Butyrate treatment for acute kidney injury

• Autores: Chiara Favero
• Directores de la Tesis: M. Dolores Sánchez Niño (dir. tes.), Alberto Ortiz Arduan (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2024
• Idioma: inglés
• Número de páginas: 112
• Títulos paralelos:
  • El butirato como tratamiento en el fracaso renal agudo
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • Acute kidney injury (AKI) is a heterogeneous group of conditions characterized by a sudden and abrupt decline in kidney function. AKI is common in hospitalized patients and increases short term and long term mortality.

    There are no treatment options availa ble for AKI, other than replacing kidney function.

    Gut microbiota products such as the short chain fatty acid butyrate have anti inflammatory actions that may protect tissues, including the kidney, from injury. However, the molecular mechanisms of kidney tissue protection by butyrate are poorly understood.

    Treatment with oral butyrate for two weeks prior to cisplatin AKI and during AKI improved the kidney function while stopping butyrate before AKI was not protective. Continuous butyrate preserved the expression of kidney protective factors such as Klotho, P GC 1 α and NLRP6 which were otherwise downregulated.

    Kidney protection afforded by this continuous butyrate schedule was confirmed in a second model of nephrotoxic AKI, folic acid AKI. Butyrate decreased the kidney inflammation that is otherwise upregulated and preserved the expression of kidney protective f actors.

    To assess the contribution of preservation of kidney protective factors to kidney resilience, recombinant Klotho was administered to mice with cisplatin AKI and shown to preserve the expression of PGC 1 α and NLRP6, to decrease kidney inflammation and to protect from AKI.

    In cultured tubular cells, butyrate dampened the maladaptive tubular cell response to a proinflammatory milieu, preserving the expression of kidney protective factors. Butyrate protection was confirmed in kidney on chip bioengineered human tubular cells.

    Butyrate behaved as a histone deacetylase inhibitor and inhibited the NF kB and MAP kinase pathways in vivo, but histone deacetylase inhibition was the main mechanism of action in cultured tubular cells.

    In conclusion, butyrate promoted kidney resilience to AKI, decreasing the inflammation and preserving the downregulation of kidney protective genes such as Klotho. It might act inhibiting NF kB and MAP kinase pathways and as deacetylase inhibitor.

    This information may be clinically relevant, given the widespread use of antibiotics in hospitalized patients, which is expected to negatively impact the gut microbiota and butyrate production