Preeclampsia and risk of end stage kidney disease: a Swedish nationwide cohort study

Khashan, Ali S.; Evans, Marie; Kublickas, Marius; McCarthy, Fergus P.; Kenny, Louise C.; Stenvinkel, Peter; Fitzgerald, Tony; Kublickiene, Karolina

Preeclampsia and risk of end stage kidney disease: a Swedish nationwide cohort study

dc.contributor.author	Khashan, Ali S.
dc.contributor.author	Evans, Marie
dc.contributor.author	Kublickas, Marius
dc.contributor.author	McCarthy, Fergus P.
dc.contributor.author	Kenny, Louise C.
dc.contributor.author	Stenvinkel, Peter
dc.contributor.author	Fitzgerald, Tony
dc.contributor.author	Kublickiene, Karolina
dc.contributor.funder	Svenska Forskningsrådet Formas	en
dc.contributor.funder	Stockholms Läns Landsting	en
dc.contributor.funder	Swedish Kidney Foundation	en
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2019-09-23T10:03:50Z
dc.date.available	2019-09-23T10:03:50Z
dc.date.issued	2019-07-30
dc.description.abstract	Background: Preeclampsia has been suggested to increase the risk of end-stage kidney disease (ESKD); however, most studies were unable to adjust for potential confounders including pre-existing comorbidities such as renal disease and cardiovascular disease (CVD). We aimed to examine the association between preeclampsia and the risk of ESKD in healthy women, while taking into account pre-existing comorbidity and potential confounders. Methods and findings: Using data from the Swedish Medical Birth Register (MBR), women who had singleton live births in Sweden between 1982 and 2012, including those who had preeclampsia, were identified. Women with a diagnosis of chronic kidney disease (CKD), CVD, hypertension, or diabetes prior to the first pregnancy were excluded. The outcome was a diagnosis of ESKD, identified from the Swedish Renal Registry (SRR) from January 1, 1991, onwards along with the specified cause of renal disease. We conducted Cox proportional hazards regression analysis to examine the association between preeclampsia and ESKD adjusting for several potential confounders: maternal age, body mass index (BMI), education, native country, and smoking. This analysis accounts for differential follow-up among women because women had different lengths of follow-up time. We performed subgroup analyses according to preterm preeclampsia, small for gestational age (SGA), and women who had 2 pregnancies with preeclampsia in both. The cohort consisted of 1,366,441 healthy women who had 2,665,320 singleton live births in Sweden between 1982 and 2012. At the first pregnancy, women’s mean (SD) age and BMI were 27.8 (5.13) and 23.4 (4.03), respectively, 15.2% were smokers, and 80.7% were native Swedish. The overall median (interquartile range [IQR]) follow-up was 7.4 years (3.2–17.4) and 16.4 years (10.3–22.0) among women with ESKD diagnosis. During the study period, 67,273 (4.9%) women having 74,648 (2.8% of all pregnancies) singleton live births had preeclampsia, and 410 women developed ESKD with an incidence rate of 1.85 per 100,000 person-years. There was an association between preeclampsia and ESKD in the unadjusted analysis (hazard ratio [HR] = 4.99, 95% confidence interval [CI] 3.93–6.33; p < 0.001), which remained in the extensively adjusted (HR = 4.96, 95% CI 3.89–6.32, p < 0.001) models. Women who had preterm preeclampsia (adjusted HR = 9.19; 95% CI 5.16–15.61, p < 0.001) and women who had preeclampsia in 2 pregnancies (adjusted HR = 7.13, 95% CI 3.12–16.31, p < 0.001) had the highest risk of ESKD compared with women with no preeclampsia. Considering this was an observational cohort study, and although we accounted for several potential confounders, residual confounding cannot be ruled out. Conclusions: The present findings suggest that women with preeclampsia and no major comorbidities before their first pregnancy are at a 5-fold increased risk of ESKD compared with parous women with no preeclampsia; however, the absolute risk of ESKD among women with preeclampsia remains small. Preeclampsia should be considered as an important risk factor for subsequent ESKD. Whether screening and/or preventive strategies will reduce the risk of ESKD in women with adverse pregnancy outcomes is worthy of further investigation.	en
dc.description.sponsorship	Swedish Research Council (grant No 2009-1068)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.articleid	e1002875	en
dc.identifier.citation	Khashan, A. S., Evans, M., Kublickas, M., McCarthy, F. P., Kenny, L. C., Stenvinkel, P., Fitzgerald, T. and Kublickiene, K. (2019) 'Preeclampsia and risk of end stage kidney disease: A Swedish nationwide cohort study', PLOS Medicine, 16(7),. e1002875. (18pp.) DOI: 10.1371/journal.pmed.1002875	en
dc.identifier.doi	10.1371/journal.pmed.1002875	en
dc.identifier.eissn	1549-1676
dc.identifier.endpage	18	en
dc.identifier.issn	1549-1277
dc.identifier.issued	7	en
dc.identifier.journaltitle	PLOS Medicine	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/8594
dc.identifier.volume	16	en
dc.language.iso	en	en
dc.publisher	PLOS	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2272/IE/Irish Centre for Fetal and Neonatal Translational Research (INFANT)/	en
dc.relation.uri	https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002875
dc.rights	©2019 Khashan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.subject	Preeclampsia	en
dc.subject	End stage	en
dc.subject	Kidney disease	en
dc.subject	Swedish	en
dc.title	Preeclampsia and risk of end stage kidney disease: a Swedish nationwide cohort study	en
dc.type	Article (peer-reviewed)	en