Roles of clusterin and IL-۱۸ reflected kidney injury in leptospirosis

Background and Aim : Leptospirosis is a zoonosis caused by infection with pathogenic strains of the bacterium Leptospira. Clusterin may play an important role to chronic kidney inflammation. Interleukin ۱۸ (IL-۱۸) is a proinflammatory cytokine. In the kidney it is induced and cleaved mainly in the proximal tubules and released into the urine under different conditions of kidney injury. Serum creatinine is not an ideal marker of renal function in patients with acute kidney injury (AKI). Previous studies demonstrated that urinary IL-۱۸ is increased in AKI. Thus, whether urine IL-۱۸ is an early diagnostic marker of AKI was investigated Urinary IL-۱۸ is a useful biomarker of AKI with moderate predictive value across all clinical settings. In this study, researchers aimed to investigate roles and levels of clusterin and IL-۱۸ reflected kidney injury in leptospirosisMethods : Tissue damage was examined by histology, infiltrate phenotypes by flow cytometry analysis, and fibrosis-related gene expression by PCR array then we studied the renal alterations in relation with the regulation of inflammatory cytokines and chemokines, comparing two experimental models of chronic leptospirosis, the Mice that survived the infection, becoming carrier of virulent leptospires, and the OF۱ mouse, a usual reservoir of the bacteria. Animals were monitored until ۲۸ days after injection with a virulent L. borgpetersenii serogroup Ballum to assess chronic infectionResults : Mice developed morphological changes such as tubulointerstitial nephritis and fibrosis. lower expression levels of cytokins indicated a better regulation of the inflammatory response and possible resolution processes likely related to resistance mechanisms. PCR array showed the association of clusterine deficiency with up-regulation of CCL۱۲, Col۳a۱, MMP۹ and TIMP۱ and down-regulation of EGF in kidneys.Conclusion : : Our data suggest that clusterine deficiency worsens renal inflammation and tissue fibrosis. Urinary IL-۱۸ is a useful biomarker of AKI with moderate predictive value across all clinical settings. Urine IL-۱۸ levels of >۱۰۰ pg/ml are associated with increased odds of AKI of ۶.۵ (۹۵% confidence interval ۲.۱ to ۲۰.۴) in the next ۲۴ h., urine IL-۱۸ predict AKI in the next ۲۴ h. The urine IL-۱۸ values were also significantly different between survivors and nonsurvivors (P < ۰.۰۵), and on multivariable analysis, the urine IL-۱۸ value on day ۰ is an independent predictor of mortality.

کلیدواژه ها:

leptospirosis ، interleukin ۱۸ (IL-۱۸) ، clusterin ، kidney ، AKI