In chapters 2, 3 and 4, novel biomarkers IGFPB7, TIMP-2 and long noncoding RNAs were studied in order to find new diagnostic possibilities for early recognition and diagnosis of injury in native... Show moreIn chapters 2, 3 and 4, novel biomarkers IGFPB7, TIMP-2 and long noncoding RNAs were studied in order to find new diagnostic possibilities for early recognition and diagnosis of injury in native and transplanted kidneys. In chapter 2, diabetic nephropathy was found to be associated with higher levels of circulating TIMP-2, which did not normalize after simultaneous pancreas-kidney transplantation. In chapter 3, we found that four circulating long noncoding RNAs associated with diabetic nephropathy and did normalize after simultaneous pancreas-kidney transplantation. In chapter 4, acute rejection in kidney transplant recipients resulted in higher circulating LNC-EPHA6 levels. In chapter 5, clinical parameters and single antigen bead assay for measurement of donor specific antibodies were evaluated in the context of antibody-mediated rejection. Female recipients who received a kidney transplant from their spouse were especially at risk for acute antibody-mediated rejection and a single antigen bead assay is more sensitive to detect antibodies in this group than the standard diagnostic strategy. In chapter 6, mesenchymal stromal cell therapy is studied in a randomized controlled trial to evaluate the potential for prevention of acute rejection and fibrosis in transplanted kidneys. MSC therapy resulted in similar fibrosis scores and rejection rates. Show less
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... Show moreIn 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. Show less
Kidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of... Show moreKidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of DGF, response to steroid resistant rejection and long-term graft outcome remain difficult when using merely clinical parameters. Numerous studies have reported on the predictive value of molecular markers for AR and worse graft outcome. However, the heterogeneity of AR and the variation among transplant centers leads to controversial results and preclude a more general clinical application. In the first part of this thesis, we aimed to investigate the molecular markers of steroid resistance and long-term graft survival on the basis of acute rejection biopsies. In the second part, we focused on genetic variants associated with acute rejection in kidney transplantation. In the final part we described the possible immune regulatory effect of S100 calcium binding proteins. Show less
