Janssen&Janssen schreef op 22 december 2021 13:59:
[...]
Belangrijkste stuk wat me nu opvalt
DGF results from acute kidney injury (AKI) suffered dur- ing ischemia-reperfusion injury (IRI) in transplantation. Increased inflammatory response, complement activation, and cytokine release are all implicated in the pathogenesis of DGF.18-21 The complement system, consisting of classi- cal pathways (CPs), mannose-binding lectin (MBL), and alternative pathways (APs), is an essential component of the innate immune system.18-20 Complement-mediated injury starts in the donor with increased mRNA expres- sion of complement components and upregulation of renal tubular anaphylatoxin receptors C3aR and C5aR.22,23 Although the liver produces the majority of complement proteins, up to 10%–16% of systemically circulating C3, a precursor of C5 convertase, is produced by renal proximal tubular cells.19,22,24-30 These factors foster local comple- ment deposition, leukocyte migration and infiltration, and oxidative damage, exacerbating injury at reperfusion and increasing the risk of DGF and rejection.19,25,31-42
C1esteraseinhibitor(C1INH)isaserineproteaseinhib- itor that blocks components of the complement, contact, fibrinolytic, and coagulation systems.43 Currently approved by Food and Drug Administration for use in hereditary angioedema, C1INH products have garnered interest in the transplant community as a mitigator of IRI because of its anti-inflammatory properties.43 In humans, C1INH blocks the classical complement and MBL pathways by inactiva- tion of C1s, C1r, and MASP2.43 This effect is potentiated by heparin, commonly used in organ procurement and transplantation, increasing the activity of C1INH up to 11-fold.44-46