Rescue alkaline phosphatase in ischemic kidney damage Target then treat

This thesis centers exploring kidney transplantation and acute kidney injury (AKI), with a particular focus on the therapeutic potential of alkaline phosphatase (AP) to mitigate ischemia-reperfusion injury (IRI) by modulating the host and injury response. To better understand AKI following transplantation, we investigated early graft dysfunction across donor types using data from the Dutch National Transplant Registry. The analysis compared delayed graft function (DGF), slow graft function (SGF), and immediate graft function (IGF) in kidneys from donation after brain death (DBD) and donation after circulatory death (DCD). While long-term graft survival was similar, early dysfunction patterns and clinical implications varied, underscoring the need for tailored post-transplant care.
In two biomarker studies, we examined AKI in critically ill patients with COVID-19 and sepsis. Findings suggest that these are distinct entities, with urinary CCL14 serving as a potential marker of severe host-response dysregulation closely tied to AKI development. We also explored AP’s therapeutic potential in a narrative review, particularly for sepsis-associated AKI, where preclinical studies showed promise, though clinical efficacy remains unproven.
To explore clinical translation, we administered AP in a porcine model of donor kidney storage to assess its capacity to preserve cellular metabolism and reduce injury. Finally, in a pilot study, we administered bovine-derived AP (bRESCAP) to living donor kidney transplant recipients, evaluating its safety, feasibility, and impact on graft function one year post-transplant, using measured glomerular filtration rate (mGFR) and kidney injury biomarkers.