A PEER-REVIEWED JOURNAL OF RESEARCH AND CLINICAL MEDICINEISSN 1727-2378 (Print)         ISSN 2713-2994 (Online)
Ru
En

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

DOI:10.31550/1727-2378-2020-19-8-7-13
For citation: Bezhenar V.F., Smirnov A.V., Temirbulatov R.R., Gabelova K.A., Shapkaits V.A., Nesterov I.M. Renal Dysfunction in Pre-eclampsia Patients: Prediction and Differential Diagnosis. Part 2. Doctor.Ru. 2020; 19(8): 7–13. (in Russian). DOI: 10.31550/1727-2378-2020-19-8-7-13

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.

Contributions: Dr. V.F. Bezhenar and Dr. A.V. Smirnov designed the study and approved the final version of the manuscript submitted for publication. Dr. R.R. Temirbulatov and Dr. K.A. Gabelova collected clinical material, followed up patients during pregnancy, and did statistical analysis of study data. Dr. V.A. Shapkaits and Dr. I.M. Nesterov collected clinical material and described the study groups. 

Conflict of interest: The authors declare that they do not have any conflict of interests

Part 1 of this article was published in Doctor.Ru Gynecology. Vol. 19, No. 8 (2020), pp. 23–29

V.F. Bezhenar (Corresponding author) — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Federation Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: bez-vitaly@yandex.ru

A.V. Smirnov — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Federation Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: smirnov@nephrolog.ru

R.R. Temirbulatov — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Federation Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: rinattmr@gmail.com

K.A. Gabelova — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Federation Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: kgabelova@mail.ru

V.A. Shapkaits — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Federation Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. Maternity Hospital No. 16 (a Government-funded Healthcare Institution of St. Petersburg); 54A Malaya Balkanskaya St., St. Petersburg, Russian Federation 192283. E-mail: shapkaitz@mail.ru

I.M. Nesterov — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Federation Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: ignester@yandex.ru

Доктор.ру

Table 1

Serum concentrations of biomarkers at weeks 16-24 of pregnancy, Me (25th percentile, 75th percentile)

t1_1-1.jpg t1_1-2.jpg

Fig. 1. ROC curve: angiogenic factors (2nd trimester of pregnancy)

r1_1.jpg

Fig. 2. ROC curve: markers of acute renal injury (2nd trimester of pregnancy)

r1_2.jpg

Table 2

Concentrations of predictive biomarkers of pre-eclampsia: Logistic regression analysis

t1_2.jpg
 

Received: 16.03.2020

Accepted: 04.06.2020

LITERATURE
  1. Medvedev B.I., Syundyukova E.G., Sashenkov S.L. Ways to prevent pre-eclampsia. Modern Problems of Science and Education. 2017; 2. (in Russian). URL: http://www.science-education.ru/ru/article/ view?id=26296 (Accessed January 14, 2020)
  2. Gunnarsson R., Åkerström B., Hansson S.R., Gram M. Recombinant alpha-1-microglobulin: a potential treatment for preeclampsia. Drug Discov. Today. 2017; 22(4): 736–43. DOI: 10.1016/j.drudis.2016.12.005
  3. Spradley F.T., Tan A.Y., Joo W.S. et al. Placental growth factor administration abolishes placental ischemia-indused hypertension. Hypertension. 2016; 67(4): 740–7. DOI: 10.1161/HYPERTENSIONAHA. 115.06783
  4. Akolekar R., Syngelaki A., Sarquis R. et al. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11–13 weeks. Prenat. Diagn. 2011; 31(1): 66–74. DOI: 10.1002/pd.2660
  5. Odibo A.O., Zhong Y., Goetzinger K.R. et al. First-trimester placental protein 13, PAPP-A, uterine artery Doppler and maternal characteristics in the prediction of pre-eclampsia. Placenta. 2011; 32(8): 598–602. DOI: 10.1016/j.placenta.2011.05.006
  6. Cunningham F.G., Leveno K.J., Bloom S.L. et al., eds. Williams Obstetrics. N.Y.: McGraw Hill; 2014. 1376 p.
  7. Audibert F., Boucoiran I., An N. et al. Screening for preeclampsia using first-trimester serum markers and uterine artery Doppler in nulliparous women. Am. J. Obstet. Gynecol. 2010; 203(4): 383.e1–8. DOI: 10.1016/j.ajog.2010.06.014
  8. Mei-Dan E., Wiznitzer A., Sergienko R. et al. Prediction of preeclampsia: liver function tests during the first 20 gestational weeks. J. Matern. Fetal Neonatal Med. 2013; 26(3): 250–3. DOI: 10.3109/14767058.2012.733771
  9. Sidorova I.S., Filippov O.S., Nikitina N.A. et al. Causes of maternal mortality associated with pre-eclampsia and eclampsia in Russia in 2013. Obstetrics and Gynecology. 2015; 4: 11–18. (in Russian)
  10. Khodzhaeva Z.S., Kholin A.M., Vikhlyaeva E.M. Early and late pre-eclampsia: paradigms of pathological biology and clinical practice. Obstetrics and Gynecology. 2013; 10: 4–11. (in Russian)
  11. Savelieva G.M., Sukhikh G.T., Serov V.N. et al., eds. Obstetrics: national guide. M.: GEOTAR-Media; 2015. 1088 p. (in Russian)
  12. Taylor R., Roberts J., Cunningham F. et al. Chesley’s hypertensive disorders in pregnancy. Amsterdam: Academic Press; 2014. 484 p.
  13. Andersgaard A.B., Acharya G., Mathiesen E.B. et al. Recurrence and long-term maternal health risks of hypertensive disorders of pregnancy: a population-based study. Am. J. Obstet. Gynecol. 2012; 206(2): 143.e1–8. DOI: 10.1016/j.ajog.2011.09.032
  14. Temirbulatov R.R., Bezhenar V.F., Smirnov A.V. Differential diagnostics of preeclampsia in patients with chronic kidney disease. Nephrology. 2019; 23(1): 45–50. (in Russian). DOI: 10.24884/1561-6274-2019-23-1-45-50
  15. Ailamazyan E.K., Mozgovaya E.V. Pre-eclampsia: theory and practice M.: MEDpress-Inform; 2008. 272 p. (in Russian)

News

30 June 00:00
A New Issue of Doctor.Ru Neurology Psychiatry, Vol. 20, No. 5 (2021), Published

Find original articles and reviews covering various aspects of neurology, psychiatry and the interview with Professor Marina Arkadievna Kinkulkina

28 June 00:00
A New Issue of Doctor.Ru Internal Medicine, Vol. 20, No. 4 (2021), Published

Find original articles and reviews covering various aspects of cardiology, gastroenterology, internal medicine and the interview with Professor Elena Zelikovna Golukhova

 

3 May 17:06
A New Issue of Doctor.Ru Pediatrics, Vol. 20, No. 3 (2021), Published

Find original articles and reviews covering various aspects of pediatrics and the interview with Professor Evgeny Grigorievich Furman

3 May 17:06
A New Issue of Doctor.Ru Endocrinology, Vol. 20, No. 2 (2021), Published

Find original articles and reviews covering various aspects of endocrinology and the interview with Professor Valentin Viktorovich Fadeev

16 April 11:57
Igor Evgenievich Khatkov joined the American Surgical Association

Igor Evgenievich Khatkov, Head of A. S. Loginov Moscow Clinical Scientific and Practical Centre, Chief Oncologist in and for Moscow is now an honoured member of the American Surgical Association.

All news