Pregnancy in women with primary chronic glomerulonephritis in the era of prevention of placenta-associated complications. A review and analysis of outcomes of 120 pregnancies in one center

Aim: To determine the pregnancy complications and outcomes in patients with primary chronic glomerulonephritis (CGN) in the era of placenta-associated complications prevention. Methods: 120 pregnancies in 114 women with CGN and chronic kidney disease (CKD) grades 1-4 were included; 20 pregnancies in 20 healthy women were considered as the control group. All women with CGN received antiplatelet agents to prevent preeclampsia (PE); in the presence of additional risk factors, heparin was prescribed. Results: A favorable pregnancy outcome in CGN was observed in 94.2% cases. In patient with CGN, compared healthy women, PE was more often: in 25.2% versus 0.0%, p=0.013; placental insufficiency in 28.3% versus 0.0%, p=0.004; urinary tract infection in 19.2% versus 0.0%, p=0.044; cesarean section (CS) in 33.9% versus 10.0%, p=0.036. The body weight of newborns in CGN group was significantly lower comparing control: 3100 [Q1-Q3: 2800; 3485] g versus 3355 [Q1-Q3: 3200; 3710] g, p=0.015. The incidence of PE, fetal growth retardation, preterm delivery, CS, treatment of newborns in ICU was highest in patients with CKD G3 and G4: 35% (G3) and 66.7% (G4), 50% and 100%, 45% and 100%, 70% and 100%, 31.6% and 100%, respectively. The complication frequency depended on baseline proteinuria more than 1g/day (PU) and arterial hypertension (AH). Frequency of PE in women without PU/without AH was 7%, with AH without PU - 37.5%, with PU without AH - 44%, with PU and AH - 50%, p=0.0002; preterm delivery - 3.5%, 15.8%, 22.2%, 45.5%, respectively, p=0.0013; treatment of babies in ICU - 1.8%, 5.3%, 11.1%, 45.5%, respectively, p<0.0001. Independent risk factors for preterm delivery were CRF in mother - RR 16.182 [95%CI 4.669-56.081], p<0.0001; placental insufficiency - RR 4.750 [95%CI 1.534-14.709], p=0.011; the absence of severe PE was a protective factor: OR 0.115 [95%CI 0.069-0.192], p=0.016. Nine out of 114 (7.9%) patients with CGN reached CKD G5 32.3 [Q1-Q3: 21.1; 50.0] months postpartum. Conclusion: We observed a high incidence of favorable pregnancy outcomes in women with CGN. Most the unfavorable outcomes were due to PE and placental insufficiency. Preconception care and prevention of placenta-associated complications can improve gestational outcomes in patients with CGN.

pregnancy, chronic glomerulonephritis, chronic kidney disease, pregnancy outcomes, preeclampsia prevention

1. Gleeson S., Lightstone L. Glomerular disease and pregnancy.Adv Chronic Kidney Dis. 2020; 27(6):469-476. DOI: 10.1053/j.ackd.2020.08.001. 10.1053/j.ajkd.2008.11.034

2. Madej A., Mazanowska N., Cyganek A. et al. Neonatal and maternal outcomes among women with glomerulonephritis. Am J Nephrol. 2020;51(7):534-541. DOI: 10.1159/000508600

3. Григорьева Е.В., Карпова О.Г., Патрикеева Д.А. Патология почек при беременности (по данным нефрологического отделения ОКБ г. Саратова). Тезисы XIII международной школы-семинара под эгидой ISN "Неделя нефрологии в Москве 2013" и VIII Всероссийской научно-практической Конференции РДО (20-24 ноября 2013, Москва). Нефрология и диализ. 2013; 15 (4):311.

4. Cabiddu G., Castellino S., Gernone G. et al. A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy. J Nephrol. 2016; 29:277-303. DOI: 10.1007/s40620-016-0285-6

5. Blom K., Odutayo A., Bramham K., Hladunewich M.A. Pregnancy and glomerular disease: a systematic review of the literature with management guidelines. Clin J Am Soc Nephrol. 2017;12(11):1862-1872. DOI: 10.2215/CJN.00130117

6. Shimizu A., Takei T., Moriyama T. et al. Effect of kidney disease stage on pregnancy and delivery outcomes among patients with immunoglobulin A nephropathy. Am J Nephrol. 2010; 32:456-461. DOI: 10.1159/000320730

7. Limardo M., Imbasciati E., Ravani P. et al. Pregnancy and progression of IgA nephropathy: results of an Italian multicenter study. Am J Kidney Dis. 2010; 56:506-512. DOI: 10.1053/j.ajkd.2010.03.033

8. Wang F., Lu J.-D., Zhu Y. et al. Renal outcomes of pregnant patients with immunoglobulin A nephropathy: a systematic review and meta-analysis. Am J Nephrol. 2019;49(3):214-224. DOI: 10.1159/000496410

9. Surian M., Imbasciati E., Cosci P. et al. Glomerular disease and pregnancy. A study of 123 pregnancies in patients with primary and secondary glomerular diseases. Nephron. 1984; 36: 101-105. DOI: 10.1159/000183126

10. Barceló P., López-Lillo J., Cabero L., Del Río G. Successful pregnancy in primary glomerular disease. Kidney Int. 1986; 30: 914-919. DOI: 10.1038/ki.1986.272

11. Garovic V.D. The role of the podocyte in preeclampsia. Clin J Am Soc Nephrol. 2014 Aug 7; 9(8): 1337-1340. DOI: 10.2215/CJN.05940614

12. Lioufas N., Ling J., Jaw J. et al. Does pre-eclampsia predispose patients to the development of focal segmental glomerulosclerosis? "The Chicken or the Egg?". J Clin Nephrol Ren Care. 2016; 2:012. DOI: 10.23937/2572-3286.1510012

13. Lo J.O., Kerns E., Rueda J., Marshall N.E. Minimal change disease in pregnancy. J Matern Fetal Neonatal Med. 2014; 27(12):1282-1284. DOI: 10.3109/14767058.2013.852178

14. Sato H., Asami Y., Shiro R. et al. Steroid pulse therapy for de novo minimal change disease during pregnancy. Am J Case Rep. 2017; 18: 418-421. DOI: 10.12659/ajcr.902910

15. Gleeson S., Cardoso F., Lightstone L. et al. A new approach to de novo minimal change disease in pregnancy. Nephrology (Carlton). 2021 Mar 16. DOI: 10.1111/nep.13871

16. Liu Z., Cui Z., He Y. et al. Membranous nephropathy in pregnancy. Am J Nephrol. 2020;51:304-317. DOI: 10.1159/000505175

17. Irish G.L., Jesudason S. Case study of tacrolimus as an effective treatment for idiopathic membranous glomerulonephritis in pregnancy. Obstet Med. 2020;13(3):148-150. DOI: 10.1177/1753495X18816923

18. Zanchelli F., Isola E., Cicciarella L. et al. Minimal change relapse during pregnancy. G Ital Nefrol. 2018 Jul;35(4):2018-vol4.

19. Orozco Guillén O.A., Velazquez Silva R.I., Gonzalez B.M. et al. Collapsing lesions and focal segmental glomerulosclerosis in pregnancy: a report of 3 cases. Am J Kidney Dis. 2019;74(6):837-843. DOI: 10.1053/j.ajkd.2019.04.026

20. Wiles K., Chappell L., Clark K. et al. Clinical practice guideline on pregnancy and renal disease. BMC Nephrology. 2019; 20:401. DOI:10.1186/s12882-019-1560-2

21. Thomas A.G., Burrows L., Knight R. et al. The effect of pregnancy on cyclosporine levels in renal allograft patients. Obstet Gynecol. 1997;90(6):916-919. DOI: 10.1016/s0029-7844(97)00535-8

22. Zheng S., Easterling T.R., Umans J.G. et al. Pharmacokinetics of tacrolimus during pregnancy. Ther Drug Monit. 2012; 34:660-670. DOI: 10.1097/FTD.0b013 e3182 708ed f

23. Рогов В.А., Шилов Е.М., Козловская Н.Л. и соавт. Хронический гломерулонефрит и беременность. Тер. архив. 2004; 76(9): 21-25.

24. Zhang J.J., Ma X.X., Hao L. et al. A systematic review and meta-analysis of outcomes of pregnancy in CKD and CKD outcomes in pregnancy. Clin J Am Soc Nephrol. 2015;10(11):1964-1978. DOI: 10.2215/CJN.09250914

25. Беспалова А.В., Козловская Н.Л., Коротчаева Ю.В., Бондаренко Т.В. Плацентарные факторы ангиогенеза и дифференциальная диагностика при массивной протеинурии у беременных. Клиническое наблюдение и обзор литературы. Нефрология и диализ. 2016;18 (4):431-439.

26. Chappell L.C., Duckworth S., Seed P.T. et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013; 128: 2121-2131. DOI: 10.1161/CIRCULATIONAHA.113.003215

27. Agrawal S., Cerdeira A.S., Redman C. et al. Meta-analysis and systematic review to assess the role of soluble fms-like tyrosine kinase-1 and placenta growth factor ratio in prediction of preeclampsia. Hypertension. 2018; 71: 306-316. DOI: 10.1161/HYPERTENSIONAHA.117.10182

28. Rolfo A., Attini R., Tavassoli E. et al. Is it possible to differentiate chronic kidney disease and preeclampsia by means of new and old biomarkers? A prospective study. Dis Markers. 2015; 2015:127083. DOI: 10.1155/2015/127083

29. Bramham K., Seed P.T., Lightstone L. et al. Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and chronic kidney disease. Kidney Int. 2016; 89: 874-885. DOI: 10.1016/j.kint.2015.10.012

30. Никольская И.Г., Прокопенко Е.И., Ватазин А.В., Будыкина Т.С. Ангиогенные и антиангиогенные факторы у беременных с хронической болезнью почек: роль коэффициента SFlt-1/PlGF в прогнозировании и диагностике преэклампсии. Нефрология и диализ. 2016; 18(4): 440-451.

31. Roberge S., Villa P., Nicolaides K. et al. Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther. 2012;31(3):141-146. DOI: 10.1159/000336662

32. Roberge S., Gigue`re Y., Villa P. et al. Early administration of low-dose aspirin for the prevention of severe and mild preeclampsia: a systematic review and meta-analysis. Am J Perinatol. 2012; 29(7): 551-556. DOI: 10.1055/s-0032-1310527

33. Wang M., Chen S., He Y. et al. Low-dose aspirin for the prevention of severe preeclampsia in patients with chronic kidney disease: a retrospective study: This is the study for kidney and pregnancy. J Nephrol. 2021 Apr 29. DOI: 10.1007/s40620-021-01049-3.

34. Прокопенко Е.И., Никольская И.Г., Ватазин А.В. и соавт. Влияние гепарина и антиагрегантов на исход беременности у женщин с хронической почечной недостаточностью. Нефрология и диализ. 2015; 17(2): 185-192.

35. Cruz-Lemini M., Va´zquez J.C., Ullmo J., Llurba E. Low-molecular-weight heparin for prevention of preeclampsia and other placenta-mediated complications: a systematic review and meta-analysis. Am J Obstet Gynecol. Published: April 19, 2021. DOI: 10.1016/j.ajog.2020.11.006

36. Magee L.A., von Dadelszen P., Rey E. et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372(5):407-417. DOI: 10.1056/NEJMoa1404595

37. Abalos E., Duley L., Steyn D.W. et al. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2018;10(10):CD002252. DOI: 10.1002/14651858.CD002252.pub4

38. Vasilakis-Scaramozza C., Aschengrau A., Cabral HJ., Jick SS. Antihypertensive drugs and the risk of congenital anomalies. Pharmacotherapy. 2013; 33:476-482. DOI: 10.1002/phar.1212

39. Fabjan-Vodusek V., Kumer K., Osredkar J. et al. Correlation between uterine artery Doppler and the sFlt-1/PlGF ratio in different phenotypes of placental dysfunction. Hypertens Pregnancy. 2019;38(1):32-40. DOI: 10.1080/10641955.2018.1550579

40. Краснопольский В.И., Стрижаков А.Н., Радзинский В.Е. и соавт. Какой классификации гестозов (преэклампсии) должен придерживаться врач в повседневной работе? Журнал акушерства и женских болезней. 2013; 62(1): 5-9.

41. Неонатология: национальное руководство. Антонов А.Г., Арестова Н.Н., Байбарина Е.Н. и соавт. Под ред. Н.Н. Володина. М.: ГЭОТАР-Медиа, 2009. 848 с.

42. Yan L., Jin Y., Hang H., Yan B. The association between urinary tract infection during pregnancy and preeclampsia. A meta-analysis. Medicine. 2018; 97:36(e12192). DOI: 10.1097/MD.0000000000012192