Clinical trial NCT03487861: Urinary Transglutaminase 2 as a Biomarker for Kidney Allograft Fibrosis
Official title: Development of a Diagnostic Kit for Urinary Transglutaminase 2 as a Biomarker for Kidney Allograft Fibrosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Allograft Fibrosis
Kidney Transplant Failure and Rejection
Keywords: transglutaminase type 2
kidney transplantation
chronic allograft nephropathy
biomarker
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2018-04-04
Enrollment: 1000
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: PROBABILITY_SAMPLE
Study population: kidney transplant recipients from cadaveric or living donors

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: change of level of urinary transglutaminase 2
timeFrame: 3 days, 7 days, 1 month, 3 months, 6 months post-transplant
Secondary outcomes:
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: STUDY_CHAIR
References:
citation: Meguid El Nahas A, Bello AK. Chronic kidney disease: the global challenge. Lancet. 2005 Jan 22-28;365(9456):331-40. doi: 10.1016/S0140-6736(05)17789-7.
citation: Lorand L, Graham RM. Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol. 2003 Feb;4(2):140-56. doi: 10.1038/nrm1014.
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. 2011 Aug 1;208(8):1707-19. doi: 10.1084/jem.20101457. Epub 2011 Jul 11.
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. doi: 10.1083/jcb.121.2.439.
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. doi: 10.1074/jbc.M109.012948. Epub 2009 Apr 27.
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/ASN.2013050563. Epub 2013 Dec 19.
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. doi: 10.1016/j.jhep.2005.12.025. Epub 2006 Feb 8.
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.
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. doi: 10.4049/jimmunol.1500651. Epub 2015 Oct 9.
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. doi: 10.1002/eji.201445177. Epub 2015 Jan 21.
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. doi: 10.4161/oxim.1.1.6491.
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 1.
citation: 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(11):1136-46. doi: 10.1097/TP.0b013e31824ef181.
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.