Determinants of acute and chronic renal allograft injury

Renal transplantation researchers have earned big successes by understanding the factors that lead to allorecognition and rejection of solid organ transplants. This knowledge has led to more effective immunosuppressive drug regimens at the cost of an increase in post-transplant infectious diseases and malignancies. Also, with the successes that are acquired with effective immunosuppression, the boundaries of renal transplantation as a therapy have been stretched over the past decades with the introduction of expanded criteria donations, prolonged cold ischemia times, increasing recipient ages and transplantation of immunologically complex cases (e.g. ABO incompatible transplantation). Altogether, this makes both acute, but especially chronic renal allograft failure a true multifactorial disease. This thesis is therefore divided in three parts: factors that define the early post-transplantation period that leads to acute kidney injury of the allograft (Part 1). This early post-transplant period has a large impact on priming of the allo-immune response. In the outpatient setting, the constant interplay between allo-immunity, physiological immune surveillance and immunosupression puts the allograft at risk for rejection, infections and immunosuppressive drug toxicity (Part 2). Ongoing, often subclinical injury to the allograft finally leads to irreversible allograft sclerosis, graft failure and the necessity for new renal replacement therapy (Part 3).
Conclusion:
This thesis described differences between various renal allograft injuries and their relative impact on graft failure. We introduced novel findings that might contribute to the way we think about the pathogenesis of ischemia-reperfusion injury, allograft rejection, viral immunity and the final common pathway of chronic allograft injury.
Besides novel finding, also the reproducibility of hypotheses that were proposed by other research groups was tested in large, independent patient cohorts. This cycle of production and reproduction promotes the science that leads to an improvement in the treatment of patients with a renal transplant.