Clinical trial NCT01315067: Diagnosis of Acute Rejection in Renal Transplant Patients by Urine Mass Spectrometry
Official title: Non-invasive Diagnosis of Acute Rejection in Renal Transplant Patients Using Mass Spectrometry of Urine Samples - a Multicentre Diagnostic Phase III Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rejection of Renal Transplant
Keywords: kidney transplantation
acute rejection
diagnosis
urine analysis
urinary peptides
mass spectrometry
allograft biopsy
pathology
diagnostic study
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2011-03-15
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a kidney or combined kidney/pancreas transplantation from several German transplant centres with an acute unexplained allograft dysfunction within the first year of transplantation who require a clinically indicated allograft biopsy

Brief summary: Reliable and timely detection of acute rejections in renal transplant patients is important to preserve the graft function and to prevent premature graft failure. The current gold standard for the rejection diagnosis is a renal biopsy which is usually performed upon an unexplained decline in the graft function (determined by serum creatinine or clearance). Because of the insensitivity of creatinine determinations and the invasiveness of renal biopsies, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry (MS) analysis of urine samples.

The ability of MS analysis to detect acute rejection has been demonstrated in small studies on selected patients but evidence is lacking that this test is efficacious in the routine setting of the post-transplant patient care. Based on our previous work that established urine peptide sets for acute rejection by MS, a prospective, multicentre diagnostic phase III study will be executed.

The aim of the study is to prove that this test is as equally effective as the allograft biopsy to detect acute rejection in patients that undergo a biopsy for unexplained renal dysfunction. The perspective of this approach is that the test could be used either in place of the biopsy or as decision guidance whether a biopsy is necessary to confirm the presence of rejection. Another perspective is that the MS test (respectively, a simplified test system derived from this method) could be used in the regular post-transplant surveillance for acute rejection, in place of the relatively insensitive procedure with periodic monitoring of the graft function by creatinine determinations.


Eligibility criteria: Inclusion Criteria:

* Adult patients with a kidney or combined kidney/pancreas transplantation
* Unexplained renal allograft dysfunction within the first year of transplantation
* Renal allograft biopsy, which is clinically indicated to verify or exclude an acute rejection

Exclusion Criteria:

* Lacking consent of the patient to participate in the study

Primary outcomes:
measure: Ability of the urine mass spectrometry test to diagnose acute renal allograft rejection, compared to the gold standard 'allograft biopsy'
timeFrame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Secondary outcomes:
measure: Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with different severity grades of the rejection
timeFrame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
measure: Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with kidney transplantation alone and with combined pancreas/kidney transplantation
timeFrame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
measure: Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with concurrent infection
timeFrame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: RTW University of Aachen
city: Berlin
country: Germany
facility: Charite Universitätsmedizin Berlin
city: Erlangen
country: Germany
facility: University of Erlangen-Nuremberg
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hannover
country: Germany
facility: Hannover Medical School
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Köln
country: Germany
facility: Kliniken der Stadt Köln gGmbH
city: München
country: Germany
facility: Ludwig-Maximilians-Universitätsklinik München
Study officials:
affiliation: Hannover Medical School
name: Wilfried Gwinner, Prof. /MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wittke S, Haubitz M, Walden M, Rohde F, Schwarz A, Mengel M, Mischak H, Haller H, Gwinner W. Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients. Am J Transplant. 2005 Oct;5(10):2479-88. doi: 10.1111/j.1600-6143.2005.01053.x.
citation: Metzger J, Chatzikyrkou C, Broecker V, Schiffer E, Jaensch L, Iphoefer A, Mengel M, Mullen W, Mischak H, Haller H, Gwinner W. Diagnosis of subclinical and clinical acute T-cell-mediated rejection in renal transplant patients by urinary proteome analysis. Proteomics Clin Appl. 2011 Jun;5(5-6):322-33. doi: 10.1002/prca.201000153. Epub 2011 Apr 29.
citation: Zapf A, Gwinner W, Karch A, Metzger J, Haller H, Koch A. Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study. BMC Nephrol. 2015 Sep 15;16:153. doi: 10.1186/s12882-015-0146-x.