Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial.

AIMS: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. METHODS: In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. RESULTS: Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. CONCLUSIONS: Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. TRIAL REGISTRATION: Clinical trials registration number: NCT00971165.

Fluid overload is associated with use of a higher number of antihypertensive drugs in hemodialysis patients.

INTRODUCTION: Hypertension is multifactorial, highly prevalent in the hemodialysis (HD) population and its adequate control requires, in addition to adequate volume management, often the use of multiple antihypertensive drugs. We aimed to describe the use of antihypertensive agents in a group of HD patients and to evaluate the factors associated with the use of multiple classes (≥3) of antihypertensives. METHODS: We analyzed the baseline data from the HDFit study. Clinically stable patients with HD vintage between 3 and 24 months without any severe mobility limitation were recruited from sites throughout southern Brazil. Fluid status was measured pre-dialysis with the Body Composition Monitor (BCM; Fresenius, Germany). Fluid overload (FO) was considered when the overhydration index (OH) was greater than 7% of extracellular water (OH/ECW > 7%) and overweight was defined as a body mass index (BMI) greater than 25 kg/m2 . Prescriptions of antihypertensive drugs were obtained from participants' reports and medical records. Logistic regression was employed to determine factors associated with excessive use of antihypertensive medication (≥3 classes). FINDINGS: Of 195 studied patients, 171 with complete data were included (70% male, 53 ± 15 years old, 57% of them with FO). Pre-dialysis systolic blood pressure (SBP) was 150 ± 24 mmHg and patients used a median of 2 (1-3) antihypertensive drugs. Vasodilators (20%) were of lowest prevalence, use of other classes varied from 40% to 53%. Sixty-two (36%) subjects used ≥3 classes and presented a higher prevalence of diabetes and FO, lower prevalence of overweight, and higher SBP. In a logistic regression model age, BMI <25 kg/m2 , and OH/ECW > 7% were associated with excessive drug use. DISCUSSION: More than one-third of participants used ≥3 classes of antihypertensive drugs, and it was associated with older age, BMI <25 kg/m2 and FO. Strategies that better manage FO may aid better blood pressure control and avoid the use of multiple antihypertensive medications.

Increased proteinuria and uric acid levels are associated with eclamptic crisis.

OBJECTIVES: Eclampsia results in high morbidity and mortality, so it is important to identify clinical and laboratorial aspects that may be useful as potential markers to differentiate women at higher risk. Thus, we aim to identify, among women with preeclampsia, aspects that may increase the risk to develop eclampsia. STUDY DESIGN: Retrospective cohort study. The records of patients delivered at Hospital São Lucas/PUCRS were reviewed retrospectively; 733 pregnant women with hypertension were analyzed; 329 had preeclampsia, and 45 eclampsia. MAIN OUTCOME MEASURES: Serum uric acid levels and protein excretion in women that develop eclampsia. RESULTS: Patients with eclampsia had higher serum uric acid levels and protein excretion, systolic and diastolic blood pressure; were more likely to have cesarean section and had worst perinatal outcomes. The combination of uric acid above 5.9 mg/dL and protein/creatinine ratio over 4.9 had a striking association with eclampsia (p ≤ 0.001). The occurrence of HELLP syndrome was significantly different between groups, with a higher incidence among women who developed eclampsia (OR 6.5; 95%CI, 3.2-13.2; p < 0.001). CONCLUSION: Our data suggest that the combination of high levels of maternal serum uric acid and proteinuria are strongly associated with the development of eclamptic crises.

Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial.

BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. METHODS: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. RESULTS: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. CONCLUSION: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.

Disinfection of the peritoneal dialysis bag medication port: Comparison of disinfectant agent and disinfection time.

AIM: The aim of the present study was to compare different disinfection techniques for the peritoneal dialysis bag medication port (MP). METHODS: An experimental study was conducted testing different cleaning agents (70% alcohol vs 2% chlorhexidine) and time periods (5, 10 and 60 s) for disinfection of the MP. Five microorganisms (S. aureus, E. coli, A. baumannii and C. parapsilosis, CNS) were prepared for use as contaminants of the MP. MP were incubated in Tryptic soy broth at 36°C for 24 h, after which, they were seeded on a Biomérieux blood agar plate and incubated for 24 h at 36°C. RESULTS: Three hundred peritoneal dialysis bags were analyzed regarding the time expose to the disinfectant showed a statistically significant difference in the number of culture positive (7/100) P = 0.001; Gram positive (6/100) P = 0.006 for 5 s, one positive culture and turbid bag with 10 s, while friction for 60 s showed all negative results. The comparison between disinfectant, alcohol or chlorhexidine, 150 bag in each group, showed that the ones disinfected with alcohol had five turbid bags, eight positive cultures and seven germs identified, while all bags disinfected with chlorhexidine were negative for all parameters, with a difference statistically significant (P = 0.004). CONCLUSION: Our results suggest that the MP should be scrubbed with 2% chlorhexidine for at least 5 s; if alcohol 70% is used the length of friction should not be inferior to 10 s.

Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial.

BACKGROUND: Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. METHODS AND RESULTS: This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). CONCLUSIONS: A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR-74rr6s.

Comparison of the Schwartz and CKD-EPI Equations for Estimating Glomerular Filtration Rate in Children, Adolescents, and Adults: A Retrospective Cross-Sectional Study.

BACKGROUND: Estimating kidney glomerular filtration rate (GFR) is of utmost importance in many clinical conditions. However, very few studies have evaluated the performance of GFR estimating equations over all ages and degrees of kidney impairment. We evaluated the reliability of two major equations for GFR estimation, the CKD-EPI and Schwartz equations, with urinary clearance of inulin as gold standard. METHODS AND FINDINGS: The study included 10,610 participants referred to the Renal and Metabolic Function Exploration Unit of Edouard Herriot Hospital (Lyon, France). GFR was measured by urinary inulin clearance (only first measurement kept for analysis) then estimated with isotope dilution mass spectrometry (IDMS)-traceable CKD-EPI and Schwartz equations. The participants' ages ranged from 3 to 90 y, and the measured GFRs from 3 to 160 ml/min/1.73 m2. A linear mixed-effects model was used to model the bias (mean ratio of estimated GFR to measured GFR). Equation reliability was also assessed using precision (interquartile range [IQR] of the ratio) and accuracy (percentage of estimated GFRs within the 10% [P10] and 30% [P30] limits above and below the measured GFR). In the whole sample, the mean ratio with the CKD-EPI equation was significantly higher than that with the Schwartz equation (1.17 [95% CI 1.16; 1.18] versus 1.08 [95% CI 1.07; 1.09], p < 0.001, t-test). At GFR values of 60-89 ml/min/1.73 m2, the mean ratios with the Schwartz equation were closer to 1 than the mean ratios with the CKD-EPI equation whatever the age class (1.02 [95% CI 1.01; 1.03] versus 1.15 [95% CI 1.13; 1.16], p < 0.001, t-test). In young adults (18-40 y), the Schwartz equation had a better precision and was also more accurate than the CKD-EPI equation at GFR values under 60 ml/min/1.73 m2 (IQR: 0.32 [95% CI 0.28; 0.33] versus 0.40 [95% CI 0.36; 0.44]; P30: 81.4 [95% CI 78.1; 84.7] versus 63.8 [95% CI 59.7; 68.0]) and also at GFR values of 60-89 ml/min/1.73 m2. In all patients aged ≥65 y, the CKD-EPI equation performed better than the Schwartz equation (IQR: 0.33 [95% CI 0.31; 0.34] versus 0.40 [95% CI 0.38; 0.41]; P30: 77.6 [95% CI 75.7; 79.5] versus 67.5 [95% CI 65.4; 69.7], respectively). In children and adolescents (2-17 y), the Schwartz equation was superior to the CKD-EPI equation (IQR: 0.23 [95% CI 0.21; 0.24] versus 0.33 [95% CI 0.31; 0.34]; P30: 88.6 [95% CI 86.7; 90.4] versus 29.4 [95% CI 26.8; 32.0]). This study is limited by its retrospective design, single-center setting with few non-white patients, and small number of patients with severe chronic kidney disease. CONCLUSIONS: The results from this study suggest that the Schwartz equation may be more reliable than the CKD-EPI equation for estimating GFR in children and adolescents and in adults with mild to moderate kidney impairment up to age 40 y.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.

OBJECTIVES: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. METHODS: In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. RESULTS: The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ±â€Š40.4 versus 16.2 ±â€Š26.7 mg, P = 0.09). CONCLUSION: Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. CLINICAL TRIALS REGISTRATION NUMBER: NCT00971165.

Immature platelet fraction in hypertensive pregnancy.

BACKGROUND: Imbalance in hemostatic mechanisms can occur during pregnancy with a tendency for hypercoagulability and increased thrombosis risk. Pregnant women with hypertensive disorder, especially preeclampsia, show alterations in platelet indexes. Immature platelet fraction (IPF) has been suggested as a sensitive index for monitoring changes in platelet production and destruction. OBJECTIVES: To evaluate the IPF in patients diagnosed with a gestational hypertensive disorder (GHD). PATIENTS AND METHODS: A cross-sectional study was conducted at an University Hospital to estimate maternal blood IPF index in 99 pregnant women, divided into three groups: normotensive pregnancy (NP), preeclampsia syndrome (PES), and non-proteinuric hypertensive pregnancy (nPHP). Following ethical approval and written informed consent, samples were collected from 33 NP, 34 PES, and 32 nPHP women. Platelet indexes were measured by fluorescent flow cytometry. RESULTS: IPF and mean platelet volume (MPV) counts in GHD were significantly higher than in NP (IPF: 3.8, 2.4-5.1%; 8.6, 5.8-10.6%; 7.3, 4.2-10.2%; p < 0.001 and MPV: 10.6 ± 0.9 fL; 12.1 ± 1.0 fL; 11.6 ± 1.0 fL; p < 0.001 for NP, PES, and nPHP, respectively). No difference was detected between PES and nPHP groups. The distribution of patients with an IPF above 6.1%for NP, PES, and nPHP was 9%, 65%, and 43.8%, respectively (p < 0.001). IPF as a test to differentiate GHD from the controls achieved an area under the curve of 0.83 on a receiver operating characteristics curve. CONCLUSION: A distinct profile in platelet indexes was detected in hypertensive pregnancies. It suggests that these markers could be used in daily routine as an additional tool in the management of pregnant women.

Endocan-1 concentrations in maternal and fetal plasma and placentae in pre-eclampsia in the third trimester of pregnancy.

INTRODUCTION: Endocan-1 has been proposed as a possible biomarker and predictor of vascular endothelial related pathologies. Thus, we hypothesised that Endocan-1 levels would be up-regulated in maternal plasma and placentae from women with pre-eclampsia. The aim of our study was to compare Endocan-1 concentrations in maternal/fetal plasma and placentae from normotensive and pre-eclamptic pregnancies. METHODS: Observational and case-controlled study, at the São Lucas Hospital, Brazil. Placental biopsies, maternal/umbilical venous (fetal) plasma were taken from 67 normotensive and 50 pre-eclamptic women. Endocan-1 levels were quantified using MagPlex(TH)-C and analysed by Analysis of Covariance and Pearson correlation. The null hypothesis was rejected at p<0.05. RESULTS: Higher levels of Endocan-1 were found in maternal plasma in the pre-eclamptic group (mean ratio=1.49; 95% confidence interval: 1.19-1.85, p=0.001), with a moderate effect size (Cohen's D=0.84). Placental Endocan-1 levels (µg/g) were lower in pre-eclampsia (1.52 [1.10, 2.40] vs. 2.24 [1.32, 3.75], p=0.033) and fetal Endocan-1 concentration (ng/ml) did not show any difference between groups (3.10 [2.60, 4.54] vs. 2.91 [2.20, 3.66] p=0.085). In addition, an up-regulation of maternal plasma Endocan-1 in the pre-eclamptic group was observed when stratified in relation to gestational age, systolic blood pressure and proteinuria (p<0.05, for all). Furthermore, a positive correlation between Endocan-1 concentration in maternal vs. fetal plasma was also found (r=0.258, p=0.015). For the matched samples, a negative correlation between Endocan-1 in maternal/fetal plasma with birthweights, placental weights and gestational age at delivery was observed (p<0.05 for all). DISCUSSION: Endocan-1 is increased in women with pre-eclampsia for all strata, which highlight the importance of this molecule as a possible biomarker. The negative correlations between Endocan-1 and clinical data suggest that this molecule may also be involved with prematurity and low birth weight, which warrants further investigations.

Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor in which prognostic factors are still not well established. Programmed Death Ligand-1 (PD-L1) expression in ACC and its association with clinico-pathological features and survival outcomes are unknown. METHODS: Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 28 patients with ACC. PD-L1 expression was evaluated by immunohistochemistry (IHC) in both tumor cell membrane and tumor infiltrating mononuclear cells (TIMC). PD-L1 positivity on tumor cells was defined as ≥5% tumor cell membrane staining. TIMC were evaluated by IHC using a CD45 monoclonal antibody. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrates and percentage of positive cells was developed. Any score greater that zero was considered PD-L1 positive. Baseline clinico-pathological characteristics and follow up data were retrospectively collected. Comparisons between PD-L1 expression and clinico-pathological features were evaluated using unpaired t-test and Fisher's exact test. Kaplan-Meier method and log-rank test were used to assess association between PD-L1 expression and 5-year overall survival (OS). RESULTS: Among 28 patients with surgically treated ACC, 3 (10.7%) were considered PD-L1 positive on tumor cell membrane. On the other hand, PD-L1 expression in TIMC was performed in 27 specimens and PD-L1 positive staining was observed in 19 (70.4%) patients. PD-L1 positivity in either tumor cell membrane or TIMC was not significantly associated with higher stage at diagnosis, higher tumor grade, excessive hormone secretion, or OS. CONCLUSIONS: PD-L1 expression can exist in ACC in both tumor cell membrane and TIMC with no relationship to clinico-pathologic parameters or survival.

Is there any relationship between ABO/Rh blood group and patients with pre-eclampsia?

OBJECTIVES: The purpose of the present study was to evaluate the association between pre-eclampsia and blood groups in a group of pregnant women hospitalized in a University Hospital in Porto Alegre, Brazil - Hospital São Lucas (HSL)/PUCRS. STUDY DESIGN: Our sample consisted of 10,040 pregnant women admitted to the maternity department of HSL between 2005 and 2010. The patients were reviewed retrospectively for inclusion. Medical records of 414 women were diagnosed as preeclampsia/eclampsia and 9611 women were identified to the control group. The patients were divided into two groups: the group with preeclampsia/eclampsia and the control group, and their blood groups were considered. Data were analyzed using SPSS for Windows version 17.0. Categorical data were summarized by counts and percentages, with the statistical significance evaluated by the Chi-square test. The null hypothesis was rejected when p<0.05. MAIN OUTCOME MEASURES: Maternal parameters were compared between control group and pre-eclampsia, respectively, Systolic Blood Pressure (117±19.98 vs. 165±19.99); Diastolic Blood Pressure (73±14.23 vs. 106±14.24) and maternal weight at booking (73±33 vs. 83±33). For all data: mean+SD; p<0.05. In relation to blood groups, firstly they were stratified by Rh and ABO phenotypes, separately. After that the groups were put together. RESULTS: No differences in blood group distribution were observed between controls and pre-eclampsia for any analysis. (p>0.05). CONCLUSIONS: When we adopted stricter criteria for pre-eclampsia and a large sample from the same region we noted that the results did not show any association between blood groups and the development of pre-eclampsia.

Tratamento de hipertensão gestacional grave na urgência: revisão de diretrizes / Treatment of severe gestational hypertension in emergency: review of guidelines

A doença hipertensiva gestacional é uma das principais causas de morbimortalidade maternal no mundo. O tratamento definitivo depende do esvaziamento uterino. Medicamentos anti-hipertensivos buscam diminuir desfechos desfavoráveis para o binômio mãe-feto. O objetivo desse estudo de revisão foi comparar diferentes diretrizes sobre o tratamento de hipertensão gestacional, com o foco na conduta de urgência.

Hypertensive disorders during pregnancy are a major cause of maternal morbidity and mortality. Delivery is the definitive treatment. Antihypertensive drugs may reduce blood pressure levels and reduce adverse outcomes for both mother and fetus. The aim of this review was to compare different guidelines on the treatment of acute gestational hypertension.

Aumento dos níveis do receptor solúvel da Interleucina-6 em pacientes com pré-eclâmpsia em relação a gestantes normotensas / Increased levels of the soluble receptor of interleukin-6 in patients withpreeclampsia compared to normotensive pregnant women

Objetivos: Comparar níveis plasmáticos do receptor solúvel da interleucina-6 (IL-6sR) entre gestantes normotensas e com pré-eclâmpsia.Métodos: Realizou-se coleta de sangue materno no período pré-parto de 21 pacientes com pré-eclâmpsia e 39 controles normotensas. As amostras foram armazenadas a menos 80°C até a análise laboratorial. Os níveis séricos de IL-6sR foram mensurados através do teste imunoenzimático ELISA. Para comparar os grupos foi utilizado teste t de Student. Consideraram-se significantes os resultados com P menor do que 0,05.Resultados: Os dados de gestantes com pré-eclâmpsia e gestantes normotensas, respectivamente, foram: idade materna 22,3±4,8 vs 26,0±3,7 anos (P=0,06); idade gestacional 32,7±5,8 vs 40,1±0,8 semanas (P=0,01); pressão arterial sistólica 143,0±2,2 vs 118,8±3,1 mmHg (P=0,01); pressão arterial diastólica 112,5±4,0 vs 77,2±10,2 mmHg (P=0,01); ácido úrico 5,87±1,10 vs 4,57±0,12 mg/dL (P=0,02); creatinina 0,82±0,12 vs 0,73±0,09 mg/dL (P=0,01); peso do recém-nascido 2.130,7±839,3 vs 3.555,0±261,0 gramas (P=0.01) e peso da placenta 621,3±167,0 vs 796,3±154,2 gramas (P=0,05).A relação proteinúria/creatininúria no grupo das pacientes com pré-eclâmpsia foi de 2,40±1,31. O valor de IL-6sR(ng/dL) na pré-eclâmpsia foi 28,7±10,8 vs 16,5±6,4 na gestante normotensa (P=0,01).Conclusões: Estes resultados mostram o aumento dos níveis plasmáticos do IL-6sR em pacientes com pré-eclâmpsia, em relação a gestantes normotensas. Mais estudos se mostram necessários para o esclarecimento da fisiopatologia desta entidade, como a análise de outras citocinas ligadas a esse receptor, visto que elas podem ser a chave para a resposta inflamatória sistêmica que ocorre nestas pacientes e, portanto, para o seu tratamento...

Aims: To compare Interleukin-6 soluble receptor (IL-6sR) plasmatic levels between normotensive pregnant controls and preeclamptic women.Methods: Maternal blood samples were collected before delivery from 21 patients with preeclampsia and 39 normotensive pregnant controls. Samples were stored at -80°C until laboratory assay. IL-6sR was measured by ELISA enzyme immunoassay. To compare groups Student's t test was used. Results with P less than 0.05 were considered significant.Results: Data from preeclampsia and normotensive pregnant controls were respectively: maternal age 22.3±4.8 vs 26.0±3.7 years (P=0.06); gestational age 32.7±5.8 vs 40.1±0.8 weeks (P=0.01); systolic blood pressure 143.0±2.2 vs 118.8±3.1 mmHg (P=0.01); diastolic blood pressure 112.5±4.0 vs 77.2±10.2 mmHg (P=0.01); uric acid 5.87±1.10 vs4.57±0.12 mg/dL (P=0.02); creatinine 0.82±0.12 vs 0.73±0.09 mg/dL (P=0.01); birth weight 2130.7±839.3 vs 3555.0±261.0 g (P=0.01); placental weight 621.3±167.0 vs 796.3±154.2 g (P=0,05). Proteinuria over creatininuria ratio in the preeclampsia group was 2.40±1.31. The concentration of IL-6sR (ng/dL) was 28.7±10.8 in preeclampsia vs 16.5±6.4 in normotensive pregnant controls (P=0.01).Conclusions: These results show an increased plasma levels of IL-6sRin patients with preeclampsia compared to normotensive pregnant women. More studies are necessary to clarify the pathophysiology of this entity, including the analysis of other cytokines linked to this receptor, due to the fact that they can be the key for the systemic inflammatory response that occurs in these patients and therefore for their treatment....

Association of proteinuria threshold in pre-eclampsia with maternal and perinatal outcomes: a nested case control cohort of high risk women.

OBJECTIVES: To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499 mg and ≥500 mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension. DESIGN: Secondary analysis of the Vitamins in Pre-Eclampsia Trial. SETTING: 25 UK hospitals in ten geographical areas. POPULATION: 946 women with pre-existing risk factors for pre-eclampsia. METHODS: Women with pre-eclampsia and proteinuria 300-499 mg/24 h (PE300, referent group, n=60) or proteinuria ≥500 mg/24 h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110). MAIN OUTCOME MEASURES: MATERNAL: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5(th) centile, gestation at delivery. RESULTS: Severe hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P≤0.01) and GH (10%; p≤0.001). Gestation at delivery was earlier in PE500 (33.2 w) than PE300 (37.3 w; P≤0.001), and later in CHT (38.3 w; P≤0.05) and GH (39.1 w; P≤0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P≤0.001) and GH (16.5%; P≤0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001), and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05). CONCLUSION: Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500.

Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype.

Atherosis of spiral arteries in uteroplacental beds from preeclamptic women resemble those of atherosclerosis, characterized by increased plasma lipids and lipoproteins. We hypothesized that: 1) lipoprotein receptors/transporters in the placenta would be upregulated in preeclampsia, associated with increased maternal and fetal lipoprotein concentrations; and 2) expression of these would be reduced in preeclamptic placentae from women delivering small-for-gestational-age (SGA) infants. Placental biopsies and maternal and umbilical serum samples were taken from 27 normotensive and 24 preeclamptic women. Maternal/umbilical cord serum LDL, HDL, total cholesterol, and triglycerides were measured. Placental mRNA expression of lipoprotein receptors/transporters were quantified using quantitative RT-PCR. Protein localization/expression of LDL receptor-related protein 1 (LRP-1) in the preeclamptic placentae with/without SGA was measured by immunohistochemistry. Placental mRNA expression of all genes except paraoxonase-1 (PON-1), microsomal triglyceride transfer protein (MTTP), and protein disulfide isomerase family A member 2 (PDIA2) were observed. No differences for any lipoprotein receptors/transporters were found between groups; however, in the preeclamptic group placental LRP-1 expression was lower in SGA delivering mothers (n = 7; P = 0.036). LRP-1 protein was localized around fetal vessels and Hofbauer cells. This is the first detailed study of maternal/fetal lipoprotein concentrations and placental lipoprotein receptor mRNA expression in normotensive and preeclamptic pregnancies. These findings do not support a role of altered lipid metabolism in preeclampsia, but may be involved in fetal growth.

PP011. Placental expression of the major protein components of caveolae, eNOS and iNOS in pre-eclampsia.

INTRODUCTION: Caveolins and Cavins are the major protein components of caveolae and regulate many cardiovascular functions. Caveolin-1 inhibits eNOS activity. The possible regulation of vascular reactivity/blood pressure by the caveolae are of interest in relation to pre-eclampsia (PE). We hypothesised that expression of Caveolin/Cavin genes would be reduced, paralleling the up-regulated eNOS in PE compared to normotensive controls (NC). OBJECTIVES: To analyse the placental mRNA expression of Caveolins1-3 and, Cavins1-4, eNOS and iNOS; and protein of caveolin-1, cavin-1 and eNOS in NC and PE placentae from White European women. METHODS: Following ethical approval and informed written consent, placental biopsies were taken midway between the cord and periphery, avoiding infarcts, from 24 NC and 23 PE patients. Gene expression was measured by qRT-PCR. Protein localization was identified by immunohistochemistry and expression semi-quantitatively assessed. RESULTS: Results of mRNA/proteins are shown on table below. Protein expression was localised to the cytotrophoblast and syncytiotrophoblast. No differences were found for any other gene/protein. CONCLUSION: As well as their known effects on eNOS expression, caveolae mediate internalisation of numerous hormone receptors, thus potentially changing pressor and depressor responsiveness. This is the first time that structural determinants of caveolae have been studied in NC and PE pregnancy. FUNDING: Tommy's, CAPES.

Functional matrix metalloproteinase (MMP)-9 genetic variants modify the effects of hemodialysis on circulating MMP-9 levels.

BACKGROUND: Altered levels of matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in cardiovascular alterations associated with end stage kidney disease (ESKD). Genetic polymorphisms in MMP-9 gene affect MMP-9 levels. We examined how MMP-9 polymorphisms and haplotypes affect the changes in plasma MMP-9 and TIMP-1 levels found in patients with ESKD undergoing hemodialysis. METHODS: We studied 94 ESKD patients undergoing hemodialysis for at least 3 months. MMP-9 and TIMP-1 were measured by ELISA in plasma from blood samples collected before and after a session of hemodialysis. Genotypes for three MMP-9 polymorphisms (C(-1562)T, rs3918242; -90 (CA)(14-24), rs2234681; and Q279R, rs17576) were determined by Taqman® Allele Discrimination Assay and real-time polymerase chain reaction. Haplotype frequencies were determined with the software program PHASE 2.1. RESULTS: Hemodialysis increased MMP-9 and TIMP-1 levels (P<0.05). Genotypes had no effects on baseline MMP-9 and TIMP-1 levels (P>0.05). Hemodialysis increased MMP-9 and TIMP-1 levels in subjects with the CC (but not CT or TT) genotype for the C(-1562)T polymorphism (P<0.05), and increased MMP-9 levels in subjects with the QQ (but not QR or RR) genotype for the Q279R polymorphism (P<0.05), whereas the CA(n)(14-24) polymorphism had no major effects. While MMP-9 haplotypes had no effects on baseline MMP-9 levels (P>0.05), hemodialysis increased MMP-9 levels and MMP-9/TIMP-1 ratios in subjects carrying the CLQ haplotype (P=0.0012 and P=0.0045, respectively). CONCLUSION: ESKD patients with the QQ genotype for the Q279R polymorphism or with the CLQ haplotype are exposed to more severe increases in MMP-9 levels after hemodialysis. Such patients may benefit from the use of MMP inhibitors.