Pre-eclampsia part 1: current understanding of its pathophysiology

Nat Rev Nephrol. 2014 Aug;10(8):466-80. doi: 10.1038/nrneph.2014.102. Epub 2014 Jul 8.

Abstract

Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adult
  • Animals
  • Endoplasmic Reticulum Stress
  • Endothelial Cells / physiology
  • Female
  • Fetal Growth Retardation
  • Humans
  • Hypertension / etiology*
  • Kidney / physiopathology
  • Oxidative Stress
  • Platelet Activation
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Pregnancy Trimester, Second
  • Proteinuria / etiology*
  • Receptor, Angiotensin, Type 1 / immunology
  • Uterus / blood supply
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

  • Receptor, Angiotensin, Type 1
  • Vascular Endothelial Growth Factor Receptor-1