In nephrotic syndrome, plasminogen is aberrantly filtered from plasma to the urinary space and activated along the tubular system. In vitro, plasmin increases ENaC current by proteolytic cleavage of the γ-subunit. It was hypothesized that preeclampsia is associated with plasmin-dependent ability of tubular fluid to activate ENaC. Urine was sampled from 16 preeclamptic (PE) patients and 17 normotensive pregnant women (Ctrl). Urine was analyzed for plasmin(ogen), creatinine, albumin, aldosterone, Na + , K + , proteolytic activity, and for its effect on inward current in cortical collecting duct cells (M1 cells) by whole-cell patch clamp. In PE, urine plasmin(ogen): creatinine ratio was elevated 40-fold (geometric mean, 160 versus 4 µg/g; P <0.0001) and urine aldosterone: creatinine ratio was suppressed to 25% of Ctrl (geometric mean, 27 versus 109 µg/g; P <0.001). A significant negative correlation was found in PE between urinary plasmin(ogen) and aldosterone ( P <0.05). In PE, proteolytic activity was detected at 90 to 75 kD by gelatin zymography in 14 of 16 patients and confirmed by serine protease assay. Immunoblotting showed active plasmin in PE urine. Whole-cell inward current increased in M1 cells on exposure to urine from PE (173±21%; n=6; P <0.001). The increase in current was abolished by amiloride (2 μmol/L; P <0.001), α 2 -antiplasmin (1 μmol/L; P <0.001), and heat denaturation ( P <0.001). Preeclampsia is associated with urinary excretion of plasmin(ogen) and plasmin-dependent activation of ENaC by urine. Proteolytic activation of ENaC by plasmin may contribute to Na + retention and hypertension in preeclampsia.

Preeclampsia is characterized by hypertension, proteinuria, suppression of plasma renin-angiotensin-aldosterone, and impaired urine sodium excretion. Aberrantly filtered plasmin in urine may activate proteolytically the γ-subunit of the epithelial sodium channel (ENaC) and promote Na reabsorption and urine K loss. Plasma and urine was sampled from patients with preeclampsia, healthy pregnant controls and non-pregnant women, and from patients with nephrostomy catheters. Aldosterone concentration, urine plasminogen, and protein were determined. Exosomes were isolated by ultracentrifugation. Immunoblotting was used to detect exosome markers; γ-ENaC (two different epitopes within the inhibitory peptide tract), α-ENaC, and renal outer medullary K-channel (ROMK) and compared with human kidney cortex homogenate. Urine total plasmin(ogen) was significantly increased in preeclampsia, plasma and urine aldosterone was higher in pregnancy compared to non-pregnancy, and the urine Na/K ratio was lower in preeclampsia compared to healthy pregnancy. Exosome markers ALIX and AQP-2 were stably associated with exosomes across groups. Exosomal α-ENaC-subunit migrated at 75 kDa and dominantly at 50 kDa and was significantly elevated in pregnancy. In human kidney cortex tissue and two of four pelvis catheter urine, ~90-100 kDa full-length γ-ENaC was detected while no full-length γ-ENaC but 75, 60, and 37 kDa variants dominated in voided urine exosomes. There was no difference in γ-ENaC protein abundances between healthy pregnancy and preeclampsia. ROMK was detected inconsistently in urine exosomes. Pregnancy and preeclampsia were associated with increased abundance of furin-cleaved α-ENaC subunit while γ-subunit appeared predominantly in cleaved form independently of conditions and with a significant contribution from post-renal cleavage.

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Preeclampsia is not associated with altered prostasin in placenta or plasma at term, but with increased prostasin in urine. An impact of prostasin-matriptase on placental development is likely to be at the level of activity and not protein abundance.

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BACKGROUNDElectronic fetal heart rate (FHR) monitoring, also known as fetal cardiotocography (CTG), monitors the FHR simultaneously with uterine contractions. This is an indirect assessment of the oxygenation and the wellbeing of the fetus during labour. Most commonly, the FHR is monitored externally using an ultrasonic Doppler device and the contractions are monitored concurrently via an external strain-gauge device.During labour, when a more precise record of fetal wellbeing and its capacity to withstand the rigours of labour is required, internal monitoring may provide more accurate monitoring information by applying an electrode to the fetal scalp. The electrode picks up the fetal ECG and the CTG monitor converts it 'beat-to-beat' into the FHR record.

Objective:The soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio has been introduced as a biomarker for diagnosing preeclampsia (PE) and the prediction of adverse pregnancy outcome. In a cohort of pregnant women with PE or at high risk of PE, the additive value of the sFlt-1/PlGF ratio for diagnosing PE and prediction of adverse pregnancy outcomes was investigated.Design and method: From September 2011 until August 2013 patients with suspected or confirmed clinical PE were recruited at the Erasmus MC. At time of admission, blood for measurement of sFlt-1 and PlGF was obtained. A sFlt-1/PlGF ratio of >85 was considered suggestive for PE. Clinical characteristics and pregnancy outcomes were retrieved from medical records. The clinical diagnosis of PE was made based on the ISSHP criteria, whereas the fullPIERS definition was used for the rating of adverse pregnancy outcomes.

Introduction Staff shortages and quality in obstetric care is a concern in most healthcare systems and a hot topic in the public debate that has centred on complaints about deficient care. However there has been a lack of empirical data to back the debate. The aim of this study was to analyse and describe complaints in obstetric care. Further, to compare the obstetric complaint pattern to complaints from women about other hospital services. Materials and Methods We used the Healthcare Complaints Analysis Tool to code, analyse and extract contents of obstetric complaint cases in a region of Denmark between 2016 and 2021. We compared the obstetric complaint pattern to all other hospital complaint cases in the same period regarding female patients at a large University Hospital in a cross-sectional study. Results Complaints regarding obstetric care differed from women’s complaints regarding other healthcare services. Women from obstetric care raised more problems per complaint, and tended to complain more about relational issues indicated by odds for complaints about staff shortage four times higher in the obstetric care group. Women from obstetric care had a lower proportion of compensation claims. Conclusion Systematic complaint analysis acknowledged women’s experience in obstetric care and may point to areas that, potentially need further attention. Complaints from obstetric care show that women experience deficiencies related to relational problems like recognition and individualized support compared to complaints from women receiving other hospital healthcare services.