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

Study Overview
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Brief Summary
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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.

Official Title
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Non-invasive Diagnosis of Acute Rejection in Renal Transplant Patients Using Mass Spectrometry of Urine Samples - a Multicentre Diagnostic Phase III Trial

Conditions
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Rejection of Renal Transplant

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with different severity grades of the rejection | Sensitivity/specificity measures for the urine test will be determined in subgroups of patients with different severity of the rejection. Severity grading is based on the pathomorphological classification of the rejection (according to the BANFF classification) and on the functional impairment of the allograft at the time of rejection diagnosis. | 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 | Sensitivity/specificity measures for the urine test will be determined in subgroups of patients who have a kidney transplant or a combined pancreas/kidney transplant. | 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 | Sensitivity/specificity measures for the urine test will be determined in subgroups of patients who have concurrent infections at the time of the biopsy and urine sampling such as cytomegaly virus, polyoma virus, and urinary tract infection. The analysis intends to identify potential interference of these conditions with the urine mass spectrometry test. | Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplantation, acute rejection, diagnosis, urine analysis, urinary peptides, mass spectrometry, allograft biopsy, pathology, diagnostic study