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

Background 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. Conclusions 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. Author summaryWhy was this study done? Preeclampsia is associated with increased long-term risk of heart disease and end-stage kidney disease (ESKD; requiring dialysis or transplant) in women. Less is known about the long-term risk of chronic kidney disease (CKD) following preeclampsia, although it is much more common than ESKD. There are many different types of CKD, and we sought to identify whether preeclampsia was equally associated with different subtypes of CKD. Large-scale, high-quality datasets with long periods of follow-up are required to investigate this. What did the researchers do and find? We used nationally representative data from 1.9 million women (3.7 million live births) in Sweden to measure the risk of CKD following preeclampsia over a 41-year period. We controlled our analysis for multiple confounding factors, including maternal age, country of origin, education level, BMI, smoking, and gestational diabetes. We excluded women with underlying medical conditions who were at higher risk of CKD at baseline. Women who had preeclampsia had almost double the risk of developing any CKD during follow-up compared to women with no preeclampsia. They also had more than 3 times higher risk of CKD linked to high blood pressure (hypertensive CKD) or diabetes specifically. Women who experienced preterm preeclampsia, recurrent preeclampsia, or preeclampsia on a background of pre-pregnancy obesity were at highest risk of CKD. What do these findings mean? Our findings suggest that women with a history of preeclampsia are at increased risk of long-term CKD, particularly hypertensive or diabetic forms of CKD. Women who experience preeclampsia may benefit from future systematic renal monitoring.