Uric Acid as a Pathogenic Factor in Preeclampsia

Lab 336A, Magee-Womens Research Institute, 204 Craft Ave, Pittsburgh, PA 15213, USA.
Placenta (Impact Factor: 2.71). 04/2008; 29 Suppl A(suppl A):S67-72. DOI: 10.1016/j.placenta.2007.11.001
Source: PubMed


Hyperuricemia is a common finding in preeclamptic pregnancies evident from early pregnancy. Despite the fact that elevated uric acid often pre-dates the onset of clinical manifestations of preeclampsia, hyperuricemia is usually considered secondary to altered kidney function. Increased serum uric acid is associated with hypertension, renal disease and adverse cardiovascular events in the non-pregnant population and with adverse fetal outcomes in hypertensive pregnancies. We hypothesize that an elevated concentration of uric acid in preeclamptic women is not simply a marker of disease severity but rather contributes directly to the pathogenesis of the disorder. Using epidemiological and experimental evidence, gained largely outside of pregnancy, we will propose pathogenic roles for uric acid in preeclamptic pregnancies. Uric acid's ability to promote inflammation, oxidative stress and endothelial dysfunction will be highlighted with discussions of the potential impact on placental development and function and maternal vascular health.

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Available from: James M Roberts, Mar 14, 2014
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    • "Our results regarding the significant association between maternal, umbilical and neonatal serum uric acid levels, supported by studies that demonstrate the free transfer of uric acid through the placenta [6], suggest that the real etiology for these poor neonatal outcomes might be the elevated uric acid in maternal sera; neonatal hyperuricemia may be only a reflection of maternal and umbilical hyperuricemia. This vicious effect of uric acid might be due to the prooxidative effect of uric acid and its ability to promote inflammation and endothelial dysfunction [25,26]. "
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    ABSTRACT: To assess the association of maternal hyperuricemia with adverse pregnancy outcome and neonatal metabolic, neurologic and respiratory disturbances in normotensive singleton pregnant women. This prospective multicentric cohort study was conducted on 404 normotensive singleton pregnant women who were admitted for delivery in Vali-Asr and Akbar-Abadi teaching hospitals of Tehran University of Medical Sciences, Tehran, Iran. Upon enrollment maternal and umbilical sera were obtained for determining uric acid levels. 1 and 5 minutes Apgar scores, the need for neonatal resuscitation and neonatal intensive care unit (NICU) admission were recorded. In case of NICU admission a neonatal blood sample was drawn for determining uric acid, blood sugar and bilirubin levels. An intracranial ultrasound imaging was also carried out for the admittd neonates for detecting intraventricular hemorrhage. Maternal hyperuricemia (uric acid one standard deviation greater than the appropriate gestational age) was independently associated with preterm birth (odds ratio (OR), 3.17; 95% confidence interval (CI), 2.1 - 4.79), small for gestational age delivery (OR, 1.28; 95% CI, 1.04 - 2.57), NICU admission (OR, 1.65; 95% CI, 1.12 - 2.94) and neonatal IVH (OR, 8.14; 95% CI, 1.11 - 87.1). Maternal hyperuricemia in normotensive singleton pregnant women is significantly associated with preterm and SGA delivery and the development of neonatal IVH.
    Full-text · Article · Mar 2014 · BMC Pregnancy and Childbirth
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    • "However, low UA levels in plasma and urine associate with worse cognitive performance in PD [11]. UA is a pathogenic factor in pre-eclampsia for pregnant women [12] [13]. It acts as a role of insulin resistance in older [14] and pregnant women [15]. "
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    ABSTRACT: This paper describes the sensitive and selective determination of uric acid (UA) in the presence of important interferences, ascorbic acid (AA), dopamine (DA), tyrosine (Tyr) and methionine (Met) at physiological pH using an electropolymerized film of 3-amino-5-mercapto-1,2,4-triazole on glassy carbon (p-AMTa) electrode. The p-AMTa electrode shows an excellent electrocatalytic activity towards UA. This was understood from the observed higher oxidation current and heterogeneous rate constant (3.24×10(-5)ms(-1)) for UA when compared to bare GC electrode (4.63×10(-6)ms(-1)). The selective determination of UA in the presence of 1000-fold excess of AA was achieved using p-AMTa electrode. Further, the p-AMTa electrode was successfully used for the simultaneous and selective determination of UA in the presence of important interferences, DA, Tyr and Met. Using amperometric method, 40nM UA was detected for the first time. The current response of UA was increased linearly while increasing its concentration from 40nM to 0.1mM and a detection limit was found to be 0.52nM (S/N=3). Finally, the practical application of the present method was demonstrated by determining UA in human urine and blood serum samples.
    Full-text · Article · May 2012 · Bioelectrochemistry (Amsterdam, Netherlands)
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    • "Higher levels of uric acid are a common characteristic of PE patients and may contribute to the pathogenesis of the disorder [53]. Antioxidant properties have been also attributed to uric acid [54]. "
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    ABSTRACT: Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation.
    Full-text · Article · May 2012 · Journal of pregnancy
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