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Observational Study
. 2019 Jul 30;16(7):e1002875.
doi: 10.1371/journal.pmed.1002875. eCollection 2019 Jul.

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

Ali S Khashan  1   2 , Marie Evans  3 , Marius Kublickas  4 , Fergus P McCarthy  2   5 , Louise C Kenny  6 , Peter Stenvinkel  3 , Tony Fitzgerald  1   7 , Karolina Kublickiene  3
Affiliations
Observational Study

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

Ali S Khashan et al. PLoS Med. .

Erratum in

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.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: ME has participated in an advisory board meeting (Astellas) and has received payment for lectures by Astellas in the field of renal anemia. LCK is a minority shareholder in Metabolomic Diagnostics, a company which has licenced IP pertaining to the early pregnancy prediction of biomarkers to predict pre-eclampsia. LCK has also given talks about pre-eclampsia at symposia sponsored by Roche and Alere.

Figures

Fig 1
Fig 1. Flow chart of the study population.
CKD, chronic kidney disease; CVD, cardiovascular disease.
Fig 2
Fig 2. Cumulative risk of ESKD in relation to preeclampsia.
The cumulative hazard plot was based on a cohort of 1,358,543 women with 2,654,641 births. Black: women with no preeclampsia; blue: women with at least one preeclampsia diagnosis; 95% CIs in dashed lines. CI, confidence interval; ESKD, end-stage kidney disease.
Fig 3
Fig 3. Cumulative risk of ESKD in relation to preeclampsia in 1 or 2 pregnancies among women who had 2 prepregnancies during the study period.
The cumulative hazard plot was based on the cohort of 650,455 women who had 2 pregnancies recorded in the Swedish MBR during the study period; N = 1,291,179. Black: women with no preeclampsia; blue: women who had preeclampsia in 1 pregnancy; green: women who had preeclampsia in 2 pregnancies. 95% CIs in dashed lines. CI, confidence interval; ESKD, end-stage kidney disease; MBR, Medical Birth Register.
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Grants and funding

The study was partly funded by the Irish Centre for Fetal and Neonatal Translational Research (INFANT) (grant no. 12/RC/2272), Strategic Research Programme in Diabetes at Karolinska Institutet (Swedish Research Council grant No 2009-1068), the Stockholm County Council (ALF), and the Swedish Kidney Foundation. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.