RESUMO
Increased body weight (BW) induces inappropriate renin-angiotensin system (RAS) activation. The activation of the intrarenal RAS is associated with increased urinary angiotensinogen (uAGT), blood pressure (BP), and kidney damage. Here, we examined uAGT excretion levels in young non-diabetic human subjects with overweight (OW) and non-diabetic mice with high-fat diet (HFD)-induced OW. Human subjects (women and men; 20-28 years old) included two groups: (a) overweight (OW, n = 17, BMI ≥ 25); and (b) controls (normal weight (NW; n = 26, BMI ≤ 25). In these subjects, we measured BP, albuminuria, and protein levels of uAGT by ELISA adjusted by urinary creatinine (expressed by uAGT/uCrea). Mice (female and male C57BL/6J mice, 8 ± 2 weeks of age) also included two groups: HFD or normal fat diet (NFD) fed for 8 weeks. We measured BW, fasting blood glucose (FBG), BP by telemetry, albuminuria, and uAGT by ELISA. In humans: (i) no significant changes were observed in BP, albuminuria, and FBG when comparing NW and OW subjects; (ii) multivariate logistic regression analysis of independent predictors related to uAGT/uCrea levels demonstrated a strong association between uAGT and overweight; (iii) urinary reactive oxygen species (ROS) were augmented in men and women with OW; (iv) the uAGT/uCrea ratio was higher in men with OW. However, the uAGT/uCrea values were lower in women even with OW. In mice: (i) males fed an HFD for 8 weeks became OW while females did not; (ii) no changes were observed either in FBG, BP, or albuminuria; (iii) kidney ROS were augmented in OW male mice after 28 weeks but not in females; (iv) OW male mice showed augmented excretion of uAGT but this was undetectable in females fed either NFD or HFD. In humans and mice who are OW, the urinary excretion of AGT differs between males and females and overcomes overt albuminuria.
Assuntos
Angiotensinogênio , Sobrepeso , Sistema Renina-Angiotensina , Caracteres Sexuais , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Adulto Jovem , Albuminúria , Angiotensinogênio/urina , Camundongos Endogâmicos C57BL , Espécies Reativas de OxigênioRESUMO
OBJECTIVE: The delayed increase in serum creatinine levels poses challenges in the timely diagnosis of acute kidney injury. This study aimed to investigate the relationship between serum angiotensinogen and urinary angiotensinogen levels and the prognosis of renal function in patients diagnosed with acute kidney injury. METHODS: A total of 79 newly diagnosed acute kidney injury patients aged 18 years and older were enrolled. Serum angiotensinogen and urinary angiotensinogen levels were measured at the onset of the disease, as well as on the 15th and 30th days of follow-up. After 3 months, renal function was evaluated by measuring serum creatinine levels. RESULTS: Among the acute kidney injury patients, those in Kidney Disease: Improving Global Outcomes stage 3 exhibited significantly higher urinary angiotensinogen/urine creatinine levels compared with stages 1 and 2 patients at the time of diagnosis (p<0.05). Furthermore, a positive correlation was observed between the urinary angiotensinogen/urine creatinine level at the time of diagnosis and the serum creatinine level at the third month (r=0.408, p=0.048). CONCLUSION: The findings suggest that urinary angiotensinogen levels can serve as an indicator of the severity of acute kidney injury. Monitoring urinary angiotensinogen levels could potentially contribute to the prognosis assessment and management of acute kidney injury patients.