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

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

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.

Study Overview

• Status: Unknown
• Conditions: Kidney Transplant Failure; Renal Fibrosis
• Intervention / Treatment: Procedure: kidney transplantation

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Contact: SUNG SHIN, Dr.; Email: sshin@amc.seoul.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

end-stage renal disease patients receiving kidney transplantation from deceased donors who have the ability to provide content for this study, patients willing to provide content and participate in this study during the follow-up period

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Deceased donor kidney transplantation; Patients receiving kidney transplants from deceased donor in the participating centers during the study period	Procedure: kidney transplantation; Kidney transplant for end-stage renal disease from deceased kidney donors

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Ulsan University Hospital; Korea University Anam Hospital; Inje University; Hallym University Medical Center
• Investigators: Principal Investigator: Sung Shin, MD, PhD, Asan Medical Center

Publications and helpful links

General Publications

• Singh T, Astor B, Zhong W, Mandelbrot D, Djamali A, Panzer S. Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides. Transplant Direct. 2017 Oct 18;3(11):e223. doi: 10.1097/TXD.0000000000000736. eCollection 2017 Nov.
• Hanssen O, Erpicum P, Lovinfosse P, Meunier P, Weekers L, Tshibanda L, Krzesinski JM, Hustinx R, Jouret F. Non-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients. Part I. In vivo imaging methods. Clin Kidney J. 2017 Feb;10(1):97-105. doi: 10.1093/ckj/sfw062. Epub 2016 Jul 28.
• Gamez-Valero A, Lozano-Ramos SI, Bancu I, Lauzurica-Valdemoros R, Borras FE. Urinary extracellular vesicles as source of biomarkers in kidney diseases. Front Immunol. 2015 Jan 30;6:6. doi: 10.3389/fimmu.2015.00006. eCollection 2015.
• Li B, Hartono C, Ding R, Sharma VK, Ramaswamy R, Qian B, Serur D, Mouradian J, Schwartz JE, Suthanthiran M. Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. N Engl J Med. 2001 Mar 29;344(13):947-54. doi: 10.1056/NEJM200103293441301.
• Gonzalez-Nolasco B, Wang M, Prunevieille A, Benichou G. Emerging role of exosomes in allorecognition and allograft rejection. Curr Opin Organ Transplant. 2018 Feb;23(1):22-27. doi: 10.1097/MOT.0000000000000489.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 11, 2019
• Primary Completion (ANTICIPATED): April 1, 2022
• Study Completion (ANTICIPATED): April 1, 2022

Study Registration Dates

• First Submitted: March 9, 2019
• First Submitted That Met QC Criteria: March 9, 2019
• First Posted (ACTUAL): March 12, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 24, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis
• Other Study ID Numbers: S2019-0362-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No