Sepsis has been well recognized as a systemic inflammatory response (SIRS) to an active infectious process in the host and it is a common cause of AKI ("Sessler CN-2002" [1]). Tubular apoptosis and fibrosis play a key role in AKI ("Lerolle N-2010") [2].
The use of sorbents, typically resins, in extracorporeal therapy in particular CPFA, has revealed a remarkable effectiveness for blood detoxification and for improving the survival of septic subjects with AKI ("Rimellé T-2011"). [3] (full text).
The aim of our study was to investigate the efficacy of CPFA in preventing renal damage in a swine model of sepsis-induced AKI.
After 3 h from LPS infusion, 8 pigs were treated with CPFA for 6 h; 8 control pigs receive no treatment. Renal biopsies were performed before (T0) and 9 hours (T9) after LPS infusion.
In septic pigs (T9 LPS), Masson's trichrome staining revealed an early fibrosis characterized by extensive collagen deposition at the interstitial level (51.54±8.28, vs T0:11.96±5.33 p=0.04) and diffuse glomerular thrombi at T9 (B) compared to T0 (A) (Figure 1, A-C). Moreover an interstitial increase of the myofibroblast marker α-SMA was observed in septic renal tissue (E) respect to T0 (D) by immunofluorescence analysis (7.58±0.49 fold change,p=0.001) (Figure 1, D-F). Immunohistochemical analysis for Caspase-3 showed an intense apoptosis (B) of tubular cells after LPS infusion (T9:40.44±9.04 vs T0:11.07±3.96 p=0.0002) (Figure 2, A-C).
Interestingly CPFA treated pigs (T9 LPS CPFA) showed a significant reduction in collagen deposits (25.29±8.9 p=0.04) and glomerular thrombi (B) compared to untreated animals (A) (Figure 3, A-C). Overall, α-SMA expression (Figure 3, D-F) (2.43±0.31 fold change, p=0.001), as well as tubular apoptosis (Figure 4, A-C) (20.96±2.68 p=0.004) were strongly reduced by CPFA treatment.
Our data demonstrated the occurrence of tubular apoptosis and renal fibrosis in sepsis-induced AKI. CPFA treatment might be pivotal to counteract the detrimental effects of LPS on renal tissue.
[1] Sessler CN, Shepherd W New concepts in sepsis. Current opinion in critical care 2002 Oct;8(5):465-72
[2] Lerolle N, Nochy D, Guérot E et al. Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration. Intensive care medicine 2010 Mar;36(3):471-8
[3] Rimmelé T, Kellum JA Clinical review: blood purification for sepsis. Critical care (London, England) 2011;15(1):205 (full text)
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