5 research outputs found
Complement Is Activated During Normothermic Machine Perfusion of Porcine and Human Discarded Kidneys
Background: The gap between demand and supply of kidneys for transplantation
necessitates the use of kidneys from extended criteria donors. Transplantation of these
donor kidneys is associated with inferior results, reflected by an increased risk of delayed
graft function. Inferior results might be explained by the higher immunogenicity of
extended criteria donor kidneys. Normothermic machine perfusion (NMP) could be
used as a platform to assess the quality and function of donor kidneys. In addition, it
could be useful to evaluate and possibly alter the immunological response of donor
kidneys. In this study, we first evaluated whether complement was activated during NMP
of porcine and human discarded kidneys. Second, we examined the relationship between
complement activation and pro-inflammatory cytokines during NMP. Third, we assessed
the effect of complement activation on renal function and injury during NMP of porcine
kidneys. Lastly, we examined local complement C3d deposition in human renal biopsies
after NMP.
Methods: NMP with a blood-based perfusion was performed with both porcine and
discarded human kidneys for 4 and 6 h, respectively. Perfusate samples were taken every
hour to assess complement activation, pro-inflammatory cytokines and renal function.
Biopsies were taken to assess histological injury and complement deposition.
Results: Complement activation products C3a, C3d, and soluble C5b-9 (sC5b-9) were
found in perfusate samples taken during NMP of both porcine and human kidneys. In
addition, complement perfusate levels positively correlated with the cytokine perfusate
levels of IL-6, IL-8, and TNF during NMP of porcine kidneys. Porcine kidneys with high
sC5b-9 perfusate levels had significantly lower creatinine clearance after 4 h of NMP. In line with these findings, high complement perfusate levels were seen during NMP of
human discarded kidneys. In addition, kidneys retrieved from brain-dead donors had
significantly higher complement perfusate levels during NMP than kidneys retrieved from
donors after circulatory death.
Conclusion: Normothermic kidney machine perfusion induces complement activation in
porcine and human kidneys, which is associated with the release of pro-inflammatory
cytokines and in porcine kidneys with lower creatinine clearance. Complement inhibition
during NMP might be a promising strategy to reduce renal graft injury and improve graft
function prior to transplantation
Lipid peroxidation in multidrug-resistant Gram-negative sepsis: translating science to the septic patient?
Multidrug-resistant Gram-negative induced sepsis poses an increasing threat to the vulnerable intensive care patient. The study by Toufekoula and colleagues reports the serum and tissue concentration of malondialdehyde (MDA), the toxic end product of lipid peroxidation, during the course of experimental and human Gram-negative sepsis. The complementary results from this dual experimental and clinical approach argue for highly compartmentalized lipid peroxidation during sepsis. Establishing a correlation between MDA concentration and survival provides valuable insights into the pathophysiology of Gram-egative sepsis. Yet, further studies are needed to understand and establish MDA as a biomarker during sepsis aggravated by organ failure