Anti-angiogenic assay assists fetal extraction decision in a case of pre-eclampsia suspicion?

Sir, The diagnosis of superimposed pre-eclampsia can be difficult when there is already pre-existing hypertension and a pre-existing glomerular kidney disease with significant proteinuria [1]. Case. We report the case of a 25-year-old woman, for whom a non-proliferative IgA nephropathy with a serum creatinine at 103 μmol/L, a nephrotic range proteinuria, no hypertension and no hyperuricaemia was discovered at the beginning of her first pregnancy. The evolution was characterized by the onset of hyperuricaemia at 19 weeks of gestation followed by an excess weight gain with oedema, hypertension and deterioration of the renal function with a serum creatinine value increasing to 140 µmol/L. To help us to distinguish superimposed pre-eclampsia from isolated worsening renal disease associated with hypertension and to better assess the evolution of the disease, circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) were measured serially by Quantikine immunoassays (R&D Systems) at 34 weeks plus 2 days, 34 weeks plus 6 days and 35 weeks. The high value of the first sample at 4193 pg/mL and the trend towards an increase with the second sample at 4446 pg/mL (even though the last value was at 3714 pg/mL) associated with concomitant threatening functional clinical manifestations of hypertension led us to perform delivery at 35 weeks by Caesarean section with the birth of a healthy baby weighing 2.5 kg. The post-partum period was characterized by a fall in circulating levels of sFlt-1, immediately after delivery, with values at 888, 667 and 123 pg/mL. Conversely, serum creatinine and uric acid remained unchanged, 30 days after delivery at 141 and 428 µmol/L, respectively. Comment. This case illustrates the difficulty in differentiating a superimposed pre-eclampsia from an isolated deterioration of a pre-existing renal disease during pregnancy. The increase in serum uric acid can be explained by a superimposed pre-eclampsia or by the impact of pregnancy in worsening pre-existing nephropathy, similar to the onset of hypertension. The high levels of circulating sFlt-1 found before delivery were in the same range as the mean serum level of 4382 pg/mL found by Levine et al. in the group of women with pre-eclampsia at a similar gestational age (as compared with 1643 pg/mL, in the control group of women with normal pregnancy) and strongly suggests an excess placental production related with superimposed pre-eclampsia [2,3]. Because of the possibility of false-positive values, histological placenta data would have been better to confirm the diagnosis [4]. Unfortunately, the latter was not preserved. However, these high levels of circulating sFlt-1 cannot account for the concomitant renal dysfunction. Indeed, renal failure is usually associated with a significant, but very moderate, increase in circulating sFlt-1 [5]. Moreover, in the present case, circulating levels of sFlt-1 fall rapidly after delivery despite the persistence of renal failure and hyperuricaemia. Variations of sFlt-1-circulating levels have been mainly studied among population groups of gestational women. The present case demonstrates that the results of several sFlt-1-circulating assays performed on the same patient can also assist better birth management in difficult situations. Conflict of interest statement. None declared.