PhD defence J.G.H.P. (Jeroen) Verhoeven

Summary:

Solid organ transplantation is the treatment of choice for patients with end-stage heart and kidney disease. Allograft rejection (AR) is an important complication affecting 10-20% of
kidney transplantations and around 25% of heart transplantations within the fi rst year after transplantation (1-3). AR may cause irreversible allograft injury limiting the survival of the allograft and the recipient (2). Therefore, early diagnosis and appropriate treatment is necessary. Shortcomings of the currently used diagnostic methods to diagnose AR are the following: 1) the gold standard to diagnose AR, an allograft biopsy, is an invasive and costly procedure which is subject to interpretation and sampling error (4, 5); 2) the conventional biomarkers used (e.g. serum creatinine concentrations and urinary protein concentrations) are insensitive and non-specifi c for AR as these biomarkers only increase (indicating allograft injury) when a substantial amount of allograft tissue has been damaged (6). For these reasons, novel and minimally-invasive biomarkers are needed which are ideally sensitive and specifi c for AR and may ultimately reduce the number of allograft biopsies (7, 8). The overall aim of the studies performed in this thesis was to examine the diagnostic performance of three minimally-invasive biomarkers for AR: donor-derived cell-free DNA (ddcfDNA), circulating cell-free nucleosomes (CCFN), and circulating endothelial cells (cECs).