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Obstetrics & Gynecology 2008;112:93-100
© 2008 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Fractional Excretion of Tumor Necrosis Factor-{alpha} in Women With Severe Preeclampsia

Michael Cackovic, MD, Catalin S. Buhimschi, MD, Guomao Zhao, BSc, Edmund F. Funai, MD, Errol R. Norwitz, MD, PhD, Edward Kuczynski, Charles J. Lockwood, MD and Irina A. Buhimschi, MD

From the Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.

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).

CONCLUSION: 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.

LEVEL OF EVIDENCE: II






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