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T6.3 Preeclamptic organ disorders correlate with diastolic high blood pressure, and preeclamptic CNS disorders with systolic high blood pressure
State of the Art Lectures, Plenary Presentations and Oral Communications / Pregnancy Hypertension 1, Supplement 1 (2010) S1–S41
T6.2
T6.4
Phenotypic characterization of kidney podocytes from women with preeclampsia
Plasma 25-hydroxyvitamin D in early-onset severe preeclampsia
Shuang Zhao, Yang Gu, Gregory Coates, Xin Gu, Lynn J. Groome, Yuping Wang. LSUHSC-Shreveport, LA, USA Objective: Recent study suggests that podocyturia might be a sensitive indicator to evaluate kidney injury in preeclampsia (PE). However, little information is available as to the mechanism underlying kidney podocyte shedding in PE. This study was undertaken to characterize phenotypic changes in podocytes from women with PE. Methods: Podocytes were extracted and cultured from urinary samples from women with normal (n=6) and PE (n=14) pregnancies. We examined: 1) specific podocyte proteins nephrin and podoplanin; 2) polarity proteins PARD-3 and PARD-6; 3) angiotensin II receptor AT-1 and AT2; 4) VEGF and its receptor Flt-1; and 5) filament linker protein Ezrin expressions by immunofluorescent staining of podocytes in culture. Podocytes were also examined by transmission electron microscopy. Podocyte cell line was used as control. Results: No podocyte was found in urinary samples from normal pregnant women, whereas podocytes were positive in more than 80% urinary samples from PE. In control podocytes (cell line), nephrin, PARD-3, PARD-6, AT-2, VEGF, Flt-1, and Ezrin expressions were localized in peripheral regions and around cell borders, but expressions of these proteins were reduced or lost in the peripheral region in podocytes from PE. Lack of podocyte foot processes was confirmed by electron microscopic examination in podocytes from PE compared to control podocytes. Podoplanin was expressed in podocyte surface in control cells, but its expression was reduced in podocytes from PE. Conclusions: Nephrin is a marker for podocyte foot processes. Loss of slit protein nephrin and polarity protein PARD-3 and PARD-6 in foot processes could explain podocyte detachment from glomerular basement membrane and result in podocyte shedding in PE. Reduced AT2, VEGF, Flt-1 and Ezrin expressions in foot processes could be a consequence of podocyte dysfunction in PE. These data demonstrate that glomerular podocytes undergo significant phenotypic changes in PE.
T6.3 Preeclamptic organ disorders correlate with diastolic high blood pressure, and preeclamptic CNS disorders with systolic high blood pressure Osamu Nakamoto, Reiko Tasaka, Ikuko Mita, Itsuko Okuda, Tomoko Sumikura, Chika Motohisa, Shigeki Matsuo. Department of Obstetrics, Osaka City General Hospital, Japan Purpose: Preeclampsia especially with severe hypertension accompanied with severe proteinuria (HP) might have the highest potency of maternal organ damages. We studied the levels of hypertension or proteinuria in cases of preeclampsia or predicting maternal obstetric disorders. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were considered as independent parameters each other in this study. Statistical analysis was performed how obstetric confounding parameters such as sBP, dBP, daily amount of proteinuria (ProU), week of onset of disease and so on, were to be correlated with obstetric disorders by logistic regression analysis (LRA). CNS disorders such as eclampsia or cortical blindness, and other organ disorders such as renal failure or HELLP syndrome were subclassified. Statistical analysis was performed in each disorders and total disorders. Method: 108 cases of preeclampsia with HP onset newly after 20 weeks were entered. Cases below 34 weeks were managed expectantly under hospitalization until progression of maternal or fetal malfunctions. Univaiate and multivariate LRA were done by peak sBP, peak dBP or peak ProU in the antepartum as covaiates, and each disorders as dependent variable. Result: Total disorders were the most correlated with dBP≥110mmg (adjusted Odds ratio [aOR]=3.52, p=0.025) and ProU≥5g/day (aOR=4.48, p=0.033). Organ disorders also had the same results. CNS disorders had the most significant correlation with sBP (aOR=5.43, p=0.018). Discussion: We showed severe dBP≥110mmHg affected mostly to total obstetric disorders, especially organ disorders in preeclampsia with HP. Severe dBP would cause the pregnant condition to accelerate vascular endothelial damage resulting in organ disorders such as HELLP syndrome. CNS disorders had the strongest correlation with severe sBP≥200mmHg. CNS disorders, different from organ disorders, might be affected by systolic high pressure. In cases of once severely progressed preeclampsia, diastolic high BP is regarded as organ disorders risk, and systolic high BP as CNS disorders risk.
S17
Christopher Robinson, Mark Alanis, Carol Wagner, Bruce Hollis, Donna Johnson. Medical University of South Carolina, USA Objective: Vitamin D is a potent sterol hormone involved in a diverse array of biological processes through regulation of over 900 gene products. Vitamin D deficiency has been suggested to be linked to adverse pregnancy outcomes through effects on placental development, angiogenesis, and immune function. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-(OH)D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). Study design: Following IRB approval, this case-control investigation enrolled subjects with EOSPE (< 34 weeks gestation with severe preeclampsia) in a 1:2 ratio with healthy, contemporaneous controls matched for gestational age at case diagnosis. Demographic and outcome information was collected for each subject. Plasma was collected and stored at -70°C until analysis. Total 25-(OH)D levels were determined by radioimmunoassay and reported in ng/mL. Results were analyzed with Wilcoxon rank sum test. Regression modeling was used to control for potential confounders. Results: 50 subjects with EOSPE and 100 healthy controls were included. Gestational age at inclusion, nulliparity, maternal age, and maternal race were similar between groups. Subjects with EOSPE had increased body mass index relative to control (p=0.02). Subjects with EOSPE were noted to have decreased total 25-(OH)D levels relative to healthy controls (p<0.001). This difference in total 25-(OH)D remained significant after controlling for potential confounders. Conclusion: Total 25-(OH)D is depressed in subjects affected with EOSPE at the time of diagnosis. Further study is necessary to fully understand the impact of vitamin D deficiency on pregnancy outcomes. Recognizing that Vitamin D deficiency is common and correctable with sun exposure and dietary modification, clinical trials of replacement are necessary to evaluate the possible impact of supplementation on adverse pregnancy outcomes.
T7.1 A comparison of different methodologies in flow mediated dilatation in women with pre-eclampsia compared to women with gestational hypertension Ann Quinton, Michael Peek, Colleen-M. Cook, Adrienne Kirby. University of Sydney, Australia Objectives: To assess flow-mediated dilatation (FMD) in women with preeclampsia (PE) versus gestational hypertension (GH) and determine if newer FMD techniques vary the results. Methods: Hypertensive (BP ≥140/90mmHg) pregnant women were recruited. If proteinuria ≥300mg/24 hours was present, women were allocated to the PE group. Percentage FMDo was calculated from the difference in baseline and post-occlusion diameter at 45-60s. FMDmax used baseline and maximum diameter between 45-90s, adjusted for haematocrit and shear rate. Results: FMDo (m ± SD) was comparable (P=0.4) in the no medication GH (5.3±3.2; n=15) and PE (6.5±4.1; n=13) groups. FMDo was reduced (P<0.001) in the medication GH (3.7±2.8; n=23) versus PE (8.8±4.3; n=25) groups. The interaction between group and medication for FMDmax was not significant (both P=0.08) in unadjusted analysis or analysis adjusted for covariates haematocrit (P=0.023) and shear rate (P=0.007) so means averaged over medication are presented. FMDmax was reduced (P<0.0001) in the GH (5.7±3.5; n=38) versus PE group (9.2±4.0; n=38). Seventy nine percent (30/38) of the PE women reached maximum dilatation by 90s compared to 63% (24/38) of GH women (Chi-square, P=0.16). Conclusions: A final consensus of the FMD technique has not been reached. Results differed depending on the methodology used. No difference in FMDo was demonstrated between the GH and PE groups on no medication. A difference when comparing PE and GH women was demonstrated when FMDmax analysis was used. This difference in the two analyses may be due to the GH women having a longer time to peak maximum dilation. We hypothesise that PE and GH may be differing diseases.
T6.2
T6.4
Phenotypic characterization of kidney podocytes from women with preeclampsia
Plasma 25-hydroxyvitamin D in early-onset severe preeclampsia
Shuang Zhao, Yang Gu, Gregory Coates, Xin Gu, Lynn J. Groome, Yuping Wang. LSUHSC-Shreveport, LA, USA Objective: Recent study suggests that podocyturia might be a sensitive indicator to evaluate kidney injury in preeclampsia (PE). However, little information is available as to the mechanism underlying kidney podocyte shedding in PE. This study was undertaken to characterize phenotypic changes in podocytes from women with PE. Methods: Podocytes were extracted and cultured from urinary samples from women with normal (n=6) and PE (n=14) pregnancies. We examined: 1) specific podocyte proteins nephrin and podoplanin; 2) polarity proteins PARD-3 and PARD-6; 3) angiotensin II receptor AT-1 and AT2; 4) VEGF and its receptor Flt-1; and 5) filament linker protein Ezrin expressions by immunofluorescent staining of podocytes in culture. Podocytes were also examined by transmission electron microscopy. Podocyte cell line was used as control. Results: No podocyte was found in urinary samples from normal pregnant women, whereas podocytes were positive in more than 80% urinary samples from PE. In control podocytes (cell line), nephrin, PARD-3, PARD-6, AT-2, VEGF, Flt-1, and Ezrin expressions were localized in peripheral regions and around cell borders, but expressions of these proteins were reduced or lost in the peripheral region in podocytes from PE. Lack of podocyte foot processes was confirmed by electron microscopic examination in podocytes from PE compared to control podocytes. Podoplanin was expressed in podocyte surface in control cells, but its expression was reduced in podocytes from PE. Conclusions: Nephrin is a marker for podocyte foot processes. Loss of slit protein nephrin and polarity protein PARD-3 and PARD-6 in foot processes could explain podocyte detachment from glomerular basement membrane and result in podocyte shedding in PE. Reduced AT2, VEGF, Flt-1 and Ezrin expressions in foot processes could be a consequence of podocyte dysfunction in PE. These data demonstrate that glomerular podocytes undergo significant phenotypic changes in PE.
T6.3 Preeclamptic organ disorders correlate with diastolic high blood pressure, and preeclamptic CNS disorders with systolic high blood pressure Osamu Nakamoto, Reiko Tasaka, Ikuko Mita, Itsuko Okuda, Tomoko Sumikura, Chika Motohisa, Shigeki Matsuo. Department of Obstetrics, Osaka City General Hospital, Japan Purpose: Preeclampsia especially with severe hypertension accompanied with severe proteinuria (HP) might have the highest potency of maternal organ damages. We studied the levels of hypertension or proteinuria in cases of preeclampsia or predicting maternal obstetric disorders. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were considered as independent parameters each other in this study. Statistical analysis was performed how obstetric confounding parameters such as sBP, dBP, daily amount of proteinuria (ProU), week of onset of disease and so on, were to be correlated with obstetric disorders by logistic regression analysis (LRA). CNS disorders such as eclampsia or cortical blindness, and other organ disorders such as renal failure or HELLP syndrome were subclassified. Statistical analysis was performed in each disorders and total disorders. Method: 108 cases of preeclampsia with HP onset newly after 20 weeks were entered. Cases below 34 weeks were managed expectantly under hospitalization until progression of maternal or fetal malfunctions. Univaiate and multivariate LRA were done by peak sBP, peak dBP or peak ProU in the antepartum as covaiates, and each disorders as dependent variable. Result: Total disorders were the most correlated with dBP≥110mmg (adjusted Odds ratio [aOR]=3.52, p=0.025) and ProU≥5g/day (aOR=4.48, p=0.033). Organ disorders also had the same results. CNS disorders had the most significant correlation with sBP (aOR=5.43, p=0.018). Discussion: We showed severe dBP≥110mmHg affected mostly to total obstetric disorders, especially organ disorders in preeclampsia with HP. Severe dBP would cause the pregnant condition to accelerate vascular endothelial damage resulting in organ disorders such as HELLP syndrome. CNS disorders had the strongest correlation with severe sBP≥200mmHg. CNS disorders, different from organ disorders, might be affected by systolic high pressure. In cases of once severely progressed preeclampsia, diastolic high BP is regarded as organ disorders risk, and systolic high BP as CNS disorders risk.
S17
Christopher Robinson, Mark Alanis, Carol Wagner, Bruce Hollis, Donna Johnson. Medical University of South Carolina, USA Objective: Vitamin D is a potent sterol hormone involved in a diverse array of biological processes through regulation of over 900 gene products. Vitamin D deficiency has been suggested to be linked to adverse pregnancy outcomes through effects on placental development, angiogenesis, and immune function. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-(OH)D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). Study design: Following IRB approval, this case-control investigation enrolled subjects with EOSPE (< 34 weeks gestation with severe preeclampsia) in a 1:2 ratio with healthy, contemporaneous controls matched for gestational age at case diagnosis. Demographic and outcome information was collected for each subject. Plasma was collected and stored at -70°C until analysis. Total 25-(OH)D levels were determined by radioimmunoassay and reported in ng/mL. Results were analyzed with Wilcoxon rank sum test. Regression modeling was used to control for potential confounders. Results: 50 subjects with EOSPE and 100 healthy controls were included. Gestational age at inclusion, nulliparity, maternal age, and maternal race were similar between groups. Subjects with EOSPE had increased body mass index relative to control (p=0.02). Subjects with EOSPE were noted to have decreased total 25-(OH)D levels relative to healthy controls (p<0.001). This difference in total 25-(OH)D remained significant after controlling for potential confounders. Conclusion: Total 25-(OH)D is depressed in subjects affected with EOSPE at the time of diagnosis. Further study is necessary to fully understand the impact of vitamin D deficiency on pregnancy outcomes. Recognizing that Vitamin D deficiency is common and correctable with sun exposure and dietary modification, clinical trials of replacement are necessary to evaluate the possible impact of supplementation on adverse pregnancy outcomes.
T7.1 A comparison of different methodologies in flow mediated dilatation in women with pre-eclampsia compared to women with gestational hypertension Ann Quinton, Michael Peek, Colleen-M. Cook, Adrienne Kirby. University of Sydney, Australia Objectives: To assess flow-mediated dilatation (FMD) in women with preeclampsia (PE) versus gestational hypertension (GH) and determine if newer FMD techniques vary the results. Methods: Hypertensive (BP ≥140/90mmHg) pregnant women were recruited. If proteinuria ≥300mg/24 hours was present, women were allocated to the PE group. Percentage FMDo was calculated from the difference in baseline and post-occlusion diameter at 45-60s. FMDmax used baseline and maximum diameter between 45-90s, adjusted for haematocrit and shear rate. Results: FMDo (m ± SD) was comparable (P=0.4) in the no medication GH (5.3±3.2; n=15) and PE (6.5±4.1; n=13) groups. FMDo was reduced (P<0.001) in the medication GH (3.7±2.8; n=23) versus PE (8.8±4.3; n=25) groups. The interaction between group and medication for FMDmax was not significant (both P=0.08) in unadjusted analysis or analysis adjusted for covariates haematocrit (P=0.023) and shear rate (P=0.007) so means averaged over medication are presented. FMDmax was reduced (P<0.0001) in the GH (5.7±3.5; n=38) versus PE group (9.2±4.0; n=38). Seventy nine percent (30/38) of the PE women reached maximum dilatation by 90s compared to 63% (24/38) of GH women (Chi-square, P=0.16). Conclusions: A final consensus of the FMD technique has not been reached. Results differed depending on the methodology used. No difference in FMDo was demonstrated between the GH and PE groups on no medication. A difference when comparing PE and GH women was demonstrated when FMDmax analysis was used. This difference in the two analyses may be due to the GH women having a longer time to peak maximum dilation. We hypothesise that PE and GH may be differing diseases.