Determinantes genéticos e ambientais das doenças hipertensivas da gravidez

The development of complex diseases such as preeclampsia are determined by both environmental and genetic factors, but there is also interaction among these factors. Preeclampsia is a pregnancy-specific disorder characterized by de-novo hypertension and proteinuria after 20th week of gestation. There is a broad spectrum of clinical presentations related to hypertensive disorders of pregnancy (HDP) that can range from mild preeclampsia to eclampsia (seizures) or HELLP syndrome (Hemolysis, Elevation of Liver enzymes, Low Platelets). Those clinical outcomes might be linked to different pathological mechanisms. Our work aims to identify factors (i.e. genes and environmental) associated with the HDP’s clinical spectrum. Using a case-control approach, we selected a total of 1498 pregnant women for epidemiological and genetic studies, encompassing 755 normotensive (control); 518 preeclampsia; 84 eclampsia; and 141 HELLP. Women were genotyped for 18 SNPs across 5 candidate genes (FLT1, ACVR2A, ERAP1, ERAP2 and LNPEP). For the environmental factors, we found maternal age, parity status and pre-gestational body mass index as important risk factors associated with disease. Genes were associated in a phenotype-specific manner: ACVR2A with early preeclampsia (rs1424954, p=0.002); FLT1 with HELLP syndrome (rs9513095, p=0.003); and ERAP1 with eclampsia (rs30187, p=0.03). Our results suggest that different genetic mechanisms along with specific environmental factors might determine the clinical spectrum of HDP. In addition, phenotype refinement seems to be an essential step in the search for complex disease genes

Conhecimento da doença renal crônica entre médicos conforme as diretrizes práticas

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem, with increasing prevalence in its terminal stage and one of the factors that can contribute is the failure to recognize the disease and its risk factors. OBJECTIVE: To evaluate the knowledge of medical residents (MR) and medical preceptors (MP) in hospitals in the Federal University of Rio Grande do Norte in Natal-RN - Brazil, on the DRC, based on the policy of the Kidney Disease Improving Global Outcomes (KDIGO ). METHODS: Cross-sectional study where 64 MR (R1 = 32; R2 = 15; R3 = 17) and 63 MP answered a questionnaire divided into seven sessions that addressed aspects of the DRC since the setting up referral to a nephrologist. RESULTS: Only 20 participants (15.7%) reported using any guidelines for the management of CKD. The scores obtained by session were: Definition and classification (46.1 ± 47.8); Risk factors (70.5 ± 27.9); Laboratory evaluation (58.2 ± 8.8); Clinical action plan (57.6 ± 19.9); Reduction in proteinuria (68.3 ± 15.0); Complications (64.8 ± 19.9); Referral to a nephrologist (73.0 ± 44.6). There was a statistically significant difference between the knowledge of MR and MP in the sessions: Laboratory evaluation (MR 61.5 ± 8.4 vs 54.8 ± 7.9 MP; p <0.001); Reduction in proteinuria (73.1 ± 11.4 vs MR MP 63.5 ± 16.7; p <0.001) and Referral to a nephrologist (MR 81.2 ± 39.3 vs 64.5 ± 48.2 MP; p = 0.035). Among the MR, the R2 obtained the best score (63.9 ± 22.6 vs R1 R2 R3 71.9 ± 17.2 vs 63.5 ± 22.5, p = 0.445). It identified a low percentage of success of the doctors on the definition of CKD (MP = 46%; R1 = 40.6%; R2 = 60%; R3 = 52.9%; p = 0.623) and classification (MP = 34.9%; R1 = 53.1%, R2 = 60%; R3 = 52.9%; p = 0.158). CONCLUSION: The study showed that most doctors do not use any guidelines for clinical management of CKD and that there are gaps in knowledge on the subject, even among physicians who work in the university environment. In this sense, we propose the realization of mini-workshops for participants and students from boarding UFRN, using Case-Based Learning Strategy (CBL), with small group discussion, to strengthen the incorporation of CKD guidelines in undergraduate teaching and in clinical medical practice in general.

Conhecimento da doença renal crônica entre médicos conforme as diretrizes práticas

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem, with increasing prevalence in its terminal stage and one of the factors that can contribute is the failure to recognize the disease and its risk factors. OBJECTIVE: To evaluate the knowledge of medical residents (MR) and medical preceptors (MP) in hospitals in the Federal University of Rio Grande do Norte in Natal-RN - Brazil, on the DRC, based on the policy of the Kidney Disease Improving Global Outcomes (KDIGO ). METHODS: Cross-sectional study where 64 MR (R1 = 32; R2 = 15; R3 = 17) and 63 MP answered a questionnaire divided into seven sessions that addressed aspects of the DRC since the setting up referral to a nephrologist. RESULTS: Only 20 participants (15.7%) reported using any guidelines for the management of CKD. The scores obtained by session were: Definition and classification (46.1 ± 47.8); Risk factors (70.5 ± 27.9); Laboratory evaluation (58.2 ± 8.8); Clinical action plan (57.6 ± 19.9); Reduction in proteinuria (68.3 ± 15.0); Complications (64.8 ± 19.9); Referral to a nephrologist (73.0 ± 44.6). There was a statistically significant difference between the knowledge of MR and MP in the sessions: Laboratory evaluation (MR 61.5 ± 8.4 vs 54.8 ± 7.9 MP; p <0.001); Reduction in proteinuria (73.1 ± 11.4 vs MR MP 63.5 ± 16.7; p <0.001) and Referral to a nephrologist (MR 81.2 ± 39.3 vs 64.5 ± 48.2 MP; p = 0.035). Among the MR, the R2 obtained the best score (63.9 ± 22.6 vs R1 R2 R3 71.9 ± 17.2 vs 63.5 ± 22.5, p = 0.445). It identified a low percentage of success of the doctors on the definition of CKD (MP = 46%; R1 = 40.6%; R2 = 60%; R3 = 52.9%; p = 0.623) and classification (MP = 34.9%; R1 = 53.1%, R2 = 60%; R3 = 52.9%; p = 0.158). CONCLUSION: The study showed that most doctors do not use any guidelines for clinical management of CKD and that there are gaps in knowledge on the subject, even among physicians who work in the university environment. In this sense, we propose the realization of mini-workshops for participants and students from boarding UFRN, using Case-Based Learning Strategy (CBL), with small group discussion, to strengthen the incorporation of CKD guidelines in undergraduate teaching and in clinical medical practice in general.

Receptores de citocinas proinflamatórias na pré-eclâmpsia

Preeclampsia is a disease specific of human pregnancy that affects 3-8% of pregnant women, and it is one of the three leading causes of maternal mortality and morbidity. The disease is characterized by hypertension and proteinuria after the 20th week of gestation. The risk factors for this disease are not completely understood but appear to include dysregulation of the immune response arising from defects in placentation, environmental and genetic factors. This study aimed to determine whether the variation in the amount of proinflammatory cytokine receptors IL-1R2, IL-6R and TNF-αR1 would be involved in preeclampsia. They were recruited women with preeclampsia (n=24) and women who evolved during pregnancy without changes in blood pressure (n=12) were recruited. Clinical and laboratory data were collected. The cytokine receptors (IL-1R2, TNF-αR1 and IL-6R) were assessed in mononuclear cells isolated from peripheral blood using flow cytometry (Control = 8; PE = 24). C-reactive protein (CRP) was determined by CRP ultrasensitive method (Control = 7; PE = 18) was performed using sera pregnant women. Women with preeclampsia had higher weight at the beginning of the pregnancy (p=0.0171) and lower gestational age at delivery (0.0008). Classical monocytes were decreased in preeclampsia but not intermediate or non-classical monocytes. The frequency of IL-1R2 pro inflammatory cytokine receptors is decreased in women with PE only in the subpopulation of non-classical monocytes (p = 0.0011). TNF-αR1 receptor and IL-6R, had a decreased frequency in the three subpopulations of monocyte (classic, intermediate and non-classical) when compared to women with normal pregnancy. An increase in IL-1R2 receptor in TCD4+ lymphocytes, but a decrease in TNF-receptor and IL-6R in women with preeclampsia were found. No differences in the frequency of those receptors in CD3+/CD8+ in preeclampsia. There was no difference in C-reactive protein in preeclampsia. The reduction in the amount of IL-1R2, TNF- αR1 and IL-6R monocytes and lymphocytes can be involved in the regulation of inflammation observed in preeclampsia, contributing to disease.