Preeclampsia: a renal perspective.

Preeclampsia, a pregnancy-specific syndrome of hypertension and proteinuria, is characterized by defective placental vasculogenesis and widespread maternal endothelial dysfunction. Although the manifestations of preeclampsia are primarily maternal, the burden of morbidity and mortality is often on the neonate, since the only effective treatment-delivery of the fetus and placenta-often results in iatrogenic prematurity. In this review, we summarize recent advances in our understanding of the pathophysiology of preeclampsia, including normal and aberrant placental vascular development and evidence for endothelial dysfunction. We describe recent evidence that supports a novel mechanism in which a maladaptive shift in placental production of angiogenic factors such as soluble fms-like tyrosine kinase 1 (a circulating antiangiogenic protein) may play an important role in the pathogenesis of preeclampsia.

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Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia.

Reduced umbilical and placental vascular prostacyclin in severe pre-eclampsia

The coagulation and fibrinolytic mechanisms were investigated in a group of patients with severe pre-eclampsia and eclampsia and the findings were compared with those of healthy women in late pregnancy. In patients with pre-eclampsia the following significant differences were found: (1) greater depression of plasma fibrinolytic activity (euglobulin lysis time) than in normal pregnancy, (2) a higher level of inhibitor to urokinaseinduced lysis, (3) increased levels of serum fibrin degradation products, and (4) reduced platelet counts.In patients with eclampsia a progressive increase of the level of serum fibrin degradation products was found over the three days following eclamptic seizures. No such increase occurred after grand mal seizures in late pregnancy. The findings in this study support the view that intravascular clotting is taking place in pre-eclampsia and that this disturbance of the balance between coagulation and fibrinolysis may be localized to certain areas of the vascular compartment, particularly the placental and renal circulations. Fibrin deposition in the maternal vessels supplying the placenta would impair the placental blood flow, which may explain the placental insufficiency which occurs in pre-eclampsia. Likewise fibrin deposition in the renal vasculature will result in glomerular damage and proteinuria. Hypertension may be related to the renal ischaemic changes or a compensatory response to the presence of fibrin deposition in the vascular compartment. This evidence of intravascular fibrin deposition raises the question of the possible therapeutic value of antithrombotic agents to inhibit the clotting process. On a theoretical basis such treatment might be expected to improve blood flow to the placenta and thereby fetal growth.

https://www.bmj.com/content/bmj/2/5752/12.full.pdf

Coagulation and Fibrinolytic Systems in Pre-eclampsia and Eclampsia

Publisher Summary This chapter discusses the interdependency of the blood clotting process, fibrinolytic phenomena, inflammation, and immunologic reactions. The chapter discusses some of the ways in which the body responds to injuries or to harmful agents. The chapter describes the vantage point of the coagulationist some ways in which hemostasis and its ally—fibrinolytic phenomena—influence inflammation and immune mechanisms. Hemostasis is a complex process that attracts the attention of immunologists. The interesting parallels and at times direct interrelationships of hemostasis and serologic events initiated by antigen–antibody reactions are now apparent. The chapter also provides the basis for a clear understanding of the many elements of hemostasis and a perspective that views the several defense mechanisms as a well-integrated continuum. The chapter provides some of the valuable information available in present scenario concerning the relationships among the blood-clotting process, fibrinolytic phenomena, the inflammatory response, and immune mechanisms.

Beller Fk

Papers

Immunofluorescent studies of renal biopsies in the diagnosis of toxemia of pregnancy.