Urinary Biomarkers in Paediatric Kidney Transplantation (pKTx)

NCT05208788 | Completed

• 1 other identifier: pKTx/318/2021BO1
• Study Type: observational
• Target: 186
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Transplantation; Chronic Kidney Insufficiency; Healthy Controls

Keywords

renal transplantation; biomarkers

Outcome Measures

Primary Outcomes (21)

• Change of serum creatinine level [mg/dl]

  Standard surveillance parameter of kidney function / renal allograft

  from Baseline up to 18 months

• Change of serum urea level [mg/dl]

  Standard surveillance parameter of kidney function / renal allograft

  from Baseline up to 18 months

• Change of serum Cystatin C level [mg/l]

  Standard surveillance parameter of kidney function / renal allograft

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  from Baseline up to 18 months

Study Arms (4)

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

Biomarker test DIAGNOSTIC_TEST

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

Healthy controls; Patients with Chronic Kidney Disease Stage IV and V (CKD IV-V) - group 3; Renal transplant patients - group 1; renal transplant patients - group 2

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

children \< 18 years

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• Natural and Medical Sciences Institute (NMI): collaborator
• Cooperative European Paediatric Renal Transplant Initiative (CERTAIN): collaborator

Study Sites (1)

University Children's Hospital Tuebingen

Tübingen, 72076, Germany

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Spot urine samples

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

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

Study Officials

• Marcus Weitz, PD Dr. med.

  University Children's Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: January 26, 2022
• Study Start: June 1, 2021
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)