Decreased Ang-(1-7) and Downregulated Intrarenal RAS May Contribute to the Direct Podocyte Injury With Proteinuria in Preeclampsia.

The mechanisms of proteinuria development in preeclampsia (PE) are still enigmatic. Renin-angiotensin system (RAS) components may play a role. Maternal serum and urinary concentrations of angiotensin-(1-7) [Ang-(1-7)], angiotensin II (Ang II), and angiotensinogen in women with PE (n = 14), gestational hypertension (n = 14), and normal pregnancy were quantified. The alteration in these concentrations was used to evaluate their relationships with podocyturia and proteinuria in PE. In addition, the podocytes cultured in vitro were interfered in serum of preeclamptic and normotensive pregnant women, with or without Ang-(1-7). The morphologic change in podocyte was observed using a microscope. The changes in podocyte-specific proteins (nephrin, CD2-associated protein [CD2AP]), the cytoskeletal protein F-actin, the tight junction protein (ZO-1), and Mas receptor (MasR) were examined by immunofluorescence. Western blot was used to examine the expression and variation of MasR. We found that the concentrations of RAS components were associated with prepartal urinary podocyte number, random urine albumin/creatinine ratio, blood pressure, and renal function. The expression of nephrin, F-actin, ZO-1, and MasR on podocytes interfered in serum of PE was significantly decreased compared to normal control and normal pregnant serum group in vitro, yet their expression was significantly increased after coculture by 10-6 mol/L Ang-(1-7) and the preeclamptic serum. The expression of CD2AP had no significant difference. We concluded that decreased Ang-(1-7) and downregulated intrarenal RAS contributed to the direct podocyte injury with proteinuria in PE.

Early pregnancy bisphenol and phthalate metabolite levels, maternal hemodynamics and gestational hypertensive disorders.

STUDY QUESTION: Are early-pregnancy urinary bisphenol and phthalate metabolite concentrations associated with placental function markers, blood pressure (BP) trajectories during pregnancy and risk of gestational hypertensive disorders? SUMMARY ANSWER: Early-pregnancy bisphenols and phthalate metabolites were not consistently associated with maternal BP changes or gestational hypertensive disorders, but subclinical, statistically significant associations with placental angiogenic markers and placental hemodynamics were identified. WHAT IS KNOWN ALREADY: In vitro studies suggest that bisphenols and phthalate metabolites may disrupt early placental development and affect the risk of gestational hypertensive disorders. Previous studies investigating effects of bisphenols and phthalate metabolites on gestational hypertensive disorders reported inconsistent results and did not examine placental function or BP throughout pregnancy. STUDY DESIGN, SIZE, DURATION: In a population-based prospective cohort study, bisphenol and phthalate metabolite concentrations were measured in a spot urine sample in early pregnancy among 1396 women whose children participated in postnatal follow-up measurements. PARTICIPANTS/MATERIALS, SETTING, METHODS: After exclusion of women without any BP measurement or with pre-existing hypertension, 1233 women were included in the analysis. Urinary bisphenol and phthalate metabolite concentrations were measured in early-pregnancy [median gestational age 13.1 weeks, inter-quartile range 12.1-14.5]. Molar sums of total bisphenols and of low molecular weight phthalate, high molecular weight (HMW) phthalate, di-2-ethylhexylphthalate, and di-n-octylphthalate metabolites were calculated. Placental angiogenic markers (placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt)-1), placental hemodynamic function measures (umbilical artery pulsatility index (PI), uterine artery resistance index (RI), notching and placental weight), and maternal BP were measured in different trimesters. Information on gestational hypertensive disorders was obtained from medical records. MAIN RESULTS AND THE ROLE OF CHANCE: Each log unit increase in HMW phthalate metabolites was associated with a 141.72 (95% CI: 29.13, 373.21) higher early pregnancy sFlt-1/PlGF ratio (range in total sample 9-900). This association was driven by mono-[(2-carboxymethyl)hexyl]phthalate. In the repeated measurements regression models, each log unit increase in bisphenol A was associated with a 0.15 SD (95% CI: 0.03, 0.26) higher intercept and -0.01 SD (95% CI: -0.01, -0.00) decreasing slope of the umbilical artery PI Z-score and a -1.28 SD (95% CI: -2.24, -0.33) lower intercept and 0.06 SD (95% CI: 0.02, 0.11) increasing slope of the uterine artery RI Z-score. These associations remained significant after Bonferroni correction. Early-pregnancy bisphenols or phthalate metabolites showed no consistent associations with any other outcome. LIMITATIONS, REASONS FOR CAUTION: Information on a large number of potential confounders was available but was partly self-reported. Bisphenols and phthalate metabolites, which typically have a half-life of 24-48 h, were measured via single spot urine samples in early-pregnancy. In addition, at the current sample size, the study was powered to detect an odds ratio of 1.57 for gestational hypertension and 1.78 for pre-eclampsia, but was underpowered to perform multivariable analyses for these outcomes. Further studies combining data from different cohorts may be necessary to increase power. These limitations are possible sources of non-differential misclassification leading to bias toward the null. WIDER IMPLICATIONS OF THE FINDINGS: Bisphenols and phthalate metabolites were not associated with longitudinal changes in BP in pregnancy in our low-risk population. The observed subclinical associations of phthalates with the sFlt-1/PlGF ratio and of bisphenol A with placental hemodynamics may contribute to adverse pregnancy outcomes. Our results are therefore more supportive of an association of early pregnancy bisphenols and phthalate metabolites with risk for pre-eclampsia than with gestational hypertension. STUDY FUNDING/COMPETING INTEREST(S): This analysis was supported by Grant (ES022972) from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors report no conflicts of interest.

[Features of the urine peptidome under the condition of hypertensive pathologies of pregnancy]. / Osobennosti peptidoma mochi pri gipertenzivnykh patologiiakh beremennykh.

In order to find a peptide panel to differentiate close hypertensive conditions a case-control study was designed for 64 women from 4 groups: preeclampsia (PE), chronic hypertension superimposed with PE, chronic hypertension, and healthy individuals. Chromatography coupled with mass-spectrometry and subsequent bioinformatic analysis showed several patterns in the changes of the urine peptidome. There were 36 peptides common for four groups. Twenty two of them 22 belonged to alpha-1-chain of collagen I, nine peptides were from alpha-1-chain of collagen III, two from alpha-2-chain of collagen I, one from alpha-1/2-chain of collagen I, one from alpha-1-chain of collagen I/XVIII and one from uromodulin. Patients with hypertensive disorders had 34 common peptides: 12 from alpha-1-chain of collagen I, 10 from fibrinogen alpha-chain, eight from alpha-1-chain of collagen III, and 4 per other types of collagen. Comparative analysis revealed 12 peptides, which could be used as a diagnostic panel for confident discrimination of pregnant women with various hypertensive disorders.

Alto rendimiento clínico entre albuminuria semicuantitativa y proteinuria de 24 horas en pacientes con sospecha de síndrome hipertensivo del embarazo / High clinical performance between semiquantitative albuminuria and 24-hour proteinuria in patients with suspected hypertensive syndrome of pregnancy

ANTECEDENTES: La evaluación precisa de la proteinuria constituye un pilar importante para el diagnóstico del síndrome hipertensivo del embarazo (SHE). El estándar dorado para esta medición es la recolección de orina en 24 horas, pero debido a la duración de la toma de la muestra, alternativas como la albuminuria semicuantitativa se utiliza con mayor frecuencia en los servicios de urgencia de nuestro país. OBJETIVO: Evaluar el rendimiento diagnóstico de la albuminuria semicuantitativa y su asociación con proteinuria de 24 horas en pacientes con SHE. MÉTODOS: Estudio retrospectivo de 145 pacientes con sospecha de SHE atendidas en el Hospital Padre Hurtado, Chile. A todas las pacientes se le realizó albuminuria semicuantitativa (categorizada entre 0+ y 4+) y proteinuria de 24 horas (positivo si >0,3 gramos/24 horas). Se realizó análisis por grupos compuestos de albuminuria semicuantitativa y resultado positivo en proteinuria de 24 horas. RESULTADOS: Se evidenció una sensibilidad de 50%, especificidad de 100%, VPP de 100%, VPN de 65,7%, LR+ de 50 y un LR- de 0,5. CONCLUSIÓN: La albuminuria semicuantitativa ≥2+ muestra una fuerte asociación con proteinuria ≥0,3 g/24 horas y es un método rápido para evaluar SHE.

BACKGROUND: One of the basis for the diagnosis of pregnancy induced hypertension syndrome (PIHS), includes the precise evaluation of proteinuria. The gold standard for its evaluation is the collection of a 24-hour urine specimen, but because it is a slow method, other alternatives, such as semi-quantitative albuminuria have been used more frequently on our emergency rooms. OBJECTIVE: To assess the diagnostic performance of semi-quantitative albuminuria and its association with proteinuria measured in a 24-hour urine specimen collection, in patients with PIHS. METHODS: Retrospective study of 145 patients with clinical suspicion of PIHS who assisted to Hospital Padre Hurtado, Chile. Semi-quantitative albuminuria (categorized as 0 to 4+) and proteinuria measured in a 24-hour urine specimen collection was measured on every patient. Abnormal values of proteinuria were considered when values exceeded 0.3 g/24 hours. Composite outcomes analysis was done between albuminuria groups and positive proteinuria in 24 hrs. RESULTS: Sensibility and specificity of semi-quantitative albuminuria was of 50% and 100%, respectively, with a PPV: 100%, NPV: 65.7%, LR+: 50 and a LR-: 0.5. CONCLUSION: semi-quantitative albuminuria ≥2+ shows a strong association with proteinuria ≥0.3 g/24 hours and it could be used as a fast method to assess PIHS.

Prevalence of asymptomatic bacteriuria and its consequences in pregnancy in a rural community of Bangladesh.

This was a cross-sectional followed by cohort type of study conducted among the pregnant mothers of second trimester in the rural areas of Rajshahi district. Initially 1800 pregnant mothers ofsecond trimester were selected from 18 unions applying 2-stage random sampling. A total of 216 pregnant mothers with asymptomatic bacteriuria were paired among the rest of the healthy pregnant mothers (without bacteriuria) on the basis of age, gravida and economic status for cohort study to relate asymptomatic bacteriuria with the incidence of symptomatic bacteriuria, hypertensive disorders in pregnancy (HDP) and pre-term delivery. The matched paired pregnant mothers werefollowed monthly interval up to delivery. The prevalence of asymptomatic bacteriuria was 12% among the pregnant mothers in rural Rajshahi. E. Coli was the commonest causative agent of both asymptomatic and symptomatic bacteriuria. The results of this study suggest that asymptomatic bacteriuria were more prone to develop symptomatic bacteriuria, hypertensive disorders in pregnancy and pre-term delivery than that of the healthy mothers (without bacteriuria). Screening of bacteriuria in pregnancy and proper treatment must be considered as an essential part of antenatal care in this rural community.

Twenty-four-hour urine insulin as a measure of hyperinsulinaemia/insulin resistance before onset of pre-eclampsia and gestational hypertension.

OBJECTIVE: To evaluate levels of 24-hour urine insulin excretion before the onset of pre-eclampsia and gestational hypertension. DESIGN: Nested case-control study within the Calcium for Preeclampsia Prevention (CPEP) study cohort. SETTING: Five university medical centres in the United States. SAMPLE: Cases had developed pre-eclampsia (n= 70) or gestational hypertension (n= 142) in the absence of gestational diabetes. Controls (n= 429) had remained normotensive without gestational diabetes. METHODS: Subjects were required to have had an adequate baseline 24-hour urine collection prior to CPEP enrolment at 13-21 weeks. Controls were matched to cases by enrolment site and specimen storage time, without regard to gestational age or CPEP treatment. Adjusted mean 24-hour urine insulin excretion was, however, calculated using analysis of covariance, with adjustment models for pre-eclampsia considering body mass index, race and smoking status; and for gestational hypertension, gestational age at specimen collection, height, body mass index and smoking. Urine insulin was measured by radio-immunoassay. MAIN OUTCOME MEASURES: Twenty-four-hour urine insulin excretion. RESULTS: Adjusted 24-hour urine insulin excretion at baseline (mean 17 weeks of gestation) was greater in women who developed pre-eclampsia than in normotensive controls (mean [SE]: 15.6 [1.5] vs 13.1 [1.2] x 10(3)microIU/24 hour, P= 0.06), but not in women who developed gestational hypertension (14.7 [0.9] vs 15.0 [0.6] x 10(3)microIU/24 hour, P= 0.79, in cases vs controls). Among women who developed pre-eclampsia, adjusted urine insulin excretion was greater than controls only in women with mild pre-eclampsia and not in severe pre-eclampsia (mild pre-eclampsia vs controls: 17.3 [2.0] vs 13.7 [1.6] x 10(3)microIU/24 hour, P= 0.04; severe pre-eclampsia vs controls: 12.3 [2.2] vs 11.5 [1.2], P= 0.69). CONCLUSION: The data suggest that early hyperinsulinaemia, a marker of insulin resistance, may predispose to mild pre-eclampsia.