Treatment of very preterm preeclampsia via heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) apheresis: The Freiburg preeclampsia H.E.L.P.-Apheresis study.

OBJECTIVE: Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1. STUDY DESIGN: Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (<28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored. MAIN OUTCOME MEASURES: In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected. CONCLUSIONS: H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

[Fetal renal failure after intrauterine exposure to inhibitors of the renin-angiotensin system]. / Fetale Niereninsuffizienz bei Therapie mit Hemmstoffen des Renin-Angiotensin-Systems in der Schwangerschaft.

UNLABELLED: HISTORY AND AIM: A 36-year-old woman (primigravida, nullipara) at 25 + 3 weeks of gestation and a 27-year-old (primigravida, nullipara) at 22 + 7 weeks of gestation presented with oligo-/anhydramnios at our department of obstetrics. Both patients suffered from diabetes type 1 and 2, respectively, complicated by diabetic nephropathy, renal hypertension and retinopathy. The first woman had received an AT1 receptor antagonist and a beta blocker, the other one an ACE inhibitor and a beta blocker. At initial clinical examination both patients were in a good general state of health. Respiration, pulse and blood pressure were within normal limits. INVESTIGATIONS: Sonography showed oligy-/anhydramnion with enlarged echogenic kidneys of both fetuses. Having ruled out premature rupture of the membranes the reduced amount of amniotic fluid was interpreted as a consequence of the antihypertensive medication. TREATMENT AND COURSE: The medication was changed to methyldopa which resulted in an adequate and moderate increase of amniotic fluid in both patients. At post partum examination renal failure was confirmed in both infants. The first infant, now a boy at the age of two years, still suffers from chronic renal failure, needing antihypertensive medication with an ACE blocker. Follow-up of the second baby has so far shown normal growth of the kidneys and normotensive blood pressure. CONCLUSION: When planning a pregnancy, a preexisting hypertension should be treated with either methyldopa (1st choice) or a beta blocker as a second choice (e. g. Metoprolol). In patients who are treated with ACE blockers or AT1 antagonists, medication should be changed as soon as the pregnancy is ascertained.