Fractional excretion of tumor necrosis factor-α in women with severe preeclampsia

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-a 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-a 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-a was significantly lower (preeclampsia: 1.92% [0.46-4.20] versus control: 7.2% [2.44-12.07], P <.001). CONCLUSION: The fractional excretion of TNF-a 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.