CompletedNCT05208788Updated Nov 29, 2023

Urinary Biomarkers in Paediatric Kidney Transplantation (pKTx)

An observational study in Renal Transplantation, Chronic Kidney Insufficiency and Healthy Controls, sponsored by University Hospital Tuebingen. Completed at 1 site in Germany. Open to participants aged 0 Years to 17 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-11-29.

Sponsored by University Hospital Tuebingen · Observational

Study type: Observational
Model: Case-control
Time perspective: Prospective
Enrollment: 186
Ages: 0 Years to 17 Years
Sex: All

Study summary

This study aims to test and validate the panel of study urinary biomarker to assess whether (1) reference values differ between paediatric renal transplant patients, patients with chronic kidney disease stage IV and V (CKD IV-V) and children without any disease, (2) characteristic changes in concentration profile may be observed after event-specific injury, (3) differences between paediatric renal transplant patients with AR and other causes of AKI can be detected, and (4) stratification of renal transplant patients to different histological types of AR is possible.

Read the detailed description

Despite advances in kidney transplantation, acute rejection (AR) is one of the primary risk factors for allograft kidney injury and function deterioration, and may have a significant impact on long-term graft survival, particularly in paediatric renal transplant patients. Against the background of the limited availability of kidney donor organs, the early recognition of AR is of particular interest to improve long-term allograft survival. Renal allograft biopsy remains the current gold standard for the diagnosis of kidney transplant rejection. However, it is an invasive procedure associated with the risk of bleeding, infection of the renal allograft, arterio-venous fistula, introducing sampling error, and a large inter-observer variation. Therefore, urinary biomarkers from minimally invasive compartments would be helpful for the early detection of clinical rejection before graft functional decline occurs. The current standard monitoring of the renal transplant function includes measurements of serum-creatinine (SCr) levels, estimatedglomerular filtration rate (eGFR), and proteinuria. These markers exhibit a lack of sensitivity and specificity and are late indicators for molecular and cellular events following AR. Furthermore, conditions other than AR (viral and bacterial infection, calcineurin nephrotoxicity, acute ischemic injury) resemble similar morphological features within the renal allograft challenging detection and differentiation of the underlying process. Early treatment of AR could lead to diminished histological injury and improved functional outcome. An intensified immunosuppression management represents the main strategy to counteract the uncontrolled attack of the recipient´s immune system against the renal allograft.

Not surprisingly, many attempts have been made to develop new biomarkers to improve the precision and accuracy in detecting AR for optimizing immunosuppression management. Because allograft reactive cells can gain access to the urinary space, urine represents an appropriate biospecimen to investigate allograft injury. The study urinary biomarkers have been partially discovered and characterized in the past for detection of acute kidney injury (AKI), rarely in renal transplant patients.

Conditions studied

Renal Transplantation
Chronic Kidney Insufficiency
Healthy Controls

Browse trials for

Renal Insufficiency, Chronic 3,224

Keywords

renal transplantation
biomarkers

In context

Renal Insufficiency, Chronic

3,224 studies on the registry are indexed under Renal Insufficiency, Chronic; 706 are open to participants now.

This study's enrollment of 186 is close to the median of 200 across 889 observational studies indexed under Renal Insufficiency, Chronic.

Browse Renal Insufficiency, Chronic studies →

Lead sponsor

University Hospital Tuebingen is the lead sponsor of 490 studies on the registry; 108 are open to participants now.

Browse University Hospital Tuebingen studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 0 Years to 17 Years
Sexes eligible: All
Accepts healthy volunteers: Yes
Sampling method: Probability sample

Study population

children \< 18 years

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

i) Group 1 (patients \< 18 years of age)- obtaining reference values without any of the pre-defined events

renal transplant patients with stable renal function parameters (mean SCr (or cystatin C) or mean eGFR based on creatinine and / or cystatin C defined as changes ≤ ±15 % for at least three consecutive ambulatory controls).
patients with CKD IV-V (and maintained urine output, without renal replacement therapy and without pre-defined events).
healthy controls.

Study patients from group 1 may be assigned to the group 2 in the following conditions:

ii) Group 2 (patients \< 18 years of age)- obtaining biomarker-specific characteristic in the presence of any of the pre-defined events

renal transplant recipients with living or deceased kidney transplantation.
patients with CKD IV-V (and maintained urine output without renal replacement therapy).
healthy controls.

Exclusion criteria

Exclusion Criteria:

i) Healthy controls

any comorbidity / medication which may have an impact on urinary biomarker profile (e.g. primary kidney or liver disease, metabolic disease, vasculitis or other immunological disease other than the pre-defined events).
for group 1: presence of any of the pre-defined event. ii) CKD IV-V
any comorbidity / medication which may have an impact on urinary biomarker profile (e.g. liver disease, metabolic disease, vasculitis or other immunological disease other than the pre-defined events).
for group 1: presence of any of the pre-defined event. iii) Renal transplant patients for group 1: presence of any of the pre-defined event.
Primary non-function of the renal transplant organ.
Blood group (AB0) incompatible.
Detection of donor specific antibody (DSA) positive (panel-reactive antibodies) at time of enrolment.
any comorbidity / medication which may have an impact on urinary biomarker profile (e.g. liver disease, metabolic disease, vasculitis or other immunological disease) other than the pre-defined events.
Presence of other transplanted organs or co-transplanted organs.
Intention to not use a standard maintenance immunosuppression regimen consisting of calcineurin inhibitor (CNI), antimetabolite (mycophenolate or azathioprine), inhibitor of mechanistic target of rapamycin (mTOR) (Sirolimus / Everolimus) with/without corticosteroids.
Any condition that, in the opinion of the investigator, would pose risk to the subject's safe participation, or interfere with their ability to comply with the study requirements, or may impact the quality of the interpretation of the data (e.g. detection of malignancy).
Failure to collect urine samples or incomplete additional CERTAIN dataset (for collecting information about pre-defined events).

Study design

Observational model: Case-control
Time perspective: Prospective
Enrollment: 186 participants (actual)
Patient registry: No
Biospecimen retention: Samples without dna

Groups and cohorts

Renal transplant patients - group 1
Renal transplant patients with stable renal function parameters (mean SCr (or cystatin C) or mean eGFR based on creatinine and / or cystatin C defined as changes ≤ ±15 % for at least three consecutive ambulatory controls).
Diagnostic Test: Biomarker test
renal transplant patients - group 2
Renal transplant recipients with stable renal function at inclusion, facing a pre-defined event during the course of the study. Pre-defined events are Acute Rejection (AR), viral transplant-associated infection (e.g. BKV), bacterial infection (febrile urinary tract infection (fUTI)), calcineurin-inhibitor (CNI) toxicity, and acute tubular necrosis (ATN).
Diagnostic Test: Biomarker test
Patients with Chronic Kidney Disease Stage IV and V (CKD IV-V) - group 3
Patients with CKD IV-V (and maintained urine output, without renal replacement therapy and without pre-defined events).
Diagnostic Test: Biomarker test
Healthy controls
Healthy children serve as control group
Diagnostic Test: Biomarker test

Interventions

Diagnostic testBiomarker test
collection of 500µl to 1 ml of a spot urine sample

What researchers measure

Primary outcomes

Change of serum creatinine level [mg/dl]
Standard surveillance parameter of kidney function / renal allograft
Time frame: from Baseline up to 18 months
Change of serum urea level [mg/dl]
Standard surveillance parameter of kidney function / renal allograft
Time frame: from Baseline up to 18 months
Change of serum Cystatin C level [mg/l]
Standard surveillance parameter of kidney function / renal allograft
Time frame: from Baseline up to 18 months
Measurement of urine creatinine level [g/l]
Standard surveillance parameter of renal function / renal allograft. All urinary study biomarkers (see below) will be correlated to urine creatinine level \[ng/mg Creatinine\] and compared with standard surveillance parameters of kidney function / renal allograft (see Outcome 1-3).
Time frame: from Baseline up to 18 months
Change of urine alpha-1-Microglobulin (A1M)
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Aquaporin 2 (AQP2) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Caldesmon [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Clusterin [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Cystatin C [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Interleukin 9 (IL-9) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Kidney injury molecule 1 (Kim-1) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Nephrin [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Neutrophil gelatinase-associated lipocalin (NGAL) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Osteopontin (OPN) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine P-selectin (SELP) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Podocin [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Retinol-binding protein 4 (RBP4) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Smoothelin [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine Synaptopodin [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine tumour necrosis factor alpha (TNF-α) [ng/ml]
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months
Change of urine vascular cell adhesion molecule-1 (VCAM-1)
Urinary study biomarker. The performance (sensitivity, specificity, positive predictive value and negative predictive value) for detection of kidney / graft deterioration will be calculated using receiver operator characteristics (ROC) curves.
Time frame: from Baseline up to 18 months

Study locations

1 site

University Children's Hospital Tuebingen
Tübingen, 72076, Germany

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jun 2021 to primary completion in Feb 2023, 20 months.

Of 288 non-industry observational studies under Renal Insufficiency, Chronic, half reached primary completion within 48 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 191. This study's 20 months is below that.

Counting every sponsor, half of 345 studies reached it within 40 months; a quarter within 20 and three quarters within 128.

How these figures are worked out, and which studies are left out of them.

Registered: Jul 12, 2021
First posted: Jan 26, 2022
StartActual: Jun 1, 2021
Primary completionActual: Feb 1, 2023
CompletionActual: Feb 1, 2023
Last update: Nov 29, 2023

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Nov 29, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05208788
Lead sponsor: University Hospital Tuebingen
Collaborators: Natural and Medical Sciences Institute (NMI), Cooperative European Paediatric Renal Transplant Initiative (CERTAIN)
Responsible party: Sponsor
First posted: Jan 26, 2022
Start date: Jun 1, 2021
Primary completion: Feb 1, 2023
Completion: Feb 1, 2023
Last update: Nov 29, 2023

Study contacts

Marcus Weitz, PD Dr. med.

principal investigator · University Children's Hospital Tuebingen

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Nov 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Renal Insufficiency, Chronic →

Other studies from this sponsor

University Hospital Tuebingen →

Start the discussion