Pre-eclampsia and risk of later kidney disease: nationwide cohort study
BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l1516 (Published 29 April 2019) Cite this as: BMJ 2019;365:l1516
- Jonas H Kristensen, medical resident1,
- Saima Basit, statistician1,
- Jan Wohlfahrt, chief statistician1,
- Mette Brimnes Damholt, consultant nephrologist2,
- Heather A Boyd, senior researcher1
- 1Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark
- 2Department of Nephrology, Copenhagen University Hospital (Rigshospitalet), Blemdamsvej 9, DK-2100 Copenhagen Ø, Denmark
- Correspondence to: H Boyd hoy{at}ssi.dk
- Accepted 19 March 2019
ABSTRACT
Objective To investigate associations between pre-eclampsia and later risk of kidney disease.
Design Nationwide register based cohort study.
Setting Denmark.
Population All women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015.
Main outcome measure Hazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression.
Results The cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest.
Conclusion s Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.
Footnotes
Contributors: JHK conceived and designed the study; defined exclusion criteria and exposure, outcome, and covariate categories; interpreted the study findings; and drafted the manuscript. SB conceived and designed the study, acquired and analysed the data, interpreted the study findings, and critically reviewed the manuscript. JW designed the study, advised on selection and implementation of analytical methods, interpreted the study findings, and critically reviewed the manuscript. MBD conceived and designed the study, interpreted the study findings, and critically reviewed the manuscript. HAB conceived and designed the study, supervised and directed the conduct of the study, interpreted the study findings, and critically revised the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. JK, SB, JW, and HAB had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. HAB is the guarantor.
Funding: This work was partially supported by the Danish Council for Independent Research (DFF-4092-00213). The Danish Council for Independent Research had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The researchers acted independently from the study sponsor in all aspects of this study.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: SB was supported by a grant from the Danish Council for Independent Research; no other support for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Studies based solely on data from the Danish national registers do not need approval from the Danish research bioethics committees, as study participants are never contacted, and consent is not required for the use of register information. The study’s use of register data was covered by the approval extended by the Danish Data Protection Agency to all register based studies conducted by Statens Serum Institut (approval No 2015-57-0102).
Data sharing: This study is based on Danish national register data. These data do not belong to the authors but to the Danish Ministry of Health, and the authors are not permitted to share them, except in aggregate (as, for example, in a publication). However, interested parties can obtain the data on which the study was based by submitting a research protocol to the Danish Data Protection Agency (Datatilsynet) and then, once Data Protection Agency permission has been received, applying to the Ministry of Health’s Research Service (Forskerservice) at forskerservice@ssi.dk.
Transparency: The manuscript’s guarantor (HAB) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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