Oxidative stress and inflammasome activation in human rhabdomyolysis-induced acute kidney injury.
Free Radic Biol Med
; 160: 690-695, 2020 11 20.
Article
en En
| MEDLINE
| ID: mdl-32942024
ABSTRACT
Acute kidney injury (AKI) is a life-threatening complication of rhabdomyolysis. The pathophysiological mechanisms of rhabdomyolysis-induced AKI (RIAKI) have been extensively studied in the murine system, yet clinical translation of this knowledge to humans is lacking. In this study, we investigated the cellular and molecular pathways of human RIAKI. Renal biopsy tissue from a RIAKI patient was examined by quantitative immunohistochemistry (Q-IHC) and compared to healthy kidney cortical tissue. We identified myoglobin casts and uric acid localised to sites of histological tubular injury, consistent with the diagnosis of RIAKI. These pathological features were associated with tubular oxidative stress (4-hydroxynonenal staining), regulated necrosis/necroptosis (phosphorylated mixed-lineage kinase domain-like protein staining) and inflammation (tumour necrosis factor (TNF)-α staining). Expression of these markers was significantly elevated in the RIAKI tissue compared to the healthy control. A tubulointerstitial inflammatory infiltrate accumulated adjacent to these sites of RIAKI oxidative injury, consisting of macrophages (CD68), dendritic cells (CD1c) and T lymphocytes (CD3). Foci of inflammasome activation were co-localised with these immune cell infiltrate, with significantly increased staining for adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) and active caspase-1 in the RIAKI tissue compared to the healthy control. Our clinical findings identify multiple pathophysiological pathways previously only reported in murine RIAKI, providing first evidence in humans linking deposition of myoglobin and presence of uric acid to tubular oxidative stress/necroptosis, inflammasome activation and necroinflammation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Rabdomiólisis
/
Lesión Renal Aguda
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia