RESUMO
INTRODUCTION: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. RESEARCH DESIGN AND METHODS: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. RESULTS: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. CONCLUSIONS: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD. TRIAL REGISTRATION NUMBER: UMIN000011525.
Assuntos
Enzima de Conversão de Angiotensina 2 , Biomarcadores , Nefropatias Diabéticas , Taxa de Filtração Glomerular , Peptidil Dipeptidase A , Humanos , Masculino , Feminino , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/diagnóstico , Enzima de Conversão de Angiotensina 2/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Idoso , Prognóstico , Progressão da Doença , SeguimentosRESUMO
Marked Streptococcus pneumoniae tolerance is attributed to a penicillin and macrolide resistance genotypes, yet no report has, to our knowledge, compared the ability of these two genotypes to grow. Deviations in the number of clinical appearances of Streptococcus pneumoniae depend on the combination of these genotypes, thought primarily due to the individual strain growth. To test this, we compared ATCC6303 and a strain of each genotype with an absorption spectrophotometer. Time points-T0, T2, T4, T8, T10, T12, and T24-were compared to each of the following factors: initial value, dullness time, doubling time (D.B.T.), peak attainment, peak value, and stationary value. ATCC6303 and the clinical strain (PSSP8) showed no difference in time points or tested factors. Penicillin susceptible Streptcoccus pneumoniae (PSSP) 8 and Penicillin intermediately resistant Streptcoccus pneumoniae (PISP) (2b, mefA) strains showed significant differences in some time pointsT8, T10, and T12-and in certain factors-dullness time, D.B.T., and peak attainment-. In penicillin-resistant genotypes, the sequential growth rate priority was PSSP>PISP>PRSP, while in macrolide-resistant genotypes, it was mefA>non-mefA, and non-ermB>ermB. PISP (2x) and PISP (2x+2b, mefA) begin doubling immediately, suggesting that they proliferate earlier than other strains. Differences in the start of doubling time and doubling speed suggest that different strains are distributed among clinical resistant S. pneumoniae strains.