Neutrophil gelatinase-associated lipocalin and Endothelin-1 as markers for the onset and severity of preeclampsia

  • Stephen Justice Adusu Department of Medical Diagnosis, School of Allied Health Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
  • Moses Banyeh Department of Biomedical Laboratory Science, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
  • Worlanyo Tashie Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences, University of Ghana, Legon, Ghana
  • Shafiat Omotoyosi Shittu Department of Population and Reproductive Health, School of Public Health, University for Development Studies, Tamale, Ghana
Keywords: Neutrophil gelatinase-associated lipocalin, Endothelin-1, Preeclampsia


Background: The onset of preeclampsia (PE) may be early (EOPE), or late (LOPE). Preeclampsia may also be characterized by severe features (PS) or without severe features (PNS). This study aimed to predict the onset and severity of PE using biomarkers including neutrophil gelatinase-associated lipocalin (sNGAL) and endothelin-1 (ET-1).
Method: This was a case-control study from January to June 2020. The study involved 270 pregnant women (control=135, PE=135), aged between 18-37 years. The cases and controls were matched by maternal and gestational age at sampling. Serum samples were assayed for sNGAL and ET-1 using the ELISA technique.
Results: Serum NGAL and ET-1 were significantly increased in PE and also increased in PE characterized by severe features (P<0.010). Both sNGAL and ET-1 positively correlated with blood pressure in PE (P<0.050). In predicting PE, the area under the curve, sensitivity and specificity of sNGAL were 0.76, 46.2% and 97.8% while that of ET-1 were 0.82, 66.8%, and 92.5% respectively. Also, ET-1 could differentiate PS from PNS with a sensitivity of 85.7% and specificity of 82.1%.
Conclusion: Serum ET-1 is better than sNGAL in the prediction of PE. We recommend screening pregnant women using ET-1 for the early detection and management of PE.

Annals of Medical Laboratory Science (2022) 2(1), 23 - 34


ACOG. (2019). ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol, 133(1), 1. doi:10.1097/ aog.0000000000003018

Aggarwal, P., Chandel, N., Jain, V., & Jha, V. (2012). The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia. Journal of human hypertension, 26(4), 236-241.

Ajne, G., Ahlborg, G., Wolff, K., & Nisell, H. (2005). Contribution of endogenous endothelin-1 to basal vascular tone during normal pregnancy and preeclampsia. American journal of obstetrics and gynecology, 193(1), 234-240.

Ajne, G., Wolff, K., Fyhrquist, F., Carlström, K., Hemsén‐Mörtberg, A., & Nisell, H. (2003). Endothelin converting enzyme (ECE) activity in normal pregnancy and preeclampsia. Hypertension in pregnancy, 22(3), 215-224.

Akbas, M., & Koyuncu, F. M. (2020). Evaluation of maternal renal cortical elasticity in pregnancies with early- and late-onset preeclampsia. J Matern Fetal Neonatal Med, 33(8), 1434-1440. doi:10.1080/14767058.2019.1671347

Alese, M. O., Moodley, J., & Naicker, T. (2021). Preeclampsia and HELLP syndrome, the role of the liver. The Journal of Maternal-Fetal & Neonatal Medicine, 34(1), 117-123.

Alexander, B. T., Kassab, S. E., Miller, M. T., Abram, S. R., Reckelhoff, J. F., Bennett, W. A., & Granger, J. P. (2001). Reduced uterine perfusion pressure during pregnancy in the rat is associated with increases in arterial pressure and changes in renal nitric oxide. Hypertension, 37(4), 1191-1195.

Artunc-Ulkumen, B., Guvenc, Y., Goker, A., & Gozukara, C. (2015). Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia. J Matern Fetal Neonatal Med, 28(16), 1895-1900. doi:10.3109/14767058.2014.972926

Atiba, A. S., Abbiyesuku, F. M., Oparinde, D. P., Niran-Atiba, T. A., & Akindele, R. A. (2016). Plasma Malondialdehyde (MDA): An Indication of Liver Damage in Women with Pre-Eclamsia. Ethiop J Health Sci, 26(5), 479-486. doi:10.4314/ejhs.v26i5.10

Baksu, B., Davas, I., Baksu, A., Akyol, A., & Gulbaba, G. (2005). Plasma nitric oxide, endothelin-1 and urinary nitric oxide and cyclic guanosine monophosphate levels in hypertensive pregnant women. International Journal of Gynecology & Obstetrics, 90(2), 112-117.

Coffey, C. G. (2019). Issues in the interpretation of serum endothelin levels in preeclampsia. Medical hypotheses, 133, 109400.

Cui, L., Shu, C., Liu, Z., Tong, W., Cui, M., Wei, C.,. . . Li, Y. (2018). Serum protein marker panel for predicting preeclampsia. Pregnancy Hypertens, 14, 279-285. doi:10.1016/j.preghy.2018.01.009

Cui, Y., Wang, W., Dong, N., Lou, J., Srinivasan, D. K., Cheng, W., . . . Peng, J. (2012). Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy. Nature, 484(7393), 246-250.

D'anna, R., Baviera, G., Giordano, D., Russo, S., & Dugo, N. (2009). First trimester serum PAPP-A and NGAL in the prediction of late-onset pre-eclampsia. Prenat Diagn, 29 (11), 1066-1068.

D'Anna, R., Baviera, G., Giordano, D., Todarello, G., Corrado, F., & Buemi, M. (2008). Second trimester neutrophil gelatinaseassociated lipocalin as a potential prediagnostic marker of preeclampsia. Acta obstetricia et gynecologica Scandinavica, 87(12), 1370-1373.

D'Anna, R., Baviera, G., Giordano, D., Todarello, G., Russo, S., Recupero, S., Corrado, F. (2010). Neutrophil gelatinase-associated lipocalin serum evaluation through normal pregnancy and in pregnancies complicated by preeclampsia. Acta obstetricia et gynecologica Scandinavica, 89(2), 275-278.

Faxén, M., Nasiell, J., Lunell, N.-O., & Blanch, A. (1997). Differences in mRIMA expression of endothelin-1, c-fos and c-jun in placentas from normal pregnancies and pregnancies complicated with preeclampsia and/or intrauterine growth retardation. Gynecologic and obstetric investigation, 44(2), 93-96.

George, E. M., & Granger, J. P. (2011). Endothelin: key mediator of hypertension in preeclampsia. American journal of hypertension, 24(9), 964-969.

George, E. M., Palei, A. C., & Granger, J. P. (2012). Endothelin as a final common pathway in the pathophysiology of preeclampsia: therapeutic implications. Current opinion in nephrology and hypertension, 21(2), 157.

Ives, C. W., Sinkey, R., Rajapreyar, I., Tita, A. T. N., & Oparil, S. (2020). Preeclampsia-Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review. J Am Coll Cardiol, 76(14), 1690-1702. doi:10.1016/j.jacc.2020.08.014

Jiang, L., Zhou, Y., & Huang, Q. (2021). Serum fibroblast growth factor 21 level is increased in pre‐eclampsia patients: Association with blood pressure and lipid profile. Journal of Obstetrics and Gynaecology Research, 47(1), 375-381.

Karampas, G., Eleftheriades, M., Panoulis, K., Rizou, M., Haliassos, A., Hassiakos, D.,. Rizos, D. (2014). Maternal serum levels of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study. Prenat Diagn, 34(8), 726-733. doi:10.1002/pd.4337

Kim, S. M., Park, J. S., Norwitz, E. R., Jung, H. J., Kim, B. J., Park, C. W., & Jun, J. K. (2013). Circulating levels of neutrophil gelatinaseassociated lipocalin (NGAL) correlate with the presence and severity of preeclampsia. R e p r o d S c i , 2 0 ( 9 ) , 1 0 8 3 - 1 0 8 9 . doi:10.1177/1933719113477480

Lugobe, H. M., Muhindo, R., Kayondo, M., Wilkinson, I., Agaba, D. C., McEniery, C., Boatin, A. A. (2020). Risks of adverse perinatal and maternal outcomes among women with hypertensive disorders of pregnancy in southwestern Uganda. PLoS One, 15(10), e0241207. doi:10.1371/journal.pone.0241207

Makris, A., Thornton, C., Thompson, J., Thomson, S., Martin, R., Ogle, R., . . . Hennessy, A. (2007). Uteroplacental ischemia results in proteinuric hypertension and elevated sFLT-1. Kidney Int, 71(10), 977-984.

Nabweyambo, S., Sande, O. J., McGovern, N., Bwanga, F., Ssekagiri, A., Keesiga, A., Nakimuli, A. (2021). Circulating levels of angiogenic factors and their association with preeclampsia among pregnant women at Mulago National Referral Hospital in Uganda. PLoS One, 16(5), e0251227.doi:10.1371/journal.pone.0251227

Napolitano, M., Miceli, F., Calce, A., Vacca, A., Gulino, A., Apa, R., & Lanzone, A. (2000). Expression and relationship between endothelin-1 messenger ribonucleic acid (mRNA) and inducible/endothelial nitric oxide synthase mRNA isoforms from normal and preeclamptic placentas. The Journal of Clinical Endocrinology & Metabolism, 85(6), 2318-2323.

Nishikawa, S., Miyamoto, A., Yamamoto, H., Ohshika, H., & Kudo, R. (2000). The relationship between serum nitrate and endothelin-1 concentrations in preeclampsia. Life sciences, 67(12), 1447-1454.

Patel, M., Sachan, R., Gangwar, R., Sachan, P., & Natu, S. (2013). Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy. Int J Nephrol Renovasc Dis, 6, 181-186. doi:10.2147/ijnrd.s45523

Rana, S., Lemoine, E., Granger, J. P., & Karumanchi, S. A. (2019). Preeclampsia: pathophysiology, challenges, and perspectives. Circulation research, 124(7), 1094-1112.

Sachan, R., Patel, M., Gaurav, A., Gangwar, R., & Sachan, P. (2014). Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy. Adv Biomed Res, 3, 223. doi:10.4103/2277-9175.145690

Saleh, L., Danser, J. A., & van den Meiracker, A. H. (2016). Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment. Current opinion in nephrology and hypertension, 25(2), 94-99.

Saleh, L., Verdonk, K., Visser, W., van den Meiracker, A. H., & Danser, A. H. (2016). The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia. Ther Adv Cardiovasc Dis, 10 (5), 282-293. doi:10.1177/1753944715624853

Sani, H. M., Vahed, S. Z., & Ardalan, M. (2019). Preeclampsia: a close look at renal dysfunction. Biomedicine & Pharmacotherapy, 109, 408-416.

Scazzochio, E., Munmany, M., Garcia, L., Meler, E., Crispi, F., Gratacos, E., & Figueras, F. (2014). Prognostic role of maternal neutrophil gelatinase-associated lipocalin in women with severe early-onset preeclampsia. Fetal Diagn Ther, 35(2), 127-132. doi:10.1159/000356499

Simonazzi, G., Capelli, I., Curti, A., Comai, G., Rizzo, N., & La Manna, G. (2015). Serum and Urinary Neutrophil Gelatinaseassociated Lipocalin Monitoring in Normal Pregnancy Versus Pregnancies Complicated by Pre-eclampsia. In Vivo, 29(1), 117-121.

Sorohan, B. M., Andronesi, A., Ismail, G., Jurubita, R., Obrisca, B., Baston, C., & Harza, M. (2020). Clinical Predictors of Preeclampsia in Pregnant Women with Chronic Kidney Disease. Medicina (Kaunas), 56(5). doi:10.3390/medicina56050213

Taylor, R. N., Varma, M., Teng, N. N., & Roberts, J. M. (1990). Women with preeclampsia have higher plasma endothelin levels than women with normal pregnancies. The Journal of Clinical Endocrinology & Metabolism, 71(6), 1675-1677.

Verdonk, K., Saleh, L., Lankhorst, S., Smilde, J. I., Van Ingen, M. M., Garrelds, I. M., Visser, W. (2015). Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin–angiotensin–aldosterone system suppression. Hypertension, 65(6), 1316-1323.

Von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gøtzsche, P. C., Vandenbroucke, J. P., & Initiative, S. (2014). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. International journal of surgery, 12(12), 1495-1499.

Wantania, J., Wijaya, Y., Lumentut, A., Wantania, F., Harman, B., Kepel, B., & Limono, F. (2021). The Correlation of the Lipid Profile and Endothelin-1 with Severe Preeclampsia. Asian Research Journal of Gynaecology and Obstetrics, 7-16.

Wiles, K., Chappell, L. C., Lightstone, L., & Bramham, K. (2020). Updates in Diagnosis and Management of Preeclampsia in Women with CKD. Clin J Am Soc Nephrol, 15(9), 1371-1380. doi:10.2215/cjn.15121219
How to Cite
Adusu, S. J., Banyeh, M., Tashie, W., & Shittu, S. O. (2022). Neutrophil gelatinase-associated lipocalin and Endothelin-1 as markers for the onset and severity of preeclampsia. Annals of Medical Laboratory Science, 2(1), 23-34.

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