Abstract

Background Hypertensive disorders of pregnancy (HDP) (preeclampsia, gestational hypertension) are increasingly common complications of pregnancy. HDP are associated with increased risk of cardiovascular disease and end-stage kidney disease in women. Chronic kidney disease (CKD) is highly prevalent, but evidence for associations between HDP and CKD is 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 identify whether HDP are associated with CKD and whether this risk differs by CKD aetiology. Methods Using data from the Swedish Medical Birth Register, singleton live births from 1973–2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Preeclampsia was the main exposure of interest and 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, tubulo-interstitial, other/non-specific CKD. Cox proportional hazard regression models were used, adjusting for year of delivery, maternal age, country of origin, education level, antenatal BMI, smoking during pregnancy, gestational diabetes, and parity. Women with pre-pregnancy comorbidities were excluded. Results The final sample consisted of 1,924,409 women who had 3,726,554 singleton live-births. The mean age of women at first delivery was 27.0 (±5.1) years. Median follow-up was 20.7 (interquartile range 9.9–30.0) years. 90,917 women (4.7%) were diagnosed with preeclampsia, 43,964 (2.3%) had gestational hypertension, and 18,477 (0.9%) developed CKD. Women who had preeclampsia had a higher risk of developing CKD during follow-up (adjusted hazard ratio (aHR) 1.92, 95% CI 1.83–2.03). The risk differed by CKD subtype, and was higher for hypertensive CKD (aHR 3.72, 95% CI 3.05–4.53), diabetic CKD (aHR 3.94, 95% CI 3.38–4.60) and glomerular/proteinuric CKD (aHR 2.06, 95% CI 1.88–2.26). 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). Conclusion Women with history of HDP are at increased risk of CKD, particularly hypertensive or diabetic CKD. Preterm preeclampsia, recurrent preeclampsia, and preeclampsia complicated by pre-pregnancy obesity are all associated with higher risk of maternal CKD. Since 10% of women develop clinically significant CKD in their lifetime, the absolute risk of CKD related to HDP may be substantial. Women who experience HDP may benefit from future systematic renal monitoring to prevent CKD onset or progression.

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