Multicenter, Prospective Study for Urinary Exosomal Biomarkers of Kidney Allograft Tubulointerstitial Fibrosis

Study Overview
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Brief Summary
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The investigators aim to identify urinary exosomal biomarkers that represent the extent of graft fibrosis from deceased donor kidney transplantation. Urinary samples will be collected from deceased kidney donors at the time of procurement and zero-day kidney graft biopsy will be performed at the time of transplant. The association between urinary exosomes and the degree of graft fibrosis will be analyzed to identify biomarkers that represent fibrosis. The correlation between these biomarkers and graft long term outcomes will be investigated.

Detailed Description
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Interstitial fibrosis and tubular atrophy (IFTA), previously known as chronic allograft nephropathy (CAN), is diagnosed by pathologic changes involving all parts of the renal parenchyma and is one of the factors impacting graft survival and outcome. Currently, there is no standard to predict allograft fibrosis status at the time of procurement. Noninvasive biomarkers are necessary to monitor allograft status and to predict long-term outcomes. The investigators aim to conduct a multicenter prospective study to identify urinary exosomal biomarkers that represent the extent of graft fibrosis from deceased donor kidney transplantation. Urinary samples will be collected from deceased kidney donors at the time of procurement and zero-day kidney graft biopsy will be performed at the time of transplant. The zero-day biopsy tissue will be stained with Masson's Trichrome staining, Collagen I, III, IV immunostaining to evaluate the degree of fibrosis. Also, by ultracentrifuge, we will extract urinary exosomes and perform proteomics analysis and RNA-sequencing. The association between urinary exosomes and the degree of graft fibrosis will be analyzed to identify biomarkers that represent fibrosis. The correlation between these biomarkers and graft long term outcomes will be investigated.

Official Title
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Multicenter, Prospective Observational Study to Identify and Validate a Composite of Urinary Exosomal Biomarkers for Kidney Allograft Tubulointerstitial Fibrosis

Conditions
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Renal Fibrosis, Kidney Transplant Failure

Intervention / Treatment
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* Procedure: kidney transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: end-stage renal disease patients receiving kidney transplantation from deceased donors who have the ability to provide content for this study Exclusion Criteria: multi-organ transplantation candidate or history of previous transplant, history of extra-renal solid organ or bone marrow or stem cell transplant, active infection, history of recent intoxication of alcohol or substance abuse within 24 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Deceased donor kidney transplantation<br>Patients receiving kidney transplants from deceased donor in the participating centers during the study period | Procedure: kidney transplantation<br>* Kidney transplant for end-stage renal disease from deceased kidney donors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| kidney fibrosis | the degree of kidney graft fibrosis on zero day biopsy | zero-day (time of transplant) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney graft function | Kidney graft function assessed with serum Creatinine, eGFR, CKD-EPI | 6 months and 1 year post-transplant |