Second-trimester urine nephrin:creatinine ratio versus soluble fms-like tyrosine kinase-1:placental growth factor ratio for prediction of preeclampsia among asymptomatic women

Abstract

This prospective observational study compare urine nephrin:creatinine ratio (NCR, ng/mg) with serum soluble fms-like tyrosine kinase-1:placental growth factor ratio (FPR, pg/pg) for preeclampsia (PE) prediction among unselected asymptomatic pregnant women in 2nd trimester. NCR and FPR were determined in 254 paired urine/blood samples collected simultaneously from 254 women at median gestational week (GW) 24 (range, 22–27) without hypertension or significant proteinuria in pregnancy (SPIP). Fifteen (5.9%) developed SPIP and hypertension at GW 34.0 (26.0–38.6) and 35.3 (27.6–38.6), respectively, and were diagnosed with PE at GW 35.7 (27.6–38.6). The 90th percentile level determined in 239 women normotensive throughout pregnancy gave NCR (139) sensitivity and positive predictive values (PPV) of 60% (9/15) and 27% (9/33), while those for serum FPR (4.85) were 40% (6/15) and 20% (6/30), respectively. Relative risks (95%CI) of later PE were 10.0 (3.82–26.4; 27% [9/33] vs. 2.7% [6/221]) and 4.98 (1.91–13.0; 20% [6/30] vs. 4.0% [9/224]) for NCR-positive and FPR-positive women, respectively. Cut-offs suggested by ROC gave NCR (86.6) sensitivity and PPV of 87% (13/15) and 17% (13/79), and FPR (8.8) values of 40% (6/15) and 40% (6/15), respectively. Thus, 2nd trimester NCR was superior to FPR for PE prediction.

Urinary nephrin—a potential marker of early glomerular injury: a systematic review and meta-analysis

“…Therefore, an important aspect to include in a meta-analysis such as this is the heterogeneity in diagnostic accuracy of the methods employed by the various studies. ELISA was the method of choice in most studies (n = 11) for the detection of nephrinuria in PE and nephropathies [20,24,25,31,32,36,43,45,[48][49][50]. Interestingly these assays demonstrated improved sensitivity (0.89) and specificity (0.73) and therefore diagnostic accuracy (AUC-SROC = 0.92) for determining urinary nephrin compared to RT-PCR [44,46,47].…”

“…An analysis of the 15 selected studies revealed that all studies aimed to investigate urinary nephrin as an early indicator of glomerular damage in both acute and chronic conditions. Eight studies utilised urinary nephrin for predicting PE [20,25,27,31,32,[43][44][45], six studies utilised urinary nephrin for predicting nephropathy [24,36,[46][47][48][49], and one study utilised urinary nephrin for predicting glomerulopathy/ glomerular injury [50]. Most of the studies used Enzyme Linked Immunosorbent Assay (ELISA) (n = 11) and the remaining used Real Time-Polymerase Chain Reaction (RT-PCR) (n = 3), and Western Blotting (WB) (n = 1) to determine the concentration of urinary nephrin.…”

Predictive Accuracy of Soluble FMS-Like Tyrosine Kinase-1/Placental Growth Factor Ratio for Preeclampsia in Japan: A Systematic Review

“…Thus, the ratio of sFlt-1 (i.e., anti-angiogenic factor) to PlGF (i.e., angiogenic factor) has been shown to increase before the onset of clinical signs and symptoms of PE. 6,[12][13][14][15][16][17] The sFlt-1/PlGF ratio is used as a tool to predict, diagnose, and manage PE in pregnant women suspected of having PE in several countries. [18][19][20][21] This test is now approved for use but is not yet routinely used in Japan.…”