Hypertensive disorders of pregnancy and the risk of chronic kidney disease: A Swedish registry-based cohort study

Autoři: Peter M. Barrett aff001;  Fergus P. McCarthy aff002;  Marie Evans aff004;  Marius Kublickas aff005;  Ivan J. Perry aff001;  Peter Stenvinkel aff004;  Ali S. Khashan aff001;  Karolina Kublickiene aff004
Působiště autorů: School of Public Health, University College Cork, Cork, Ireland aff001;  Irish Centre for Maternal and Child Health Research, University College Cork, Cork, Ireland aff002;  Department of Obstetrics & Gynaecology, Cork University Maternity Hospital, Cork, Ireland aff003;  Division of Renal Medicine, Department of Clinical Intervention, Science and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden aff004;  Department of Obstetrics & Gynaecology, Karolinska University Hospital, Stockholm, Sweden aff005
Vyšlo v časopise: Hypertensive disorders of pregnancy and the risk of chronic kidney disease: A Swedish registry-based cohort study. PLoS Med 17(8): e32767. doi:10.1371/journal.pmed.1003255
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1003255



Hypertensive disorders of pregnancy (HDP) (preeclampsia, gestational hypertension) are associated with an increased risk of end-stage kidney disease (ESKD). Evidence for associations between HDP and chronic kidney disease (CKD) is more limited and inconsistent. The underlying causes of CKD are wide-ranging, and HDP may have differential associations with various aetiologies of CKD. We aimed to measure associations between HDP and maternal CKD in women who have had at least one live birth and to identify whether the risk differs by CKD aetiology.

Methods and findings

Using data from the Swedish Medical Birth Register (MBR), singleton live births from 1973 to 2012 were identified and linked to data from the Swedish Renal Register (SRR) and National Patient Register (NPR; up to 2013). Preeclampsia was the main exposure of interest and was treated as a time-dependent variable. Gestational hypertension was also investigated as a secondary exposure. The primary outcome was maternal CKD, and this was classified into 5 subtypes: hypertensive, diabetic, glomerular/proteinuric, tubulointerstitial, and other/nonspecific CKD. Cox proportional hazard regression models were used, adjusting for maternal age, country of origin, education level, antenatal BMI, smoking during pregnancy, gestational diabetes, and parity. Women with pre-pregnancy comorbidities were excluded.

The final sample consisted of 1,924,409 women who had 3,726,554 singleton live births. The mean (±SD) age of women at first delivery was 27.0 (±5.1) years. Median follow-up was 20.7 (interquartile range [IQR] 9.9–30.0) years. A total of 90,917 women (4.7%) were diagnosed with preeclampsia, 43,964 (2.3%) had gestational hypertension, and 18,477 (0.9%) developed CKD. Preeclampsia was associated with a higher risk of developing CKD during follow-up (adjusted hazard ratio [aHR] 1.92, 95% CI 1.83–2.03, p < 0.001). This risk differed by CKD subtype and was higher for hypertensive CKD (aHR 3.72, 95% CI 3.05–4.53, p < 0.001), diabetic CKD (aHR 3.94, 95% CI 3.38–4.60, p < 0.001), and glomerular/proteinuric CKD (aHR 2.06, 95% CI 1.88–2.26, p < 0.001). More modest associations were observed between preeclampsia and tubulointerstitial CKD (aHR 1.44, 95% CI 1.24–1.68, p < 0.001) or other/nonspecific CKD (aHR 1.51, 95% CI 1.38–1.65, p < 0.001). The risk of CKD was increased after preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity. Women who had gestational hypertension also had increased risk of developing CKD (aHR 1.49, 95% CI 1.38–1.61, p < 0.001). This association was strongest for hypertensive CKD (aHR 3.13, 95% CI 2.47–3.97, p < 0.001). Limitations of the study are the possibility that cases of CKD were underdiagnosed in the national registers, and some women may have been too young to have developed symptomatic CKD despite the long follow-up time. Underreporting of postpartum hypertension is also possible.


In this study, we found that HDP are associated with increased risk of maternal CKD, particularly hypertensive or diabetic forms of CKD. The risk is higher after preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity. Women who experience HDP may benefit from future systematic renal monitoring.

Klíčová slova:

Cardiovascular disease risk – Gestational diabetes – Hypertensive disorders in pregnancy – Chronic kidney disease – Labor and delivery – Preeclampsia – Pregnancy – Preterm birth


1. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291–310. doi: 10.1016/j.preghy.2018.05.004 29803330

2. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstetrics and gynecology. 2013;122(5):1122–31. doi: 10.1097/01.AOG.0000437382.03963.88 24150027

3. Valdiviezo C, Garovic VD, Ouyang P. Preeclampsia and hypertensive disease in pregnancy: their contributions to cardiovascular risk. Clin Cardiol. 2012;35(3):160–5. doi: 10.1002/clc.21965 22389120

4. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. Journal of the American College of Cardiology. 2011;57(12):1404–23. doi: 10.1016/j.jacc.2011.02.005 21388771

5. Tooher J, Chiu CL, Yeung K, Lupton SJ, Thornton C, Makris A, et al. High blood pressure during pregnancy is associated with future cardiovascular disease: an observational cohort study. BMJ Open. 2013;3(7).

6. Covella B, Vinturache AE, Cabiddu G, Attini R, Gesualdo L, Versino E, et al. A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia. Kidney Int. 2019;96(3):711–27. doi: 10.1016/j.kint.2019.03.033 31352975

7. Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. The New England journal of medicine. 2008;359(8):800–9. doi: 10.1056/NEJMoa0706790 18716297

8. Khashan AS, Evans M, Kublickas M, McCarthy FP, Kenny LC, Stenvinkel P, et al. Preeclampsia and risk of end stage kidney disease: A Swedish nationwide cohort study. PLoS Med. 2019;16(7):e1002875. doi: 10.1371/journal.pmed.1002875 31361741

9. Dai L, Chen Y, Sun W, Liu SL. Association Between Hypertensive Disorders During Pregnancy and the Subsequent Risk of End-Stage Renal Disease: A Population-Based Follow-Up Study. Journal of Obstetrics and Gynaecology Canada. 2018;40(9):1129–38. doi: 10.1016/j.jogc.2018.01.022 29934233

10. Wang IK, Muo CH, Chang YC, Liang CC, Chang CT, Lin SY, et al. Association between hypertensive disorders during pregnancy and end-stage renal disease: A population-based study. CMAJ. 2013;185(3):207–13. doi: 10.1503/cmaj.120230 23339156

11. Rangaswami J, Naranjo M, McCullough PA. Preeclampsia as a form of type 5 cardiorenal syndrome: An underrecognized entity in women's cardiovascular health. CardioRenal Medicine. 2018;8(2):160–72. doi: 10.1159/000487646 29627841

12. Ruiz S, Pergola PE, Zager RA, Vaziri ND. Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney Int. 2013;83(6):1029–41. doi: 10.1038/ki.2012.439 23325084

13. Yu L, Wang T, Que R, Yang J, Wang Z, Jiang X, et al. The potentially protective role of ATP-binding cassette transporters in preeclampsia via Nrf2. Pregnancy Hypertens. 2019;18:21–8. doi: 10.1016/j.preghy.2019.08.002 31445436

14. Barrett PM, McCarthy FP, Kublickiene K, Cormican S, Judge C, Evans M, et al. Adverse Pregnancy Outcomes and Long-term Maternal Kidney Disease: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(2):e1920964.

15. Ayansina D, Black C, Hall SJ, Marks A, Millar C, Prescott GJ, et al. Long term effects of gestational hypertension and pre-eclampsia on kidney function: Record linkage study. Pregnancy Hypertension-an International Journal of Womens Cardiovascular Health. 2016;6(4):344–9.

16. Kristensen JH, Basit S, Wohlfahrt J, Damholt MB, Boyd HA. Pre-eclampsia and risk of later kidney disease: nationwide cohort study. Bmj. 2019;365:l1516. doi: 10.1136/bmj.l1516 31036557

17. Männistö T, Mendola P, Vääräsmäki M, Järvelin MR, Hartikainen AL, Pouta A, et al. Elevated blood pressure in pregnancy and subsequent chronic disease risk. Circulation. 2013;127(6):681–90. doi: 10.1161/CIRCULATIONAHA.112.128751 23401113

18. McDonald SD, Yusuf S, Walsh MW, Lonn E, Teo K, Anand SS, et al. Increased cardiovascular risk after pre-eclampsia in women with dysglycaemia. Diabetic medicine: a journal of the British Diabetic Association. 2013;30(1):e1–7.

19. Riise HKR, Sulo G, Tell GS, Igland J, Nygard O, Iversen AC, et al. Association Between Gestational Hypertension and Risk of Cardiovascular Disease Among 617 589 Norwegian Women. J Am Heart Assoc. 2018;7(10).

20. The Swedish Medical Birth Register—A summary of content and quality. Stockholm: Centre for Epidemiology. The National Board of Health and Welfare; 2003.

21. Barrett PM, McCarthy FP, Evans M, Kublickas M, Perry IJ, Stenvinkel P, et al. Stillbirth is associated with increased risk of long-term maternal renal disease: a nationwide cohort study. Am J Obstet Gynecol. 2020. Feb 26;S0002-9378(20)30219-2.

22. Ros HS, Cnattingius S, Lipworth L. Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study. Am J Epidemiol. 1998;147(11):1062–70. doi: 10.1093/oxfordjournals.aje.a009400 9620050

23. WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. Geneva: World Health Organization; 2011.

24. Marsal K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta paediatrica (Oslo, Norway: 1992). 1996;85(7):843–8.

25. National Kidney Foundation. How to classify CKD 2019. [cited 2020 July 29]. Available from: https://www.kidney.org/professionals/explore-your-knowledge/how-to-classify-ckd.

26. Austin PC, Lee DS, Fine JP. Introduction to the Analysis of Survival Data in the Presence of Competing Risks. Circulation. 2016;133(6):601–9. doi: 10.1161/CIRCULATIONAHA.115.017719 26858290

27. Lykke JA, Langhoff-Roos J, Sibai BM, Funai EF, Triche EW, Paidas MJ. Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension. 2009;53(6):944–51. doi: 10.1161/HYPERTENSIONAHA.109.130765 19433776

28. Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, et al. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. BMJ. 2003;326(7394):845. doi: 10.1136/bmj.326.7394.845 12702615

29. Feig DS, Shah BR, Lipscombe LL, Wu CF, Ray JG, Lowe J, et al. Preeclampsia as a risk factor for diabetes: a population-based cohort study. PLoS Med. 2013;10(4):e1001425. doi: 10.1371/journal.pmed.1001425 23610560

30. Stuart JJ, Tanz LJ, Missmer SA, Rimm EB, Spiegelman D, James-Todd TM, et al. Hypertensive Disorders of Pregnancy and Maternal Cardiovascular Disease Risk Factor Development: An Observational Cohort Study. Annals of internal medicine. 2018;169(4):224–32. doi: 10.7326/M17-2740 29971437

31. Garovic VD. The role of the podocyte in preeclampsia. Clin J Am Soc Nephrol. 2014;9(8):1337–40. doi: 10.2215/CJN.05940614 25035271

32. Ponticelli C, Moroni G. Is preeclampsia a risk for end-stage renal disease? Kidney Int. 2019;96(3):547–9. doi: 10.1016/j.kint.2019.05.009 31445581

33. McDonald SD, Han Z, Walsh MW, Gerstein HC, Devereaux PJ. Kidney disease after preeclampsia: a systematic review and meta-analysis. Am J Kidney Dis. 2010;55(6):1026–39. doi: 10.1053/j.ajkd.2009.12.036 20346562

34. Aykas F, Solak Y, Erden A, Bulut K, Dogan S, Sarli B, et al. Persistence of cardiovascular risk factors in women with previous preeclampsia: A long-term follow-up study. Journal of Investigative Medicine. 2015;63(4):641–5. doi: 10.1097/JIM.0000000000000189 25738648

35. Schmidlin CJ, Dodson MB, Zhang DD. Filtering through the role of NRF2 in kidney disease. Archives of Pharmacal Research. 2019.

36. Smith GC, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births. Lancet (London, England). 2001;357(9273):2002–6.

37. Lykke JA, Langhoff-Roos J, Lockwood CJ, Triche EW, Paidas MJ. Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery. Paediatr Perinat Epidemiol. 2010;24(4):323–30. doi: 10.1111/j.1365-3016.2010.01120.x 20618721

38. Riise HK, Sulo G, Tell GS, Igland J, Nygard O, Vollset SE, et al. Incident Coronary Heart Disease After Preeclampsia: Role of Reduced Fetal Growth, Preterm Delivery, and Parity. J Am Heart Assoc. 2017;6(3).

39. Burton GJ, Yung HW, Cindrova-Davies T, Charnock-Jones DS. Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia. Placenta. 2009;30 Suppl A:S43–8.

40. Almasi O, Pariente G, Kessous R, Sergienko R, Sheiner E. Association between delivery of small-for-gestational-age neonate and long-term maternal chronic kidney disease. Journal of Maternal-Fetal & Neonatal Medicine. 2016;29(17):2861–4.

41. Dai L, Chen Y, Sun W, Liu S. Association Between Hypertensive Disorders During Pregnancy and the Subsequent Risk of End-Stage Renal Disease: A Population-Based Follow-Up Study. Journal of Obstetrics and Gynaecology Canada. 2018.

42. Kessous R, Shoham-Vardi I, Pariente G, Sergienko R, Sheiner E. Long-term maternal atherosclerotic morbidity in women with pre-eclampsia. Heart. 2015;101(6):442–6. doi: 10.1136/heartjnl-2014-306571 25564558

43. Cho GJ, Kim HY, Park JH, Ahn KH, Hong SC, Kim HJ, et al. Prepregnancy Factors Are Associated with Development of Hypertension Later in Life in Women with Pre-Eclampsia. Journal of women's health (2002). 2019;28(7):984–9. doi: 10.1089/jwh.2018.7165 30284940

44. Alma LJ, De Groot CJM, De Menezes RX, Hermes W, Hordijk PL, Kovacevic I. Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: High BMI is key. European journal of obstetrics, gynecology, and reproductive biology. 2018;225:62–9. doi: 10.1016/j.ejogrb.2018.04.003 29677687

45. Covella B, Vinturache AE, Cabiddu G, Attini R, Gesualdo L, Versino E, et al. A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia. Kidney Int. 2019.

46. Paauw ND, Luijken K, Franx A, Verhaar MC, Lely AT. Long-term renal and cardiovascular risk after preeclampsia: towards screening and prevention. Clinical Science. 2016;130(4):239–46. doi: 10.1042/CS20150567 26769659

47. Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, et al. Global Prevalence of Chronic Kidney Disease—A Systematic Review and Meta-Analysis. PLoS ONE. 2016;11(7):e0158765. doi: 10.1371/journal.pone.0158765 27383068

48. Gasparini A, Evans M, Coresh J, Grams ME, Norin O, Qureshi AR, et al. Prevalence and recognition of chronic kidney disease in Stockholm healthcare. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association. 2016;31(12):2086–94.

49. Collaboration GBDCKD. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England). 2020.

50. Rapporteringen till nationella kvalitetsregister och hälsodataregistren. Jämförelser av täckningsgrader 2014. Stockholm: Socialstyrelsen; 2014.

51. Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450. doi: 10.1186/1471-2458-11-450 21658213

52. Surkan PJ, Hsieh CC, Johansson AL, Dickman PW, Cnattingius S. Reasons for increasing trends in large for gestational age births. Obstetrics and gynecology. 2004;104(4):720–6. doi: 10.1097/01.AOG.0000141442.59573.cd 15458892

53. Fadl HE, Simmons D. Trends in diabetes in pregnancy in Sweden 1998–2012. BMJ Open Diabetes Res Care. 2016;4(1):e000221. doi: 10.1136/bmjdrc-2016-000221 27547412

54. Leon LJ, McCarthy FP, Direk K, Gonzalez-Izquierdo A, Prieto-Merino D, Casas JP, et al. Preeclampsia and Cardiovascular Disease in a Large UK Pregnancy Cohort of Linked Electronic Health Records: A CALIBER Study. Circulation. 2019;140(13):1050–60. doi: 10.1161/CIRCULATIONAHA.118.038080 31545680

55. Schisterman EF, Cole SR, Platt RW. Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology. 2009;20(4):488–95. doi: 10.1097/EDE.0b013e3181a819a1 19525685

Článek vyšel v časopise

PLOS Medicine

2020 Číslo 8
Nejčtenější tento týden
Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

Hypertenze a hypercholesterolémie – synergický efekt léčby
nový kurz
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Úloha kombinovaných preparátů v léčbě arteriální hypertenze
Autoři: prof. MUDr. Martin Haluzík, DrSc.

Autoři: MUDr. Ladislav Korábek, CSc., MBA

Terapie roztroušené sklerózy v kostce
Autoři: MUDr. Dominika Šťastná, Ph.D.

Všechny kurzy
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se