Circulating angiogenic factors in preeclampsia, gestational proteinuria, and preeclampsia superimposed on chronic glomerulonephritis

Masuyama, Hisashi; Suwaki, Naoko; Nakatsukasa, Harushige; Masumoto, Akio; Tateishi, Yoko; Hiramatrsu, Yuji

doi:10.1016/j.ajog.2005.08.034

Cited by 91 publications

(69 citation statements)

References 20 publications

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“…[16][17][18] Moreover, recent reports have indicated that the soluble form of the VEGF receptor-1 (sFlt-1) is increased in the placenta and serum of women with PE. [18][19][20][21] Thus, sFlt-1 may act by sequestering free PlGF and free VEGF, thereby preventing interaction between endothelial Median (interquartile range).…”

Section: Discussionmentioning

confidence: 99%

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Masuyama

Segawa

Sumida

et al. 2010

BJOG

109

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Objective Circulating angiogenic factors have been shown to be important in the pathophysiology of pre-eclampsia. Blood levels of adipocytokines differ in pre-eclampsia relative to controls and may also play an important role in disease pathogenesis. Differences in the circulating levels of these molecules were compared between matched normotensive controls and women with pre-eclampsia with onset before or at/after 32 weeks, and according to whether the women were of normal weight (18.5 < body mass index < 25) or overweight.Design A cross-sectional study of 110 pregnant Japanese women who visited the Department of Obstetrics and Gynecology, Okayama University Hospital, Okayama, Japan.Setting Tertiary referral centre serving 2000 births.Methods Serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sEng), adiponectin and leptin were measured in women with pre-eclampsia and in normotensive controls matched for age, gestational week, parity and body mass index.Main outcome measures Serum levels of sFlt-1, PlGF, the sFlt-1/ PlGF ratio, sEng, adiponectin and leptin.Results The sFlt-1/PlGF ratio in early-onset pre-eclampsia was significantly higher than that in late-onset pre-eclampsia (112.0 ± 30.2 versus 45.4 ± 43.8, P = 0.037). There was a significant elevation of leptin in both subtypes relative to controls (early: 58.6 ± 18.3 ng/ml versus 26.0 ± 6.7 ng/ml, P = 0.001; late: 39.5 ± 9.2 ng/ml versus 22.0 ± 4.3 ng/ml, P = 0.005), but adiponectin was increased only in late-onset pre-eclampsia (36.5 ± 13.4 lg/ml versus 12.0 ± 4.3 lg/ml, P = 0.003). Significant differences in angiogenic factors and adiponectin were found between normal and overweight women only in late-onset pre-eclampsia.Conclusions These data suggest that there are different profiles of angiogenic factors and adipocytokines between women who develop early-and late-onset pre-eclampsia.

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Section: Discussionmentioning

confidence: 99%

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Masuyama

Segawa

Sumida

et al. 2010

BJOG

109

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“…19 Circulating sFlt-1 and PlGF levels are also altered in women with gestational proteinuria, but to a lesser degree than in those with pre-eclampsia. 20,21 In this study, we determined serum sFlt-1 and PlGF levels in healthy non-pregnant and pregnant women and pre-eclamptic patients. We also measured several markers of processes involved in the pathogenesis of pre-eclampsia, and investigated whether the clinical characteristics and laboratory parameters of the study participants, including markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen (VWF:Ag)) and endothelial injury (fibronectin), oxidative stress (malondialdehyde) and trophoblast debris (cell-free fetal DNA), were related to their serum sFlt-1 and PlGF levels.…”

Section: Introductionmentioning

confidence: 99%

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

et al. 2010

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The purpose of this study was to determine whether increased serum soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF) levels in pre-eclampsia are related to the clinical features and laboratory parameters of the patients, including markers of inflammation, endothelial activation and injury, oxidative stress and trophoblast debris. A total of 54 pre-eclamptic patients, 58 healthy pregnant and 52 healthy non-pregnant women were involved in this case-control study. Serum sFlt-1 and PlGF levels were measured by electrochemiluminescence immunoassay. Serum levels of sFlt-1 and PlGF were significantly higher in pre-eclamptic patients and healthy pregnant women than in healthy non-pregnant women. In addition, pre-eclamptic patients had significantly higher sFlt-1 levels and significantly lower PlGF concentrations compared with healthy pregnant women. According to the subgroup analyses, sFlt-1 levels were significantly higher in severely pre-eclamptic patients than in those with mild pre-eclampsia, whereas pre-eclamptic patients with fetal growth restriction or preterm onset of the disease had significantly lower PlGF concentrations compared with those without intrauterine growth restriction or with a disease onset at term. In the pre-eclamptic group, there were significant positive correlations between serum sFlt-1 levels and systolic and diastolic blood pressure, serum levels of blood urea nitrogen and creatinine, as well as plasma levels of von Willebrand factor antigen, fibronectin and cell-free fetal DNA. Furthermore, serum PlGF concentrations of pre-eclamptic patients showed significant positive correlations with gestational age at disease onset and delivery, as well as with fetal birth weight, and significant inverse correlations with levels of blood urea nitrogen, creatinine and fibronectin. In conclusion, increased serum sFlt-1 and decreased PlGF levels are associated with blood pressure, renal and endothelial dysfunction, trophoblast deportation, as well as with a shorter duration of pregnancy, fetal growth restriction, the severity and preterm onset of the disease in pre-eclampsia. These findings indicate the central role of an angiogenic imbalance in the pathogenesis of this pregnancy-specific disorder.

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“…We must consider how serum levels of sFlt-1 and sEng change in pregnant women with chronic nephritis when they show deterioration of proteinuria during pregnancy. Masuyama et al [3] indicated that the levels of sFlt-1 and sEng might not be increased in severe proteinuria due to chronic glomerulonephritis; five women with chronic glomerulonephritis showing severe proteinuria without hypertension had the same level of sFlt-1 and sEng as five women with chronic glomerulonephritis showing a normal clinical course. In short, while GP might show elevated sFlt-1 and sEng [2], glomerulonephritis, even with severe proteinuria during pregnancy, might not [3].…”

Section: Discussionmentioning

confidence: 99%

“…While GP might show elevated levels, nephritis might not; however, this notion is not widely known, and few studies have focused on it [2,3]. Here, we present a woman for whom their measurement may have contributed to deciding not to perform kidney biopsy, leading to nonadministration of steroids.…”

Section: Introductionmentioning

confidence: 94%

Increased antiangiogenetic factors in severe proteinuria without hypertension in pregnancy: is kidney biopsy necessary?

et al. 2013

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Acute onset of severe proteinuria during pregnancy obliges physicians to clinically discriminate between gestational proteinuria (GP) and new onset of nephritis. A multiparous woman developed severe proteinuria (5.8 g/ day) without hypertension at 32 weeks of gestation. We measured the maternal level of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng), which were extremely high (41.3 and 54.8 ng/ml, respectively), leading us to consider this condition as GP rather than acute onset of nephritis. Thus, we did not perform a kidney biopsy and did not administer a steroid agent. Non-reassuring fetal status required emergency Cesarean section at 33 weeks. Proteinuria decreased to 0.36 g/day at 12 weeks after delivery, and finally disappeared 26 weeks postpartum. Measurement of sFlt-1 and sEng in a pregnant woman with severe proteinuria without hypertension may assist in differential diagnosis of GP from acute onset of nephritis, and thus help to decide whether to perform kidney biopsy during pregnancy.

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Circulating angiogenic factors in preeclampsia, gestational proteinuria, and preeclampsia superimposed on chronic glomerulonephritis

Cited by 91 publications

References 20 publications

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

Increased antiangiogenetic factors in severe proteinuria without hypertension in pregnancy: is kidney biopsy necessary?

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