Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPJORGE, Lecticia B.COELHO, Fernanda O.SANCHES, Talita R.MALHEIROS, Denise M. A. C.SOUZA, Leandro Ezaquiel deSANTOS, Fernando dosLIMA, Larissa de SaSCAVONE, CristoforoIRIGOYEN, MariaKURO-O, MakotoANDRADE, Lucia2019-05-302019-05-302019AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.316, n.3, p.F438-F448, 20191931-857Xhttps://observatorio.fm.usp.br/handle/OPI/31828Sepsis-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-KB activation. It is noteworthy that CLP-Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprussidc, 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.engrestrictedAccessacute kidney injuryautonomic disorderKlothomultiple organ dysfunctionsepsisacute kidney injurynf-kappa-bacute-renal-failurenitric-oxide synthasespectral-analysisalpha-klothoheart-rateapoptosisbiomarkerexpressionarticleCopyright AMER PHYSIOLOGICAL SOC10.1152/ajprenal.00625.2017PhysiologyUrology & Nephrology1522-1466