Differential Diagnosis of Preeclampsia

Verdonk, Koen; Visser, Willy; Russcher, Henk; Danser, A.H. Jan; Steegers, Eric A.P.; Meiracker, Anton H. van den

doi:10.1161/hypertensionaha.112.201459

Cited by 35 publications

(13 citation statements)

References 43 publications

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Section: Discussionsupporting

confidence: 57%

“…It also minimizes the risk of including patients with preexisting disease such as systemic lupus erythematosus. 13 However, it should be noted here that a reanalysis on the basis of a subdivision according clinical diagnosis yielded identical results (data not shown).A high antiangiogenic state, as reflected by elevated sFlt-1 levels, is associated with increased ET-1 levels. Given the observation that ET-1 also rises in patients with cancer and rats treated with the VEGF inhibitor sunitinib ( Figure 1A), 6 the most logical explanation of this ET-1 rise is that it is the direct consequence of VEGF inhibition, either through VEGF inactivation by sFlt-1 (in preeclampsia) or through interference with VEGF signaling (with sunitinib).…”

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confidence: 58%

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Association Studies Suggest a Key Role for Endothelin-1 in the Pathogenesis of Preeclampsia and the Accompanying Renin–Angiotensin–Aldosterone System Suppression

et al. 2015

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P reeclampsia is a pregnancy-related disorder, clinically characterized by the new onset of proteinuria and hypertension in the second half of pregnancy, with a great effect on maternal and fetal morbidity and mortality worldwide. 1A better understanding of the pathogenic mechanisms underlying preeclampsia might help identifying biomarkers that allow early diagnosis and treatment of preeclampsia. Recently, disturbances in angiogenic balance (favoring antiangiogenic over proangiogenic factors), elevated endothelin-1 (ET-1) levels, and a suppressed renin-angiotensin-aldosterone system (RAAS) have been reported. [2][3][4] As a consequence, the ratio of the antiangiogenic soluble Fms-like tyrosine kinase-1 (sFlt-1) and the proangiogenic placental growth factor (PlGF) is now thought to be a reliable biomarker for the diagnosis of preeclampsia. 5 In fact, patients with a ratio ≥85 have a poor pregnancy outcome independent of their clinical diagnosis compared with patients with a ratio <85. 5Of interest, treatment of cancer patients with antiangiogenic drugs (which, like sFlt-1, prevent the actions of vascular endothelial growth factor [VEGF]) resulted in hypertension, proteinuria, renin suppression, and elevated ET-1 levels. 6 Animal studies with antiangiogenic drugs additionally revealed that the renal histological changes observed during such treatment, in particular glomerular endotheliosis, resembled the renal alterations observed in preeclampsia. 7 From the observation that the dual ET A/B receptor antagonist macitentan prevented both the rise in blood pressure and proteinuria during Abstract-Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and reninangiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomer...

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Section: Discussionsupporting

confidence: 57%

supporting

confidence: 58%

Association Studies Suggest a Key Role for Endothelin-1 in the Pathogenesis of Preeclampsia and the Accompanying Renin–Angiotensin–Aldosterone System Suppression

et al. 2015

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“…The soluble fms-like tyrosine kinase 1/placental growth factor ratio defined by Verdonk et al may also help identify a disease flare-up. 23) Pregnancy in SLE patients is considered high risk, and management should start before conception. Pregnancy should be planned when patient health is optimal, i.e., when the disease is in clinical remission for at least 6 months, and while on a decreased steroid dosage.…”

Section: Discussionmentioning

confidence: 99%

Disease flare-ups and obstetric outcomes in pregnant women with systemic lupus erythematosus

Takahashi

Mimura

Kanagawa

et al. 2013

Hypertens Res Pregnancy

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Aim:The purpose of this study was to review the maternal and fetal outcomes in pregnant women with systemic lupus erythematosus (SLE), and to evaluate the prognostic risk factors that may contribute to obstetric outcomes or SLE flareups. Methods: We evaluated 100 births in 97 SLE patients who were seen at Osaka University from 1995 to 2013. Main outcome measures included obstetric outcomes and SLE flare-ups. Results: The mean patient age was 30.7 ± 4.6 years, and the nulliparity rate was 62.8%. Corticosteroids were taken by 75.3% of the patients, and 48.5% were on a dosage of ≥ 7.5 mg /day. Disease flare-up and preeclampsia occurred in 17.5% and 11.3% of the patients, respectively. Seven SLE flare-ups (41.2%) occurred after delivery. Fourteen of the patients with a flare-up were taking high dose corticosteroids ( ≥ 7.5 mg /day) and showed significantly poorer obstetric outcomes compared to patients taking low dose corticosteroids ( < 7.5 mg /day) (P = 0.0021). Conclusions: A multidisciplinary approach in the care of pregnant women with SLE is important for good maternal and fetal outcomes. Furthermore, a high daily dosage of corticosteroids may be a prognostic risk factor for adverse SLE flare-ups.

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“…[67][68][69][70][71] Angiogenic markers have also been shown to be promising in preeclampsia-related disorders, such as idiopathic fetal growth restriction and stillbirth. 72,73 To demonstrate clinical use of these biomarkers, we led a large clinical study to evaluate the role of angiogenic biomarkers in the prediction of preeclampsia-related adverse outcomes among women evaluated at our institution for suspected preeclampsia.…”

Section: Biomarker Studies In Preeclampsiamentioning

confidence: 99%