Early monitoring strategies in kidney transplant recipients

Abstract

In this thesis, we focus on recipients of donation after circulatory death (DCD) kidneys in the first months after transplantation. DCD kidney transplant recipients have an increased risk of early complications post transplantation such as acute rejection and delayed graft function (DGF). A sensitive and specific biomarker to monitor the occurrence of an acute rejection episode or (the resolution of) DGF is unfortunately not available to date. For a definite diagnosis, a kidney allograft biopsy remains the so-called ‘golden standard’. A percutaneous kidney biopsy is, however, an invasive procedure with a risk of bleeding complications. Guidance in daily clinical practice by a simple but reliable marker is needed, and can help to monitor regular resolution of DGF and/or identify intercurrent problems such as acute rejection episodes. In the current thesis we investigated risk factors of acute rejection and DGF. In addition, the most promising biomarkers of kidney injury according to current literature (i.e. KIM-1, NGAL, TIMP-2, IGFBP7) were investigated in the prediction of DGF and acute rejection. Furthermore, we used an alternative approach in the search for biomarkers by analyzing smaller molecules with Nuclear Magnetic Resonance (NMR) spectroscopy.

We still have not found the ‘perfect’ biomarker to monitor acute rejection DGF after kidney transplantation, however of all biomarkers investigated TIMP-2 showed the greatest potential. Using the approach of metabolomics, we were able to identify new biomarkers. Further studies are needed to confirm and validate these results and evaluate their usefulness in daily clinical practice.