Fractional excretion of angiogenic factors in women with severe preeclampsia.
OBJECTIVE
We estimated the fractional excretions of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor, and placental growth factor of severely preeclamptic women at the time of disease clinical manifestation.


METHODS
Levels of free sFlt-1, vascular endothelial growth factor, and placental growth factor were measured by immunoassay from time-matched serum-urine samples from 64 women in the following groups: nonpregnant reproductive aged (n = 9), healthy pregnant controls (n = 13), mildly preeclamptic women (n = 15), and women with severe preeclampsia (n = 27). Urinary concentrations of angiogenic factors were normalized to creatinine and fractional excretions calculated. Correlations were estimated between fractional excretions of angiogenic factors, albuminuria, nonspecific proteinuria and urine protein-to-creatinine ratio.


RESULTS
Severely preeclamptic women had more than double urinary vascular endothelial growth factor (P = .01) and fractional excretion of vascular endothelial growth factor compared with mildly preeclamptic women (P = .007) or pregnant controls (P < .001). Serum, urine and fractional excretion levels of sFlt-1 were much higher among severely preeclamptic women compared with all the other pregnant groups (P < .001). Conversely, severely preeclamptic women had lower serum placental growth factor levels compared with healthy pregnant women (P < .05) and mildly preeclamptic groups (P < .05). Severely preeclamptic women had increased fractional excretions of placental growth factor, albumin, proteinuria, and random urine total protein/creatinine ratio. Among severely preeclamptic women there was no correlation between proteinuria and fractional excretion of vascular endothelial growth factor (r = 0.30, P = .127) or sFlt-1 (r = 0.35, P = .07). There was a significant correlation between fractional excretion for placental growth factor, random urine total protein/creatinine ratio (r = 0.60, P = .002), and nonspecific proteinuria (r = 0.50, P = .01).


CONCLUSIONS
Severe preeclampsia is characterized by increased fractional excretion of angiogenic factors and especially of vascular endothelial growth factor, likely reflecting 2 separate phenomena that may have additive effects: "endogenous" renal production and glomerular "leakage."
Buhimschi
Catalin S
CS
Department of Obstetrics, Gynecology and Reproductive Science, Yale University, New Haven, Connecticut 06520, USA. catalin.buhimschi@yale.edu
Magloire
Lissa
L
Funai
Edmund
E
Norwitz
Errol R
ER
Kuczynski
Edward
E
Martin
Ryan
R
Richman
Susan
S
Guller
Seth
S
Lockwood
Charles J
CJ
Buhimschi
Irina A
IA
D000328:Adult; D000419:Albuminuria; D016022:Case-Control Studies; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012709:Serum Albumin; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D003404:Creatinine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1