Urinary Transglutaminase 2 as a Biomarker for Kidney Allograft Fibrosis

Kidney Transplant Failure and Rejection Clinical Trial

Official title:

Development of a Diagnostic Kit for Urinary Transglutaminase 2 as a Biomarker for Kidney Allograft Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03487861
• Other study ID #: NRF-2016M3A9E8941330
• Status: Recruiting
• First received: March 18, 2018
• Last updated: April 3, 2018
• Start date: August 29, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2018
• 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 aim of this study is to verify the ability of transglutaminase type 2 to predict rejection or chronic allograft nephropathy of renal allograft. On the basis of biomolecular mechanisms aggravating chronic allograft nephropathy, we eventually expect to develop the remedy to prevent chronic allograft nephropathy after kidney transplantation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• kidney transplant recipients from cadaveric or living donors

• kidney transplant recipients who take immunosuppressants regularly

• kidney transplant recipients who voluntarily agree to participate in this trial

Exclusion Criteria:

• multiorgan transplant recipients

• kidney transplant recipients with active infection

• kidney transplant recipients with alcohol or drug addiction

Related Conditions & MeSH terms

• Fibrosis
• Kidney Allograft Fibrosis
• Kidney Transplant Failure and Rejection

Intervention

Diagnostic Test:
• observational(urinary biomarker for kidney allograft fibrosis)
After an informed consent is obtained, urine specimens will be collected prospectively before kidney transplantation (if available) and 3rd and 7th day, 1st, 3rd, and 6th month post-transplant. About 35~50ml of urine sample is collected from each patient. For each urine specimen, 0.5 ml of a protease inhibitor mixture (5mM 4-(2-animoethyl) benzensulfonyl fluoride hydrolchloride, 2 µM Leupeptin-hemisulfate, and 3.3 mM Sodium azide) is added. To remove urinary sediments including whole cells, large membrane particles, and other debris, urine specimens are centrifuged at a rate of 4000 rpm for 15 minutes at 4 ?. An aliquot of supernatant is stored at -80 ? until use. Urinary biomarkers including transglutaminase 2 are quantified using ELISA or CBA. In addition, urinary exosomes are isolated and analyzed. When a for-cause biopsy is done for some patients, the correlation between biomarkers and pathologic diagnosis will be assessed.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (14)

Anglicheau D, Muthukumar T, Hummel A, Ding R, Sharma VK, Dadhania D, Seshan SV, Schwartz JE, Suthanthiran M. Discovery and validation of a molecular signature for the noninvasive diagnosis of human renal allograft fibrosis. Transplantation. 2012 Jun 15;93 — View Citation

Breggia AC, Himmelfarb J. Primary mouse renal tubular epithelial cells have variable injury tolerance to ischemic and chemical mediators of oxidative stress. Oxid Med Cell Longev. 2008 Oct-Dec;1(1):33-8. — View Citation

Brusilovsky M, Radinsky O, Cohen L, Yossef R, Shemesh A, Braiman A, Mandelboim O, Campbell KS, Porgador A. Regulation of natural cytotoxicity receptors by heparan sulfate proteoglycans in -cis: A lesson from NKp44. Eur J Immunol. 2015 Apr;45(4):1180-91. d — View Citation

Halloran PF, Famulski KS, Reeve J. Molecular assessment of disease states in kidney transplant biopsy samples. Nat Rev Nephrol. 2016 Sep;12(9):534-48. doi: 10.1038/nrneph.2016.85. Epub 2016 Jun 27. Review. — View Citation

Jeong EM, Kim CW, Cho SY, Jang GY, Shin DM, Jeon JH, Kim IG. Degradation of transglutaminase 2 by calcium-mediated ubiquitination responding to high oxidative stress. FEBS Lett. 2009 Feb 18;583(4):648-54. doi: 10.1016/j.febslet.2009.01.032. Epub 2009 Feb — View Citation

Kojima S, Nara K, Rifkin DB. Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells. J Cell Biol. 1993 Apr;121(2):439-48. — View Citation

Lorand L, Graham RM. Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol. 2003 Feb;4(2):140-56. Review. — View Citation

Meguid El Nahas A, Bello AK. Chronic kidney disease: the global challenge. Lancet. 2005 Jan 22-28;365(9456):331-40. Review. — View Citation

Melhem A, Muhanna N, Bishara A, Alvarez CE, Ilan Y, Bishara T, Horani A, Nassar M, Friedman SL, Safadi R. Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC. J Hepatol. 2006 Jul;45(1):60-71. Epub 2006 Feb 8. — View Citation

Oh K, Park HB, Byoun OJ, Shin DM, Jeong EM, Kim YW, Kim YS, Melino G, Kim IG, Lee DS. Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice. J Exp Med. 201 — View Citation

Scarpellini A, Germack R, Lortat-Jacob H, Muramatsu T, Billett E, Johnson T, Verderio EA. Heparan sulfate proteoglycans are receptors for the cell-surface trafficking and biological activity of transglutaminase-2. J Biol Chem. 2009 Jul 3;284(27):18411-23. — View Citation

Scarpellini A, Huang L, Burhan I, Schroeder N, Funck M, Johnson TS, Verderio EA. Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis. J Am Soc Nephrol. 2014 May;25(5):1013-27. doi: 10.1681 — View Citation

Shin S, Kim YH, Cho YM, Park Y, Han S, Choi BH, Choi JY, Han DJ. Interpreting CD56+ and CD163+ infiltrates in early versus late renal transplant biopsies. Am J Nephrol. 2015;41(4-5):362-9. doi: 10.1159/000430473. Epub 2015 Jun 18. — View Citation

Victorino F, Sojka DK, Brodsky KS, McNamee EN, Masterson JC, Homann D, Yokoyama WM, Eltzschig HK, Clambey ET. Tissue-Resident NK Cells Mediate Ischemic Kidney Injury and Are Not Depleted by Anti-Asialo-GM1 Antibody. J Immunol. 2015 Nov 15;195(10):4973-85. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change of level of urinary transglutaminase 2		3 days, 7 days, 1 month, 3 months, 6 months post-transplant