RESUMEN
OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.
Asunto(s)
Complemento C3 , Factor H de Complemento , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Complemento C3/metabolismo , Complemento C3/análisis , Factores de Riesgo , Anciano , Adulto , Hipertensión/complicaciones , Hipertensión/sangre , Activación de Complemento , Hipertensión Esencial/sangre , Hipertensión Esencial/complicaciones , Hipertensión Esencial/fisiopatología , Modelos Logísticos , Vía Alternativa del Complemento , Progresión de la EnfermedadRESUMEN
PURPOSE: To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism. METHODS: Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats. RESULTS: A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation. CONCLUSION: Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.