Analytical evaluation of the novel soluble fms-like tyrosine kinase 1 and placental growth factor assays for the diagnosis of preeclampsia.

OBJECTIVES: Performance evaluation of the novel BRAHMS KRYPTOR soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) assays.

DESIGN AND METHODS: Intra- and inter-assay imprecision, functional sensitivity, linearity in dilution, method comparison, and diagnostic capacity were evaluated.

RESULTS: Intra-assay coefficient of variations (CVs) were between 1.1% and 5.3% and inter-assay CVs between 3.9% and 11.1%. Functional sensitivity was 6.7ng/L for PlGF and 34ng/L for sFlt-1, respectively. The linearity in dilution was excellent (r>0.995) in the assay-specific relevant range of concentration. The KRYPTOR assay correlated well with the Elecsys sFlt-1 (r=0.996), Elecsys PlGF (r=0.990) and the Elecsys sFlt-1/PlGF ratio (r=0.947) with partially high mean bias values. The optimal cut points for diagnosis of preeclampsia were calculated for KRYPTOR assays at: 60.5ng/L (PlGF), 4725ng/L (sFlt-1), and 99.2 (sFlt-1/PlGF ratio) which were different with the corresponding Elecsys cut points. Nevertheless, the sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and areas under the curves (AUCs) were completely comparable in both assay platforms, even when applying the standard cut-off of 85 for sFlt-1/PlGF ratio or gestational age specific "rule in-rule-out" cut-offs for early and late onset preeclampsia.

CONCLUSION: The new BRAHMS KRYPTOR sFlt-1 and PlGF immunoassay show excellent precision and reliability. The assay results and the diagnostic capacity were highly comparable to established fully automated immunoassays (Elecsys). Hence, sFlt-1/PlGF ratio generated on KRYPTOR immunoassay platform should be suitable for diagnosing preeclampsia in clinical routine laboratory.