Diagnosis of Acute Rejection in Renal Transplant Patients by Urine Mass Spectrometry

NCT01315067 | Completed DMC

• 1 other identifier: MS-GW4/6-1
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 8

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.

Conditions

Rejection of Renal Transplant

Keywords

kidney transplantation; acute rejection; diagnosis; urine analysis; urinary peptides; mass spectrometry; allograft biopsy; pathology; diagnostic study

Outcome Measures

Primary Outcomes (1)

• Ability of the urine mass spectrometry test to diagnose acute renal allograft rejection, compared to the gold standard 'allograft biopsy'

  In patients with unexplained renal allograft dysfunction who get an allograft biopsy to clarify if an acute rejection is present, a simultaneous urine sample will be taken. The peptide pattern of this urine sample is analyzed by mass spectrometry and a diagnosis is made (rejection present/not present) based on a pre-defined peptide pattern which was established to detect acute allograft rejection. In the primary outcome analysis, the sensitivity and specificity of the rejection diagnosis by the urine test is compared to the diagnosis made by the allograft biopsy.

  Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)

Secondary Outcomes (3)

• Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with different severity grades of the rejection

  Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)

• 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

  Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)

• Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with concurrent infection

  Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• Lacking consent of the patient to participate in the study

Sponsors & Collaborators

• Hannover Medical School: lead

Study Sites (8)

RTW University of Aachen

Aachen, 52074, Germany

Location

Charite Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Kliniken der Stadt Köln gGmbH

Cologne, 51109, Germany

Location

University of Erlangen-Nuremberg

Erlangen, 90154, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Ludwig-Maximilians-Universitätsklinik München

München, 81377, Germany

Location

Related Publications (3)

• 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.

  PMID: 16162198 BACKGROUND

• 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.

  PMID: 21538920 BACKGROUND

• 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.

  PMID: 26374548 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine samples, kidney allograft biopsies

MeSH Terms

Conditions

Disease

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wilfried Gwinner, Prof. /MD

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: March 14, 2011
• First Posted: March 15, 2011
• Study Start: October 1, 2011
• Primary Completion: March 1, 2017
• Study Completion: June 15, 2017
• Last Updated: August 10, 2017

Record last verified: 2017-08

Locations

DE (8)