THE AIM: To assess the significance of prognostic markers of preeclampsia – sFlt-1 and PlGF in the differential diagnosis of preeclampsia and chronic kidney disease.PATIENTS AND METHODS:patients whom signed informed consent, was taken samples of blood in the third trimester of pregnancy. The study group included 36 patients with preeclampsia, the comparison group of 46 pregnant women with CKD and the control group included 40 healthy patients, with pregnancy without complication.RESULTS: Significant differences in the levels of serum sFlt-1 and PlGF were found: between the PE and the comparison group (CKD), as well as between the PE and the control group (CG), whereas no differences were found between the CG and CKD. The sFlt-1 level was significantly increased in PE compared with CKD and KG (5.12-fold and 4.25-fold higher, respectively). Serum PlGF levels were significantly reduced in PE relative to both CKD and KG (17.4 and 12.5 times lower, respectively). The sFlt-1/PlGF ratio was significantly increased in PE compared with CKD and the control group (approximately 25 times higher in both groups), but there was no significant difference between CKD and CG.CONCLUSION:Thus, the definition of the relationship sFlt-1, PlGF, sFlt-1/PlGF can be used in the differential diagnosis of preeclampsia and chronic kidney disease.
Study Objective: To assess the prognostic value, sensitivity, and specificity of biomarkers of acute renal injury (ARI), and of angiogenic factors, in the development of pre-eclampsia (PE) in the second trimester of pregnancy, and determine their diagnostic significance for PE, as well as to compare obstetric and perinatal outcomes experienced by patients. Study Design: This was a comparative, group, prospective and retrospective study. Materials and Methods: The patient groups studied in the first, second, and third phases are described in Part 1 of this article. Based on the distinguishing diagnostic criterion and the outcomes of pregnancy, the 138 patients were divided into three groups. Group I (main) consisted of 66 (47.8%) patients who developed hypertensive disorders during pregnancy, 30 (21.7%) of whom were included in subgroup 1 (CKD) and 36 (26.1%) in subgroup 2 (no CKD). Group II (comparison) was made up of 32 patients with CKD who did not have hypertensive disorders. Group III (control) comprised 40 women with normal pregnancies and no history of reproductive disorders. The fourth phase involved a retrospective analysis of biomarker levels and assessment of their prognostic value for the development of PE. All participants underwent clinical and laboratory examinations and had measurements taken for sFlt-1, PlGF, S-endoglin, cystatin C, uKIM-1, podocalyxin, and α1- and β2-microglobulins. Obstetric and perinatal outcomes were traced. Study Results: Levels of the following parameters had the greatest prognostic value in the second trimester of pregnancy: PlGF (94%), sFlt-1 (92%), sFlt-1/PlGF (94%), ΔPlGF (93.3%), ΔsFlt-1 (92%), ΔsFlt-1/PlGF (94%), S-endoglin (94%), and sNGAL (94%). The sensitivity of the sFlt-1/PlGF ratio at this stage of pregnancy was 89.1%, making this parameter a promising predictive marker of PE. Logistic regression analysis showed that it is most reasonable to measure sFlt-1/PlGF and sNGAL levels in the first trimester; and in the second trimester, ΔsFlt-1/PlGF (between the first and second trimesters) and sFlt-1/PlGF as well as levels of PlGF, S-endoglin, uKIM-1, urinary podocalyxin, and sNGAL. In both subgroups of patients with PE, there were critical hemodynamic disruptions in the fetal-placental-maternal system: six (20%) and eight (22.2%) cases in subgroups 1 and 2, respectively. Pre-term delivery in patients with pre-existing intrauterine growth retardation led to the necessity of putting 22 (73.3%) newborns from the first subgroup and seven (19.4%) newborns from the second subgroup on mechanical ventilation (p<0.0001). Conclusion: Some weeks before the clinical onset of PE, at weeks 16-24 of pregnancy, patients develop placental dysfunction, decreases or slight increases in PlGF levels, and elevation of sFlt-1 levels, reflecting an imbalance between pro-angiogenic and anti-angiogenic factors; there is also an increase in the levels of markers of ARI (sNGAL, uKIM-1, β2- and α1-microglobulins, and urinary podocalyxin). The clinical information obtained about perinatal outcomes indirectly confirms the role of the cascade of pathogenic events in chronic placental insufficiency, in the development of generalized endothelial dysfunction. Keywords: pre-eclampsia, predictive diagnosis, chronic kidney disease, sFlt-1, PlGF, S-endoglin, cystatin C, KIM-1, podocalyxin, α1-microglobulin, β2-microglobulin.
Цель исследования: оценить прогностическую значимость, чувствительность и специфичность биомаркеров острого повреждения почек (ОПП) и ангиогенных факторов в развитии преэклампсии (ПЭ), а также определить их значение в патогенезе ранней и поздней формы ПЭ для ее дифференциальной диагностики с изолированной почечной дисфункцией. Дизайн: сравнительное групповое проспективное исследование. Материалы и методы. В первый этап исследования включили 122 беременных, из них у 46 (37,7%) имелась хроническая болезнь почек (ХБП). Целью второго этапа исследования стал поиск дифференциально-диагностического критерия ХБП и ПЭ. Из 122 пациенток у 36 зафиксирована ПЭ. В третий этап включили еще 16 беременных с ХБП. На основании дифференциально-диагностического критерия и исходов беременности 138 пациенток разделили на три группы, причем 14 женщин из группы сравнения были переведены в основную группу: I группа (основная) -66 (47,8%) пациенток с развитием гипертензивных расстройств при беременности (1-я подгруппа -30 (21,7%) женщин с ХБП, 2-я подгруппа -36 (26,1%) пациенток без ХБП); II группа (сравнения) -32 пациентки с ХБП без гипертензивных расстройств; III группа (контрольная) -40 женщин с физиологическим течением данной беременности и неосложненным репродуктивным анамнезом. Проведено клинико-лабораторное обследование всех участниц, у них измерены уровни sFlt-1, PlGF, S-эндоглина, цистатина С, KIM-1, подокаликсина, α1и β2-микроглобулина. Результаты. Анализ ROC-кривой показал, что пороговая концентрация sFlt-1 для отличия ПЭ от ХБП -7715 пг/мл (чувствительность -97%, специфичность -96%), а PlGF -88,15 пг/мл (чувствительность -90%, специфичность -100%), пороговое значение отношения sFlt-1/ PlGF -150,25 (чувствительность -100%, специфичность -100%). Наибольшей чувствительностью и специфич ностью обладает метод определения отношения sFlt-1/PlGF при максимальной точности (94%) и значимости отрицательного прогностического значения (95,4%). Заключение. Значение sFlt-1/PlGF ≥ 150,25 может быть дифференциально-диагностическим критерием ПЭ пациенток с артериальной гипертензией и клинически значимой протеинурией. Мы предполагаем, что использование выявленного нами диф ференциальнодиагностического критерия (определение содержания изучаемых маркеров в периферической крови и моче) могут быть эффективными как для диагностики уже развившейся ПЭ, так и для прогноза ее возникновения.
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