Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery

Powers, Robert W.; Bodnar, Lisa M.; Ness, Roberta B.; Cooper, Katheryn M.; Gallaher, Marcia J.; Frank, Michael P.; Daftary, Ashi; Roberts, James M.

doi:10.1016/j.ajog.2005.06.066

Cited by 139 publications

(130 citation statements)

References 22 publications

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“…By term concentrations slowly rise to those observed in non-pregnant women. In contrast to that, uric acid levels increase at 10 wk of gestation and continue to rise until 48 h postpartum in preeclamptic women [90] . The increase in uric acid precedes the reduction in plasma volume in preeclampsia [91] .…”

Section: Uric Acidmentioning

confidence: 81%

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

Müller-Deile

Schiffer

2014

WJN

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Proteinuria is a frequently detected symptom, found in 20% of pregnancies. A common reason for proteinuria in pregnancy is preeclampsia. To diagnose preeclampsia clinically and to get new insights into the pathophysiology of the disease it is at first essential to be familiar with conditions in normal pregnancy. Animal models and biomarkers can help to learn more about disease conditions and to find new treatment strategies. In this article we review the changes in kidney function during normal pregnancy and the differential diagnosis of proteinuria in pregnancy. We summarize different pathophysiological theories of preeclampsia with a special focus on the renal facets of the disease. We describe the current animal models and give a broad overview of different biomarkers that were reported to predict preeclampsia or have a prognostic value in preeclampsia cases. We end with a summary of treatment options for preeclampsia related symptoms including the use of plasmapheresis as a rescue therapy for so far refractory preeclampsia. Most of these novel biomarkers for preeclampsia are not yet implemented in clinical use. Therefore, we recommend using proteinuria (measured by UPC ratio) as a screening parameter for preeclampsia. Delivery is the only curative treatment for preeclampsia. In early preeclampsia the primary therapy goal is to prolong pregnancy until a state were the child has an acceptable chance of survival after delivery.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Preeclampsia; Pregnancy; Proteinuria; Biomarkers; Treatment Core tip: This review summarises different pathophysiological theories of preeclampsia with a special focus on the renal facets of the disease. In this context current animal models are presented. The reader gets a broad overview about different biomarkers for preeclampsia. Furthermore, the article discusses treatment options for preeclampsia related symptoms including the use of plasmapheresis as a rescue therapy for so far refractory preeclampsia.Müller-Deile J, Schiffer M. Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy. World

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Section: Uric Acidmentioning

confidence: 81%

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

Müller-Deile

Schiffer

2014

WJN

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“…32 Insulin resistance 33,34 and uric acid, other components of the metabolic syndrome, are also increased in preeclampsia. 22 Many of these changes, including elevated free fatty acids 35 and uric acid, 36 can be demonstrated from very early pregnancy. Whether they antedate pregnancy has not been established.…”

Section: Pathological and Pathophysiological Changesmentioning

confidence: 99%

Preeclampsia

2005

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Abstract-Preeclampsia is a pregnancy complication with serious consequences for mother and infant. The disorder is diagnosed by gestational hypertension and proteinuria but is far more than pregnancy induced hypertension. Preeclampsia is proposed to occur in 2 stages. Key Words: preeclampsia Ⅲ hypertension, pregnancy Ⅲ oxidative stress Ⅲ endothelium P reeclampsia is a pregnancy complication recognized by new-onset gestational hypertension and proteinuria (see definitions below). The disorder affects both mothers and their infants. Once the disease is evident clinically, it can be cured only by delivery. In developed countries, surveillance for preeclampsia through prenatal care allows for early identification and intervention via delivery. This management has changed little in the last 100 years, and it is very effective at reducing maternal mortality. However, maternal morbidity remains great with preeclampsia, which continues to be one of the leading causes for the admission of pregnant women to intensive care units in the developed world. 1 Furthermore, fetal mortality and morbidity is considerable, related to the effects of the disease on the fetus as well as prematurity. The indicated delivery of women to prevent the progression of preeclampsia is responsible for 15% of all preterm births. 2 In developing countries, where inadequate prenatal care limits preeclampsia surveillance, maternal mortality is common, accounting for 50 000 deaths yearly. 3 The hypertensive disorders of pregnancy include hypertension that antedates pregnancy, chronic hypertension, and gestational hypertension occurring uniquely during pregnancy. When the gestational hypertension is accompanied by new-onset proteinuria, the disorder is termed preeclampsia, and when not associated with proteinuria, transient hypertension of pregnancy. If the woman with chronic hypertension also manifests evidence of preeclampsia, this is classified chronic hypertension with superimposed preeclampsia. Eclampsia is the occurrence of seizures in women with preeclampsia. 4 These criteria have been extraordinarily useful to aid in recognizing pregnant women at risk. Greatest risk for mother and baby is present with preeclampsia, and the risk for chronic hypertensive pregnancy is primarily with superimposed preeclampsia. However, the attention to hypertension has, for many years, limited research attention to primarily mechanisms of hypertension. This has not been helpful. In the last 2 decades, appreciation that preeclampsia is a multisystemic syndrome characterized by vasoconstriction, metabolic changes, endothelial dysfunction, activation of the coagulation cascade, and increased inflammatory response, to mention only some of the organ systems involved, has redirected research. 5 As a result, progress in understanding the disorder has accelerated greatly, with attendant optimism for potentially effective treatments. 5 In this article, we consider this recent progress and its clinical implications.

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“…However, whether uric acid is an inactive, dead-end consequence of PE or a contributor to the disease is controversial (Kang et al 2004, Martin & Brown 2010. Evidence for a causal role of uric acid includes the following: (1) uric acid exerts pro-inflammatory and vasoconstrictive effects in rats (Kang et al 2004); furthermore, rats rendered hyperuricemic with uric acid, and uricase inhibitor administration develop hypertension and many other major features of preeclampsia, which is reversed by the xanthine oxidase inhibitor allopurinol (Mazzali et al 2001, Kang et al 2004; (2) elevation of uric acid levels in maternal plasma often precedes hypertension and proteinuria in humans (Powers et al 2006, Laughon et al 2011; (3) mechanistically, uric acid induces a pro-inflammatory, pro-contractile phenotype in vascular smooth muscle cells by activating NF-κB, AP-1 and MAPK (p38, ERK p42/p44) pathways and downstream expression of Cox-2, MCP-1, CRP and thromboxane A2, which plausibly contributes to many features of PE including inflammation (Kang et al 2002; (4) hyperuricemic rats have decreased placental activity of eNOS (Kang et al 2005), an enzyme catalyzing nitric oxide generation, which is a critical vasodilator for efficient placental perfusion given the absence of autonomic innervation in placenta; and (5) uric acid promotes the release of pro-inflammatory cytokines in rats challenged with LPS, and oppositely treatment of hyperuricemic rats with allopurinol or sodium bicarbonate, which decreases uric acid concentrations, decreases this inflammation (Netea et al 1997). This suggests that uric acid, once released by trophoblasts upon necrosis, may play a role in the pathogenesis of PE.…”

Section: Uric Acidmentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

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Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

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Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery

Cited by 139 publications

References 22 publications

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

Preeclampsia

Sterile inflammation and pregnancy complications: a review

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