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NCT Number: NCT05208788

Urinary Biomarkers in Paediatric Kidney Transplantation (pKTx)

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.

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Key information

Conditions

Renal Transplantation Chronic Disease Chronic Kidney Insufficiency Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Healthy Controls Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

0 year–17 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University Children's Hospital Tuebingen

Tübingen, 72076, Germany

About this study

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.

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

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).

Treatment and study plan

Biomarker test

Diagnostic Test

collection of 500µl to 1 ml of a spot urine sample

Primary outcomes

  1. Change of serum creatinine level [mg/dl]

    Time frame: from Baseline up to 18 months

    Standard surveillance parameter of kidney function / renal allograft

  2. Change of serum urea level [mg/dl]

    Time frame: from Baseline up to 18 months

    Standard surveillance parameter of kidney function / renal allograft

  3. Change of serum Cystatin C level [mg/l]

    Time frame: from Baseline up to 18 months

    Standard surveillance parameter of kidney function / renal allograft

  4. Measurement of urine creatinine level [g/l]

    Time frame: from Baseline up to 18 months

    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).

  5. Change of urine alpha-1-Microglobulin (A1M)

    Time frame: from Baseline up to 18 months

    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.

  6. Change of urine Aquaporin 2 (AQP2) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  7. Change of urine Caldesmon [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  8. Change of urine Clusterin [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  9. Change of urine Cystatin C [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  10. Change of urine Interleukin 9 (IL-9) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  11. Change of urine Kidney injury molecule 1 (Kim-1) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  12. Change of urine Nephrin [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  13. Change of urine Neutrophil gelatinase-associated lipocalin (NGAL) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  14. Change of urine Osteopontin (OPN) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  15. Change of urine P-selectin (SELP) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  16. Change of urine Podocin [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  17. Change of urine Retinol-binding protein 4 (RBP4) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  18. Change of urine Smoothelin [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  19. Change of urine Synaptopodin [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  20. Change of urine tumour necrosis factor alpha (TNF-α) [ng/ml]

    Time frame: from Baseline up to 18 months

    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.

  21. Change of urine vascular cell adhesion molecule-1 (VCAM-1)

    Time frame: from Baseline up to 18 months

    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.

Sponsors and collaborators

Lead sponsor

University Hospital Tuebingen

Other

Collaborators

  • Cooperative European Paediatric Renal Transplant Initiative (CERTAIN)
  • Natural and Medical Sciences Institute (NMI)

Registry information

Official study title

Estimation of Kidney Function Through a Combination of Renal Urinary Biomarkers in Paediatric Renal Transplant Patients - A Multi-centre Prospective Observational Study

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Jan 26, 2022
Registry last updated
Nov 29, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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