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

Kidney Transplant Failure Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03870542
• Other study ID #: S2019-0362-0001
• Status: Recruiting
• Start date: May 11, 2019
• Est. completion date: April 2022

Study information

• Verified date: September 2019
• Source: Asan Medical Center
• Contact: Sung Shin, MD, PhD
• Phone: 82-2-3010-3964
• Email: sshin[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Kidney Transplant Failure
• Renal Fibrosis

Intervention

Procedure:
• kidney transplantation
Kidney transplant for end-stage renal disease from deceased kidney donors

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (5)

Lead Sponsor	Collaborator
Asan Medical Center	Hallym University Medical Center, Inje University, Korea University Anam Hospital, Ulsan University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (5)

Gámez-Valero A, Lozano-Ramos SI, Bancu I, Lauzurica-Valdemoros R, Borràs 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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	kidney fibrosis	the degree of kidney graft fibrosis on zero day biopsy	zero-day (time of transplant)
Secondary	Kidney graft function	Kidney graft function assessed with serum Creatinine, eGFR, CKD-EPI	6 months and 1 year post-transplant