Role of OPG/RANKL/RANK/TLR4 signaling pathway in sepsis-associated acute kidney injury.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) has high mortality rates. The osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK)/Toll-like receptor 4 (TLR4) pathway and its potential role in SA-AKI pathogenesis remain to be fully understood. Herein, we addressed this issue using mouse models. METHODS: An SA-AKI mouse model was established using the cecal ligation and puncture method (CLP). Mice were grouped into sham, CLP model, CLP + recombinant RANKL, and CLP + anti-RANKL groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured to assess kidney function. ELISA was used to detect serum IL-1ß, TNF-α, and IL-6 levels. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of OPG, RANKL, RANK, and TLR4 in kidney tissues. HE staining was performed to evaluate the pathological changes. RESULTS: The CLP model group showed higher levels of Scr and BUN, indicating impaired kidney function in SA-AKI, compared to the sham group. Treatment with recombinant RANKL in the CLP + recombinant RANKL group reduced Scr and BUN levels, while anti-RANKL treatment in the CLP + anti-RANKL group elevated their levels. Moreover, the CLP model group had significantly increased IL-1ß, TNF-α, and IL-6 than the sham group, indicating elevated inflammation in SA-AKI. The CLP + recombinant RANKL group demonstrated decreased cytokine levels, whereas the CLP + anti-RANKL group showed an increase. Additionally, the histopathological evaluation revealed distinct kidney tissue damage in the CLP model group. Recombinant RANKL treatment reduced this damage, while anti-RANKL treatment exacerbated it. Mechanically, the mRNA and protein expression of RANKL were significantly decreased, while those of OPG, RANK, and TLR4 were significantly increased in the CLP model group and the CLP + anti-RANKL group. Interestingly, treatment with recombinant RANKL reversed these changes, as evidenced by significantly increased RANKL but decreased OPG, RANK, and TLR4. CONCLUSION: The OPG/RANKL/RANK/TLR4 pathway is involved in SA-AKI pathogenesis. Recombinant RANKL treatment attenuates the inflammatory response and kidney tissue damage in SA-AKI, possibly via regulating this pathway. This pathway shows promise as a therapeutic target for SA-AKI.

A Retrospective Study of Hemodynamic Changes in Patients After Off-Pump Coronary Artery Bypass Graft Surgery Using Impedance Cardiography.

BACKGROUND This study aimed to investigate the role of impedance cardiography (ICG) to evaluate hemodynamic changes in patients after off-pump coronary artery bypass graft (OPCABG) surgery. MATERIAL AND METHODS One-hundred and sixty patients who had undergone OPCAGB were enrolled and assessed using New York Heart Association NYHA functional class (II, II, and IV). ICG was used to measure the stroke volume (SV), stroke volume index (SI), cardiac output per minute (CO/min), cardiac index (CI), end-diastolic volume (EDV), pre-ejection period (PEP), left ventricular ejection time (LVET), systolic time ratio (STR), left ventricular ejection fraction (LVEF), acceleration index (ACI), systemic vascular resistance (SVR), and thoracic fluid content (TFC). The ICG parameters were correlated with brain natriuretic peptide (BNP) and echocardiography parameters using multivariate regression analysis. RESULTS The levels of CO, ACI, TFC, SVR, and BNP compared with ICG showed differences between NYHA functional class, with CO showing a significant difference (p<0.05). There were no significant differences between SV, SI, EDV, and LVEF before and after OPCAGB. Using ICG, the parameters of CI, LVEF, EDV, and TFC showed no significant correlation with BNP. SV, SI, CO, ACI, and LVET, which were negatively correlated with BNP. SVR, PEP, and STR were positively correlated with BNP (P<0.05). CONCLUSIONS In patients who had OPCABG, the findings from ICG were significantly correlated with BNP levels and the results from echocardiography for the evaluation of cardiac hemodynamic changes. ICG might have a role in the assessment of cardiac function in clinical practice.