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Published on: February 15, 2022
Polymyxin B hemoperfusion prevents acute kidney injury in sepsis model
Chieko Mitaka1, Takahiro Masuda2, Koji Kido3
1Department of Anesthesiology, Juntendo University Hospital, Tokyo, Japan; Department of Anesthesiology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Background:
Direct hemoperfusion with a polymyxin B-immobilized column (PMX-DHP) adsorbs endotoxin and has been used for the treatment of septic shock. Yet, the mechanisms by which PMX-DHP acts on acute kidney injury are only partially understood.
Materials And Methods:
Rats were anesthetized, tracheostomized, and placed on mechanical ventilation. The animals were randomized to three groups: a cecal ligation and puncture (CLP) + dummy-DHP group (n = 10), a CLP + PMX-DHP group (n = 10), and a sham group (n = 4). Four hours after CLP, a dummy-DHP or PMX-DHP was performed for 1 h. The heart rate, mean arterial pressure, arterial blood gases, and plasma concentrations of creatinine, lactate, potassium, interleukin (IL)-6, and IL-10 were measured at 0 h and 8 h. Eight hours after CLP, the kidney was harvested, and histopathologic examination was performed. The expressions of cleaved poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-κB p65 were examined by immunohistochemistry. A terminal deoxynucleotide transferase dUTP nick-end labeling assay was performed to detect apoptotic nuclei in kidney sections.
Results:
PMX-DHP maintained hemodynamics and the acid-base balance and significantly (P < 0.05) decreased the plasma concentrations of lactate, creatinine, potassium, IL-6, and IL-10 compared with dummy-DHP. PMX-DHP significantly (P < 0.001) attenuated the expressions of cleaved PARP and NF-κB p65 in renal tubular cells and renal tubular cell apoptosis compared with dummy-DHP.
Conclusions:
These findings suggest that PMX-DHP may protect against acute kidney injury not only by inhibiting the NF-κB signaling pathway but also by preventing renal tubular cell apoptosis.
Insights
Polymyxin B-immobilized column direct hemoperfusion (PMX-DHP) improved hemodynamics and reduced inflammatory markers in septic shock. PMX-DHP also protected against acute kidney injury by inhibiting NF-κB signaling and preventing tubular cell apoptosis.
Area of Science:
- Nephrology
- Critical Care Medicine
- Sepsis Research
Background:
- Direct hemoperfusion with polymyxin B-immobilized columns (PMX-DHP) is used for septic shock, adsorbing endotoxins.
- The precise mechanisms by which PMX-DHP mitigates acute kidney injury (AKI) remain incompletely understood.
Purpose of the Study:
- To investigate the protective effects of PMX-DHP on kidney injury in a rat model of septic shock.
- To elucidate the molecular pathways involved in PMX-DHP's renoprotective actions.
Main Methods:
- A cecal ligation and puncture (CLP) rat model was used, with groups receiving either PMX-DHP, a dummy column, or sham procedure.
- Hemodynamic parameters, blood gases, and plasma biomarkers (creatinine, lactate, IL-6, IL-10) were measured.
- Renal tissue was analyzed for cleaved poly (ADP-ribose) polymerase (PARP), nuclear factor-kappa B (NF-κB) p65 expression, and apoptosis.
Main Results:
- PMX-DHP stabilized hemodynamics and acid-base balance, significantly reducing lactate, creatinine, potassium, IL-6, and IL-10 levels compared to the dummy group.
- PMX-DHP markedly attenuated the expression of cleaved PARP and NF-κB p65 in renal tubular cells.
- PMX-DHP significantly reduced renal tubular cell apoptosis.
Conclusions:
- PMX-DHP demonstrates renoprotective effects in septic shock, likely through inhibiting the NF-κB signaling pathway.
- Preventing renal tubular cell apoptosis is a key mechanism by which PMX-DHP mitigates acute kidney injury.
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