Soluble Flt‐1, Placental Growth Factor, and Vascular Endothelial Growth Factor Serum Levels to Differentiate Between Active Lupus Nephritis During Pregnancy and Preeclampsia

Abstract

Objective To evaluate mean serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble Flt‐1 (sFlt‐1) in pregnant patients with systemic lupus erythematosus (SLE) with inactive disease, active lupus nephritis, and preeclampsia for differential diagnosis between these conditions. Methods Pregnant women with SLE, with singleton pregnancies and no other autoimmune diseases, were classified according to disease activity (inactive SLE and active lupus nephritis) and the presence of preeclampsia. Serum samples were collected within 3 weeks of delivery and frozen for subsequent blinded analysis through the enzyme‐linked immunosorbent assay method. Results A total of 71 women were included, with 41 classified as having inactive SLE (group 1; Systemic Lupus Erythematosus Pregnancy Disease Activity Index [SLEPDAI] score <4), 15 with a diagnosis of active lupus nephritis (group 2, SLEPDAI score ≥4, including renal criteria), and 15 with a diagnosis of preeclampsia (group 3). Patients in group 3 had higher mean levels of sFlt‐1 and lower mean levels of PlGF compared to groups 1 and 2, both findings with statistical significance. The sFlt‐1:PlGF ratio was also significantly higher in patients with preeclampsia, while mean VEGF levels were higher in pregnant woman with active lupus nephritis compared to patients with preeclampsia or inactive SLE. Conclusion Evaluation of serum VEGF, PlGF, and sFlt‐1 levels can differentiate between preeclampsia, inactive SLE, and active lupus nephritis during pregnancy.

Vascular Endothelial Growth Factor Biology and Its Potential as a Therapeutic Target in Rheumatic Diseases

“…Recent publications showed that there is a significant difference in VEGF level between preeclampsia, inactive SLE, and active lupus nephritis. So, this result suggests that VEGF level may be a useful marker to clinicians [111]. Lupus nephritis is a severe manifestation and prognosis in patients with SLE.…”

Chronic kidney disease and pregnancy outcomes

“…The literature consensus of the authors is that currently the assessment of sflt-1/PlGF levels may help to differentiate the two situations, where a negative ratio may indicate the absence of the development of preeclampsia 18 . Research in this field points to the possibility of using the sflt-1/PlGF ratio to distinguish pre-eclampsia from active lupus nephritis 19 . The sflt-1/PlGF ratio can be used to differentiate between preeclampsia and nephropathy and this laboratory method is now routinely used to discriminate severe endothelial dysfunction accompanying possible preeclampsia.…”

Atypical preeclampsia with systemic lupus erythematosus and elevated soluble fms‐like tyrosine kinase 1/placental growth factor ratio

“…6 Recently, the usefulness of the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in differentiating preeclampsia from exacerbation of an underlying disease has been suggested. 3,7 In the present study, we report three cases of SLE pregnancies that were considered to be complicated by atypical preeclampsia before 20 weeks of gestation. In all three cases, sFlt-1 and PlGF were measured using a commercial automated electrochemiluminescence immunoassay (SRL, Tokyo, Japan) and the sFlt-1/PlGF ratio was markedly elevated.…”