%0 Journal Article
%T Klotho deficiency aggravates sepsis-related multiple organ dysfunction | APSselect
%A Crist¨®foro Scavone
%A Denise M. A. C. Malheiros
%A Fern
%A Larissa de S¨¢ Lima
%A Le
%A Lect¨ªcia B. Jorge
%A Lucia Andrade
%A Makoto Kuro-o
%A Maria Irigoyen
%A Talita R. Sanches
%A [email protected]
%A a O. Coelho
%A o dos Santos
%A ro Ezaquiel de Souza
%J American Journal of Physiology-Renal Physiology
%D 2019
%X Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP-Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP-Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-¦ÊB activation. It is noteworthy that CLP-Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprusside, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction, Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced
%U https://journals.physiology.org/doi/full/10.1152/ajprenal.00625.2017%40apsselect.2019.6.issue-2