Background: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine. Methods: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 infection admitted to the ICU. AP or a placebo was administered for four days following admission to the ICU. The primary outcome was the duration of mechanical ventilation. Mortality in 28 days, acute kidney injury, need for reintubation, safety, and inflammatory markers relevant to the described high cytokine release associated with SARS-CoV-2 infection were the secondary outcomes. Results: Between December 2020 and March 2022, 97 patients (of the intended 132) were included, of which 51 were randomised to AP. The trial was terminated prematurely based on meeting the threshold for futility. Compared to the placebo, AP did not affect the duration of mechanical ventilation (9.0 days vs. 9.3 days, p = 1.0). No safety issues were observed. After 28 days, mortality was 9 (18%) in the AP group versus 6 (13%) in the placebo group (p = 0.531). Additionally, no statistically significant differences between the AP and the placebo were observed for the other secondary outcomes. Conclusions: Alkaline phosphatase (AP) therapy in COVID-19 ICU patients showed no significant benefits in this trial.

Background.: Kidney preservation techniques, such as hypothermic machine perfusion (HMP), improve graft outcomes in deceased-donor kidney transplantation by pausing graft metabolism and ameliorated ischemia–reperfusion injury (IRI) but do not completely eliminate injury. Alkaline phosphatase (ALP) has been postulated to reduce IRI-induced kidney injury through the conversion of extracellular adenosine triphosphate into adenosine. This study aimed to evaluate whether ALP offers protection during deceased-donor kidney storage. Methods.: Sixteen abattoir porcine kidneys (8 ALP and 8 with placebo) were procured after euthanization and exposed to 30 min of warm ischemia followed by 24 h of HMP or static cold storage (SCS). Reperfusion was partly simulated by 240 min of normothermic machine perfusion (NMP). Throughout NMP, we obtained functional, biochemical, and histological parameters. Results.: Significantly lower urine production accompanied by lower perfusate pCO ₂ and higher pH were observed in the ALP group throughout NMP. At the end of NMP, intracellular ATP reserves and oxygen consumption were significantly higher in the ALP-treated group. Metabolomics analysis with principal component analysis demonstrated significant differences between the ALP and placebo groups in glycolysis and mitochondrial metabolites, along with a significantly attenuated rise in perfusate lactate dehydrogenase levels. Conclusions.: ALP supplementation during HMP was associated with lower urine production and energetic stress, with a shift toward less metabolic dysfunction and graft injury by the end of NMP. Our findings suggest an improvement in the early metabolic incompetency that characterizes delayed graft function in humans. Further research should elucidate whether these findings result in enhancement of graft functionality after transplantation.