Molecular signatures underlying kidney transplantation: towards a tailored treatment

Due to the shortage of organ donors, kidney patients have to wait longer and longer for a donor kidney. Therefore, suboptimal donor kidneys are increasingly used to expand the donor pool. These donor kidneys are more damaged because they are obtained from an older donor, for example, or because they have been without oxygen for a more extended period of time. As a result, the risk of complications is much higher. In addition, many of the underlying protein processes associated with damage are still unknown. The interplay between proteins is essential for the proper functioning of the human body and thus the kidneys. Proteomics techniques are used to study all proteins in a cell or organ to identify which proteins are dysregulated during damage. Normothermic machine perfusion is a technique to fully activate the kidney its metabolism and function outside the body at 37 degrees Celsius. This also allows testing of the organ's functionality and administration of medication for damage repair. This thesis aimed to map out the dysregulated protein profiles during kidney transplantation using proteomics techniques, and translate these results into tailored treatments during machine perfusion. With this research, we have identified new underlying protein processes and shown that machine perfusion can be used as a platform to deliver drugs to a kidney outside the body. In the future, this strategy could be used to improve the quality of donor organs.