Renal Dysfunction in Pre-eclampsia Patients: Prediction and Differential Diagnosis. Part 2

Abstract

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.