title: Fractional excretion of tumor necrosis factor-alpha in women with severe preeclampsia.
abstract: OBJECTIVE
  Proinflammatory cytokines of placental or systemic origin are thought to play a central role in the pathophysiology of preeclampsia. We sought to estimate the fractional excretion of tumor necrosis factor (TNF)-alpha in relationship to proteinuria in women with severe preeclampsia.
  
  
  METHODS
  In a cross-sectional study, we evaluated the serum and urine levels of TNF-alpha in 45 women diagnosed with severe preeclampsia (mean+/-standard error of the mean, gestational age 29.1+/-0.5 weeks). Forty-five healthy pregnant women matched for parity, maternal age, and gestational age at recruitment (30.1+/-0.4 weeks) made up the control group. Urinary concentrations were normalized to creatinine. The fractional excretion of TNF-alpha was interpreted in relationship to that of total proteins and soluble fms-like tyrosine kinase-1 (sFlt-1).
  
  
  RESULTS
  We found that the women with preeclampsia had significantly higher serum TNF-alpha concentrations compared with the women in the control group (mean+/-standard error of the mean, preeclampsia: 1.39+/-0.09 versus control: 0.93+/-0.07 pg/mL, P<.001). In contrast, urinary levels of TNF-alpha were significantly decreased in the women with preeclampsia compared with the healthy women (median [interquartile range], preeclampsia: 0.26 [0.10-0.91] versus control: 0.58 [0.21-1.29] pg/mg creatinine, P=.003), even though the hypertensive women had higher levels of proteinuria. In contrast to sFlt-1, urinary TNF-alpha did not correlate with the degree of proteinuria. Additionally, in preeclampsia, the fractional excretion of TNF-alpha was significantly lower (preeclampsia: 1.92% [0.46-4.20] versus control: 7.2% [2.44-12.07], P<.001).
  
  
  CONCLUSIONS
  The fractional excretion of TNF-alpha is significantly reduced in women with severe preeclampsia despite proteinuria. The decreased clearance and altered renal excretion of this cytokine may contribute to the exaggerated inflammatory response observed in preeclampsia.
  
  
  METHODS
  II.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA. michael.cackovic@yale.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Cackovic
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Funai
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
authors.forename: Edward
authors.initials: E
authors.lastname: Kuczynski
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D011225:Pre-Eclampsia / Q000097:blood / Q000276:immunology / Q000652:urine*; D011247:Pregnancy; D011507:Proteinuria / Q000097:blood / Q000652:urine*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000652:urine*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine