Clinical trial NCT03870542: Multicenter, Prospective Study for Urinary Exosomal Biomarkers of Kidney Allograft Tubulointerstitial Fibrosis
Official title: Multicenter, Prospective Observational Study to Identify and Validate a Composite of Urinary Exosomal Biomarkers for Kidney Allograft Tubulointerstitial Fibrosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Renal Fibrosis
Kidney Transplant Failure
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Korea University Anam Hospital
name: Inje University
name: Ulsan University Hospital
name: Hallym University Medical Center
First posted: 2019-03-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: kidney fibrosis
timeFrame: zero-day (time of transplant)
Secondary outcomes:
measure: Kidney graft function
timeFrame: 6 months and 1 year post-transplant
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Sung Shin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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. doi: 10.1056/NEJM200103293441301.
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.