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Objective The management and treatment of kidney disease has advanced, and women who are pregnant and give birth have also increased recently. On the other hand, pregnancy with kidney disease causes preeclampsia (19–30%), intrauterine fetal death (16–20%), postpartum renal failure (3–5%). The purpose of this study was to review the maternal and neonatal outcomes in pregnant women with chronic kidney disease (CKD), and to evaluate the appropriate management that may contribute to obstetric outcomes. Methods We conducted a retrospective review of 126 births and 129 neonates in 110 CKD patients who were seen at Osaka University Hospital between January, 2010, and December, 2017. Results The mean patient age was 33.5 (18–49) years, and the nulliparity rate was 61%. The most frequent disease was IgA nephropathy (43/126; 34%) and the second was lupus nephritis and renal transplantation (both were 15/126; 12%). Second trimester abortion and preterm delivery occurred in 5% and 20% of the patients, respectively. There was no maternal and neonatal death. Fetal growth restriction and preeclampsia occurred in 10% and 25% of the patients, respectively. Two patients with lupus nephritis and one with Henoch-Schönlein purpura nephritis had severe preeclampsia occurred before 20 weeks gestation. sFlt1/PlGF ratio were 427, 865 and 1183, respectively. Conclusions To predict and prevent the adverse events in the care of pregnant women with CKD is important for good maternal and neonatal outcomes. Furthermore, Henoch-Schönlein purpura nephritis that had been already ameliorated may be also a risk factor for severe preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction We have established a model of the maternal vascular endothelium using human umbilical vein endothelial cells (HUVECs), and shown that nicotine restores endothelial dysfunction caused by excess soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) via induction of placental growth factor (PIGF). Objectives In this study, we screened a library of 528 approved drugs to identify candidate compounds with therapeutic potential as preeclampsia treatments via their proangiogenic properties. Methods We assessed whether the screened drugs induced PIGF and restored damaged endothelial cell function using HUVECs. Enzyme-linked immunosorbent assays (ELISAs) were carried out to measure levels of PlGF in conditioned media treated with each drug (100 μmol/L) in the drug library. Tube formation assays were performed using HUVECs to evaluate the angiogenic effects of drugs that induced PlGF. We also performed ELISA, quantitative reverse transcription polymerase chain reaction, and tube formation assays after treatment with a range of concentrations of the candidate drug and with various combinations of sFlt1 (100 ng/mL), sEng (100 ng/mL). Results Of the drugs that induced PlGF, vardenafil was the only compound that significantly facilitated tube formation in comparison with the control cells ( P < .01). Treatment with vardenafil at concentrations of 50, 100, and 250 μmol/L increased expression of PlGF in a dose-dependent manner. Vardenafil (250 μmol/L) significantly improved tube formation which was inhibited in the presence of sFlt1 and/or sEng. Production of PlGF from HUVECs in the presence of sera derived from patients with preeclampsia was significantly elevated by administration of vardenafil (250 μmol/L). Conclusion By assessing drug repositioning through screening a library of approved drugs, we identified vardenafil as a potential protective agent against preeclampsia. The therapeutic mechanism of vardenafil may involve inhibition of the systemic maternal antiangiogenic state that leads to preeclampsia, in addition to its vasodilating effect. As concentrations used are high and unlikely to be useful clinically, further work is needed before testing it in humans. [ABSTRACT FROM AUTHOR]

Objective: Intrauterine infection such as by Escherichia coli and Ureaplasma spp induce placental inflammation and are one of the leading causes of preterm birth. Here we evaluated hydroxylated fullerene (C60[OH]44) for its in vitro antiinflammatory and antioxidant effects against host cellular responses to the ureaplasma toll-like receptor 2 (TLR2) ligand, UPM-1. In addition, we investigated the preventative effects of C60(OH)44 in vivo in a mouse preterm birth model that used UPM-1.Study Design: TLR2-overexpressing cell lines and the primary cultures of mouse peritoneal macrophages were pretreated with C60(OH)44. After UPM-1 addition to the cell lines, the activation of the nuclear factor kappa-light chain-enhancer of activated B cells (NF-kappaB) signaling cascade and the production of reactive oxygen species were monitored. The levels of expression of inflammatory cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and the production of reactive oxygen species were quantified after stimulation with UPM-1. The in vivo preventative effects of C60(OH)44 on mice preterm birth were evaluated by analyzing the preterm birth rates and fetal survival rates in the preterm birth mouse model with placental histological analyses.Results: Pretreatment with C60(OH)44 significantly suppressed UPM-1-induced NF-kappaB activation and reactive oxygen species production in TLR2-overexpressing cell lines. In the primary culture of mouse peritoneal macrophages, UPM-1-induced production of reactive oxygen species and the expression of inflammatory cytokines such as IL-6, IL-1β, and TNF-α were significantly reduced by pretreatment with C60(OH)44. In the UPM-1-induced preterm birth mouse model, the preterm birth rate decreased from 72.7% to 18.2% after an injection of C60(OH)44. Placental examinations of the group injected with C60(OH)44 reduced the damage of the spongiotrophoblast layer and reduced infiltration of neutrophils.Conclusion: C60(OH)44 was effective as a preventative agent of preterm birth in mice. [ABSTRACT FROM AUTHOR]

Objectives In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin and that nicotine inhibits interleukin 6 (IL-6) productions which maternal serum stimulates. Methods Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells (HUVECs) treated with nicotine, and with various combinations of soluble fms-like tyrosine kinase 1, soluble endoglin, and nicotine. Enzyme-linked immunosorbent assay (ELISA) was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor- 1 concentrations in the conditioned media treated with nicotine. HUVECs were incubated with or without 0.5% serum from healthy pregnant women at term and treated with or without nicotine in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. IL-6 concentration and nuclear transcription factor kappa B (NF-kB) activities were determined by ELISA-based method. Results Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fms-like tyrosine kinase 1 and/or soluble endoglin reduced endothelial functions. Placental growth factor, but not transforming growth factor-1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable. IL-6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-kB activation in endothelial cells. Conclusions Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia. Disclosures K. Mimura: None. T. Tomimatsu: None. T. Kimura: None. [ABSTRACT FROM AUTHOR]

Objective: In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin. Study Design: Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells treated with nicotine (10−9 to 10−6 M), and with various combinations of soluble fms-like tyrosine kinase 1 (100 ng/mL), soluble endoglin (100 ng/mL), and nicotine (10−7 M). Enzyme-linked immunosorbent assay was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor-β1 concentrations in the conditioned media treated with nicotine (10−9 to 10−6 M). Results: Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fms-like tyrosine kinase 1 and/or soluble endoglin-reduced endothelial functions. Placental growth factor, but not transforming growth factor-β1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable. Conclusion: Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia. [Copyright &y& Elsevier]