title: Association of preeclampsia with podocyte turnover.
abstract: OBJECTIVE
  Preeclampsia is characterized by hypertension and proteinuria, and increased shedding of podocytes into the urine is a common finding. This finding raises the question of whether preeclamptic nephropathy involves podocyte damage. This study examined podocyte-related changes in a unique sample of renal tissues obtained from women who died of preeclampsia.
  
  
  METHODS
  All patients with preeclampsia who died in The Netherlands since 1990 and had available autopsy tissue were identified using a nationwide database of the Dutch Pathology Registry (PALGA). This resulted in a cohort of 11 women who died from preeclampsia. Three control groups were also identified during the same time period, and consisted of normotensive women who died during pregnancy (n=25), and nonpregnant controls either with (n=14) or without (n=13) chronic hypertension. Glomerular lesions, including podocyte numbers, podocyte proliferation, and parietal cell activation, were measured.
  
  
  RESULTS
  Patients with preeclampsia had prominent characteristic glomerular lesions. The results showed that the number of podocytes per glomerulus did not differ significantly between the patients with preeclampsia and the control groups. However, preeclampsia was associated with a significant increase in intraglomerular cell proliferation (7.3% [SD 9.4] of the glomeruli of patients with preeclampsia had Ki-67-positive cells versus 1.6% [SD 3.3] of the glomeruli of hypertensive controls and 1.1% [SD 1.3] of nonpregnant controls; P=0.004) and activated parietal epithelial cells on a podocyte location (34% [SD 13.1] of the glomeruli of patients with preeclampsia versus 18.0% [SD 15.3] of pregnant controls, 11.9% [SD 13.2] of hypertensive controls, and 10.8% [SD 13.4] of nonpregnant controls; P=0.01).
  
  
  CONCLUSIONS
  These findings suggest that the recently described mechanisms of podocyte replacement play a role in preeclampsia. These results provide key new insights into the pathogenesis of preeclamptic nephropathy, and they open new possibilities for developing therapeutic modalities.
authors.affiliation: Departments of Pathology and m.e.penning@lumc.nl.
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Penning
authors.affiliation: Obstetrics, Leiden University Medical Center, Leiden, The Netherlands; and.
authors.forename: Kitty W M
authors.initials: KW
authors.lastname: Bloemenkamp
authors.affiliation: Departments of Pathology and.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Zon
authors.affiliation: Departments of Pathology and.
authors.forename: Malu
authors.initials: M
authors.lastname: Zandbergen
authors.affiliation: Department of Obstetrics and Gynecology, Isala Zwolle, Zwolle, The Netherlands.
authors.forename: Joke M
authors.initials: JM
authors.lastname: Schutte
authors.affiliation: Departments of Pathology and.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.affiliation: Departments of Pathology and.
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.affiliation: Departments of Pathology and.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Baelde
mesh_terms: D000328:Adult; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002423:Cause of Death; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009426:Netherlands; D050199:Podocytes / Q000737:chemistry / Q000473:pathology*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011247:Pregnancy; D012042:Registries
chemical_list: D015415:Biomarkers; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen
keywords: kidney; podocyte; renal epithelial cell; target organ damage