Urinary Biomarkers in Paediatric Kidney Transplantation (pKTx)
Condition: Renal Transplantation; Chronic Kidney Insufficiency; Healthy Controls
MeSH terms: Renal Insufficiency; Renal Insufficiency, Chronic
Study type: Observational

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.
    

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.

      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.
    

Intervention name(s): Biomarker test
Intervention type(s): Diagnostic Test
Intervention description(s): collection of 500µl to 1 ml of a spot urine sample
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        children < 18 years
      
Biospecimen description: 
      Spot urine samples
    
Keywords: renal transplantation; biomarkers