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.

Serum tissue factor as a biomarker for renal clear cell carcinoma.

PURPOSE: to determine the usefulness of serum TF as a potential marker for patients with clear cell RCC. MATERIALS AND METHODS: prospective study of 30 patients with clear cell RCC submitted to nephrectomy and 16 controls without clear cell RCC treated surgically for other conditions. TF is a endothelium marker that was correlated with worse prognosis in a variety of solid tumors including RCC. Serum TF was collected before surgery at the operating room and in the postoperative setting after at least four weeks. Serum samples were analyzed with a commercial ELISA kit for human TF (R&D Systems®). RESULTS: Mean preoperative serum TF levels in clear cell RCC patients and in controls were 66.8 pg/dL and 28.4 pg/dL, respectively (p<0.001). Mean postoperative serum TF levels in clear cell RCC patients were 26.3 pg/dL. In all patients with clear cell RCC postoperative serum levels of TF were lower, with a mean reduction of 41.6 pg/dL in the postoperative setting (p<0.001). Linear regression revealed that tumor size was correlated with the postoperative reduction of serum TF levels (p=0.037). CONCLUSIONS: We have shown a 3-fold reduction in the median preoperative serum levels of TF in patients with clear cell RCC after surgery. We have also shown a difference of the same magnitude in the serum levels of TF compared with those of a control group of patients with benign diseases. TF appears to be a useful serum marker for the presence of clear cell RCC. Further studies are needed to validate these findings.

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.

Angiotensin Converting Enzyme 90 kDa isoform: Biomarker for diagnosis of preeclampsia?

Preeclampsia (PE), one of the leading gestational hypertensive diseases, is characterized by increased blood pressure (⩾140/90mmHg) and pathological proteinuria after 20weeks gestation. It is a complex, multifactorial syndrome with an unestablished etiology and cure. The search continues for a biomarker that could assist in the early prediction or diagnosis of PE, reducing the rate of maternal and fetal mortality. Based on the findings of Casarini et al. that suggest the 90kDa isoform of the Angiotensin Converting Enzyme (ACE) as a possible marker of hypertension, we hypothesized that this isoform may be present in pregnant women with PE, since they present a transient and spontaneous model of systemic arterial hypertension in pregnancy. We believe, therefore, that pregnant women with pure PE (PPE) express the ACE 90kDa isoform in urine, as well as having elevated isoform enzymatic activity, during pregnancy only. Postpartum, with the normalization of blood pressure, the protein isoform would no longer be expressed. Pregnant women with superimposed preeclampsia (SPE) would present the ACE 90kDa isoform both during and after the gestation period, and its enzymatic activity would remain high as they are chronically hypertensive. It is expected that normotensive pregnant women do not present this isoform in their urine as elevated blood pressure levels do not occur. Both normotensive and PPE affected pregnant women with a family history of hypertension, will possibly express the ACE 90kDa isoform before pregnancy and may become hypertensive, only after some years, through the influence of environmental factors and/or other diseases. If our hypothesis is confirmed, it will allow differentiation of PPE and SPE sooner than 12weeks postpartum, which is currently the estimated period for confirmation of the specific diagnosis. Furthermore, it could be an early biomarker for predicting the disease, enabling the physician to choose the best clinical management. In addition, it would minimize the use of other methods as the biological sample for obtaining the marker is urine, a practical and effective test with good reproducibility. Finally, test results would enable a greater understanding of the mechanisms involved in gestational hypertension.

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.

Erythrocyte L-arginine uptake in peritoneal dialysis patients changes over time.

During long-term exposure to continuous ambulatory peritoneal dialysis (PD), the characteristics of the peritoneal membrane may be altered. The substrate for nitric oxide synthesis is L-arginine, which may enter cells via the y+ and y+L transport systems. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-NO pathway. Maximal capacity for L-arginine transport is higher in patients with a lower dialysis adequacy index. Our aim was to evaluate erythrocyte L-arginine uptake in PD patients at the start and end of a 3-year interval. Our longitudinal study evaluated 8 stable patients on PD who were not using NO donors and who had been free of peritonitis for at least 1 month. Uptake of L-arginine was measured in 2003 and again in 2006. Maximal transport capacity (Vmax, in micromoles per liter-cells per hour) and half-saturation constant (km, in micromoles per liter) were measured in erythrocytes using 14C as a marker and N-ethylmaleimide as inhibitor of the y+ system. For the years 2003 and 2006 respectively, mean +/- standard deviation for total L-arginine uptake Vmax was 749 +/- 182 micromol/L-cells/h and 1146 +/- 365 micromol/L-cells/h (p = 0.016, paired t-test),for y+L Vmax was 180 +/- 58 micromol/L-cells/h and 515 +/- 142 micromol/L-cells/h (p = 0. 002), and for y+ Vmax was 556 +/- 177 micromol/L-cells/h and 662 +/- 267 micromol/ L-cells/h (nonsignificant). The total y+L and y+km were not significantly different. The L-arginine maximal uptake capacity in erythrocytes increased after 3 years of PD treatment. These findings agree with the suggestion of an association between y+L activity and dialysis adequacy or uremia toxicity. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-NO pathway.

Erythrocyte L-arginine uptake in peritoneal dialysis patients: systems y and y+ L.

L-Arginine is the substrate for nitric oxide synthesis and may enter cells by the y+ and y+ L transport systems. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-nitric oxide pathway. In a cross-sectional study, we evaluated erythrocyte L-arginine uptake in stable peritoneal dialysis (PD) patients with various categories of peritoneal transport function. We used 14C as a marker and N-ethyl-maleimide as an inhibitor of the y+ system to measure maximal uptake capacity (Vma in ulmol/L cell/h) and the half-saturation constant (Km in micromol/L) in erythrocytes. The sample consisted of 41 patients (mean age: 50 +/- 17 years; 5 with diabetes; 18 men). Mean dialysate-toplasma creatinine (D/P(Cr)) was 0.62 +/- 0.14. Peritoneal membrane transport was classified as high, high-average, low-average, or low in 10, 11, 11, and 9 patients, respectively. Mean y+ L Vmax, was 208 +/- 111 micromol/L cell/h, 494 +/- 893 micromol/L cell/h, 222 +/- 59 micromol/L cell/h, and 193 +/- 63 umol/L cell/h [p = 0.404, analysis of variance (ANOVA)] for the high, high-average, low-average, and low transporters respectively. Similarly, mean y+ Vmax was 963 +/- 1034 micromol/L cell/h 843 +/- 366 micromol/L cell/h, 639 +/- 254 micromol/L cell/h, and 774 +/- 378 micromol/L cell/h (p = 0.647, ANOVA). As with Vmax, the y+ L Km and y+ Km values were not significantly different between the various peritoneal transport categories. A negative correlation was observed between y+ Vmax and Kt/V (r = -0.393, p = 0.011). Erythrocyte uptake of L-arginine does not vary with peritoneal membrane transport characteristics, but maximal L-arginine uptake capacity is higher in patients with a lower Kt/V.

L-arginine erythrocyte transport increases during pregnancy and immediately postpartum.

OBJECTIVE: This study was undertaken to evaluate erythrocyte membrane transport of L-arginine in pregnancy and immediately postpartum. STUDY DESIGN: The study comprised 103 women with normal pregnancy, initially evaluated at the second trimester (II), followed into the third trimester (III), and immediately postpartum (PP). Total erythrocyte L-arginine uptake was measured with (14)C-L-arginine, at 37 degrees C, for 3 minutes. The maximal transport capacity (V(max)) and half-saturation constant (K(m)) were obtained with the use of Michaelis-Menten kinetics. Results are expressed as mean+/-SD. Analysis of variance, followed by Tukey test, was used in statistical analysis (alpha< or =.05). RESULTS: V(max) (micromol/L cells per hour) progressively increased at each consecutive time period: 779+/-283, 946+/-289, and 1349+/-390, at II, III, and PP, respectively (P<.001). Similarly, K(m) (micromol/L) values increased from 56+/-20 at time II, to 62+/-18 at time III, and 69+/-24 at PP (P<.001). CONCLUSION: Total erythrocyte L-arginine uptake (V(max) and K(m)) increases progressively along normal pregnancy, with a further increase immediately postpartum.