Urinary Biomarkers in Paediatric Kidney Transplantation (pKTx)

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.