long-term follow-up. Our hypothesis is that, by developing specific fibrosis biomarkers, we will be able to identify surrogate markers for renal allograft fibrosis and correlate them with long-term outcome. Our prediction is that, by non-invasively identifying a specific genes signature, we can alter graft outcome and subsequent graft loss. The challenge that we will be undertaking is the validation of these fibrosis biomarkers in a larger patient population in order to facilitate the adoption of tests for disease detection and early management. This may also allow for the development of new therapeutic targets and drugs designed to influence long-term renal function.

Detailed Description

While renal allograft survival has improved in the early post-transplant period due to better immunosuppression, this has not translated into better long-term graft survival. Currently, serum creatinine is the primary marker used to follow graft function. However, serum creatinine is not specific and certainly not sensitive. As a result, significant graft dysfunction is necessary to cause serum creatinine elevations and to trigger a renal transplant biopsy. There is a need to develop new, more sensitive and specific biomarkers of renal allograft dysfunction and fibrosis. Development of blood or urinary biomarkers that correlate with the histologic changes occurring within the allograft may also allow for testing the efficacy of specific therapeutic strategies early without the need for long-term follow-up. Our hypothesis is that, by developing specific fibrosis biomarkers, we will be able to identify surrogate markers for renal allograft fibrosis and correlate them with long-term outcome. Our prediction is that, by non-invasively identifying a specific genes signature, we can alter graft outcome and subsequent graft loss. The challenge that we will be undertaking is the validation of these fibrosis biomarkers in a larger patient population in order to facilitate the adoption of tests for disease detection and early management. This may also allow for the development of new therapeutic targets and drugs designed to influence long-term renal function.

Principal Investigator: Fuad Shihab
Department: Nephrology
Co Investigator: Lonnie Smith
Co Investigator: Nicole Kenyon
Co Investigator: Crystal Truax

Contact Information

Name:Amber Lamph
Phone: 801-585-3845
Email: amber.lamph@hsc.utah.edu

Inclusion Criteria

Group #1
 
-Recipients of DeNovo renal transplant age 18 and over who are not pregnant or breastfeeding.
 

 
Group #2
 
-Recipients of DeNovo renal transplant age 18 and over who are not pregnant or breastfeeding.
 
-Renal transplant recipient scheduled for a allograft biopsy, who have not enrolled in groups #1 or #3.
 

 
Group #3
 
-Recipients of DeNovo renal transplant age 18 and over who are not pregnant or breastfeeding.
 
-P/C ratio of >0.5 within last 6 months, or urine protein >/= 2+, or urine protein >/= 60 mg/dL within the last 6 months

Exclusion Criteria

Group #1
 
-Women who are pregnant or breastfeeding
 
-Individuals who are unable to provide written informed consent
 
-Individuals who are unwilling to comply with study visit schedule and procedures
 

 
Group #2
 
-Women who are pregnant or breastfeeding
 
-Individuals who are unable to provide written informed consent
 
-Individuals who are unwilling to comply with study visit schedule and procedures
 

 
Group #3
 
-Women who are pregnant or breastfeeding
 
-Individuals who are unable to provide written informed consent
 
-Individuals who are unwilling to comply with study visit schedule and procedures
 
-Individuals with a p/c ratio < 0.5 mg/dL, or urine protein < 2+, or urine protein < 60 mg/dL