Análise dos níveis de microalbuminúria e da resposta inflamatória em pacientes com Síndrome da Apneia Obstrutiva do Sono

• Ano de defesa: 2018
• Autor(a) principal: Ramos, Frederico Antonio Pereira [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/48912/001300002b667
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Sleep Apnea Syndromes; Albuminuria; Hypoxia; Cytokines; Renin-Angiotensin System; Síndromes Da Apneia Do Sono; Albuminúria; Hipóxia; Citocinas; Sistema Renina-Angiotensina
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6392997; https://repositorio.unifesp.br/handle/11600/52541

Obstructive Sleep Apnea Syndrome (OSAS) is characterized by increased respiratory effort, with consequent hypoxia, chronic sympathetic hyperactivity, oxidative stress, inflammation and endothelial damage. It is characterized by being a chronic inflammatory state that increases the risk of cardiovascular complications. The aim of this study was to evaluate the levels of microalbuminuria and the inflammatory response in patients with OSAS. It is a cross-sectional study with 65 adult subjects, 35 with OSAS and 30 controls. The group of patients with OSAS was divided into two groups: 24 non-severe PAH (Apnea-hypopnea index - AHI <30/hour) and 9 severe PAH (AHI> 30/hour). Peripheral blood and urine from patients and controls were collected. Serum and urinary concentrations of IL-2, IL-4, IL-6, IL-17A, IFN-γ, TNF-α and IL-10 were detected by Cytometric Bead Array. The activity of Angiotensin converting enzyme (ACE), Renin and ACE2 in serum was determined by spectrofluorimetrically. Mann-Whitney and Kruskal-Wallis tests were used for analysis of medians between two and three or more groups, respectively. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the best accuracy of each cytokine and the severity of OSAS. It was considered significant p <0.05. In serum cytokine analysis, elevated levels of IL17A and IL6 were observed in patients with severe and non-severe OSAS when compared to controls (p <0.0001), in the OSAS group with C-reactive protein (CRP) ≥ 3mg/L when compared to the <3mg/L group (p <0.05). Elevated serum levels of IL6 in patients with indices of desaturation (ID) ≥ 16 when compared to the ID <16 group (p = 0.02). It was observed statistical difference in the urinary TNF levels between severe and non-severe SAOS groups (p = 0.01) and severe OSAS and controls (p = 0.0004). It was statistical difference in the urinary IL10 levels between patients OSAS and controls (p = 0.005). Patients with severe OSAS presented elevated urinary IL17A levels when compared to non-severe (p = 0.0008) and controls (p <0.0001), and elevated IL17A levels in the non-severe group when compared to controls (p = 0.003) . Patients with OSAS had high urinary IFN-γ levels when compared to controls (p <0.0001). In the analysis of urine cytokines by ID, elevated levels of IL-6 (p = 0.009), TNF-α(p = 0.005), IL-10 (p = 0.003), IL- (P = 0.001) and IL-4 (p = 0.01) in the ID ≥ 16 when compared to the group with ID <16. High urinary levels of IL6 (p = 0.001), IL-10 (p = 0.008), IL-12 (p = 0.01), IL-17A (p = 0.0002) , IFN-γ (p = 0.0009) and IL-4 (p = 0.01) in OSAS patients with CRP <3mg/L when compared to the group with CRP ≥ 3mg/L. In the analysis of serum levels of Creactive protein, the OSAS patients presented high levels of CRP when compared to controls (p = 0.02). The albumin/creatinine urinary ratio was elevated (7.1 mg / g, 5.2-9.1) in the patients compared to the controls (4.0 mg / g, 3-5.8, p = 0.001). Patients with severe OSAS have reduced levels of Z-Phe and HHL when compared to nonsevere and control groups. Regarding serum ACE2 levels, there was no significant difference between the groups. Renin serum levels were elevated in severe OSAS when compared to non-severe and control groups (p <0.0001). It is concluded that OSAS has a Th1 and Th17 immune response profile, and that the inflammatory process can cause endothelial lesion and hyperactivity of the RAS, with possible stimulus to the counterregulatory action by ECA2.