Plasma creatinine level increase is associated with creatinine tubular secretion increase that can be misinterpreted as elevated GFR in patients with moderate to severe decrease of corresponding levels (<50 ml/min). Non-linear correlation between plasma creatinine level and GFR values makes the detection of mild glomerular filtration disorders [20].
Padma Y. Et al studied typical changes of renal excretion disorders markers namely creatinine, uric acid and cystatine C in pregnant females. Serum levels of markers were established in samples taken in healthy females as well as in patients with hypertension, induced pregnancy and PE. In PE patients the levels of all three markers were significantly higher compared to control group of healthy patients; mean levels 1.47 ± 0.9 compared to 1.06 ± 0.2 for cystatine С, 0.95 ± 0.2 compared to 0.67 ± 0.1 for creatinine and 6.13 ± 1.8 compared to 4.28 ± 1.1 for uric acid respectively [21]. Apeksha Niraula reported normal creatinine levels in some patients with severe pre-eclampsy, with higher cystatine C levels corresponding to gestation terms [22]. Normal plasma creatinine level associated with elevated serum cystatine C level indicates pre-clinical stage of renal disease [23].
Grigorios Karampas et al studied serum NGAL level changes (s-NGAL) in healthy pregnant females and in females with PE. They reported significant increase of mean s-NGAL level in females with normal blood pressure reaching 12.8 during the first trimester, 25.9 during the third trimester (p = 0.002) and 48.0 (p<0.0001) during the third trimester. Significant increase of s-NGAL levels in patients with PE compared to patients with normal blood pressure has been reported during first (30.9; р = 0.006) and second (44.6; р = 0.015) trimesters [24]. Sun Min Kim et al reported significantly higher s-NGAL levels in patients with severe PE compared to patients with mild pre-eclampsy (237.5 ng/ml [67.4-575.4] compared to 125.9 ng/ml [66.1-295.7]) [25].
Nilgün Tekkeşin et al evaluated urine NGAL (uNGAL) level changes during normal pregnancy and in patients with PE. The authors reported significant level increase in patients with pre-eclampsy, with corresponding difference during various trimesters [26]. Unlike this, other studies reported uNGAL elevation in healthy pregnant patients, while no elevation has been detected in patients with pre-eclampsy. The authors consider uNGAL an insignificant early biomarker of pre-eclampsy [27,28].
Yuping Wang et al report similar uNGAL and KIM-1 (Kidney Injury Molecule-1) levels in patients with mild pre-eclampsy and in patients with normal blood pressure; however, significantly increased levels were reported in patients with severe pre-eclampsy. In patients with normal blood pressure urine KIM-1 level remained unchanged during pregnancy and within 6-8 weeks of post-partum period; in patients with severe pre-eclampsy higher KIM-1 levels were reported at pre-partum period, followed by significant decrease within 6-8 weeks. High urine KIM-1 level can also indicate pre-eclampsy associated renal ischemia. These studies indicate that urine KIM-1 can be a relatively sensitive biomarker of renal disorders associated with pre-eclampsy severity [29].
Therefore, pre-eclampsy mechanisms are based on multiple complex factors that require further investigation.
Despite numerous recent studies that have clarified the placenta-associated mechanism of pre-eclampsy, the methods for primary routine evaluation of pregnant patients are still not available. Several studies evaluating the effect of placenta size, shape and weight indicate the possible contribution of these factors to PE development. These results are promising for disease prognosis; however, further studies are required to figure out their use for early PE prediction.