Editorial
Preeclampsia and the Long-term Risk of Kidney Failure
Related Article, p. 498
C hronic kidney disease (CKD) affects approxi-
mately 1 in 10 adults worldwide.1 Although
progression to end-stage renal disease (ESRD) is
expected in only 3% of the CKD population, it is
associated with major health burdens.1 Knowledge of
the constellation of features that put a person at high
risk for ESRD can inuence decisions around
screening, prognostication, and even treatment. Many
of these risk factors are well recognized, including
older age, hypertension, diabetes, cardiovascular
disease, and family history of kidney disease.1 More
recent data show that women with a history of
preeclampsia have a higher risk for ESRD in later life
than women without such a history.2-6
Studies that attempt to describe this relationship
highlight associations between preeclampsia and
postpartum evidence of microalbuminuria,2,3 receipt
of a kidney biopsy,4 and ESRD.5,6 These ndings
are in keeping with large cohort studies showing that
preeclampsia in a rst pregnancy is associated with
elevated risk for future ischemic heart disease, hy-
pertension, stroke, and death from cardiovascular
causes.3,7 However, these reports have been limited
by the uncertain validity of diagnostic codes used to
identify preeclampsia and incomplete assessment of
comorbid conditions prior to pregnancy. In this issue
of AJKD, Kattah et al8 revisit the association
between preeclampsia and ESRD and highlight the
importance of considering the role of shared risk
factors in this assessment.
Kattah et al used registry data from Olmsted
County, MN, to identify all women who had a preg-
nancy resulting in childbirth during a 35-year period.
Using linked data from the US Renal Data System,
they identied 44 women who developed ESRD after
pregnancy and 88 women without ESRD, matched on
year of birth, age at pregnancy, and parity among the
cohort of 34,581 women. The authors reviewed each
of these medical records to identify pregnancies
complicated by preeclampsia using a diagnostic al-
gorithm consistent with that used in clinical practice
and validated against blinded review by maternal-fetal
medicine experts. Using a conditional logistic
regression model, they found that the odds of having
ESRD were 4 times greater in women with a history
of preeclampsia during pregnancy compared with
those without. This association was signicant after
adjusting for race, education, preexisting hyperten-
sion, and diabetes. However, this association was
attenuated after adjusting for obesity. The authors
Am J Kidney Dis. 2017;69(4):487-488
conclude that this extends our understanding of the
association by identifying a subset of women with
a history of preeclampsia who develop ESRD and
highlight obesity as a confounder not recognized in
previous studies.
Several mechanisms have been proposed to
account for the association between preeclampsia
and later development of kidney disease. One possi-
bility is that preeclampsia causes direct kidney injury
resulting in proteinuria or hypertension that continues
to mediate subsequent injury.9,10 In support of this
theory, studies have found that 20% to 40% of women
with preeclampsia have microalbuminuria 3 to 5 years
after pregnancy, compared to just 2% of women
without preeclampsia.2,11 However, because preg-
nancy is typically the rst health care encounter for
young women, many women have not had kidney
function tests prior to pregnancy (.50% in the Kattah
et al study) and prepregnancy kidney disease may be
underappreciated. In this setting, preeclampsia may
simply be exacerbating preexisting disease that is
recognized only when proteinuria or hypertension
fails to subside postpartum. This appears to be
the case in up to 20% of women who develop
preeclampsia prior to 30 weeks gestation.12 Alter-
natively, preeclampsia and kidney disease may be
caused by factors that mediate both pathophysiologic
processes, such as obesity, hypertension, insulin
resistance, or endothelial dysfunction.13-15 Anti-
angiogenic factors have been proposed to be key
elements in the pathogenesis of preeclampsia and in
the progression of CKD.16,17
Kattah et al overcome a major limitation of
previous studies by using diagnostic algorithms to
ascertain comorbid conditions from medical records
rather than administrative database codes that tend
to lack sensitivity. They demonstrate a strong asso-
ciation between preeclampsia and ESRD that is
independent of several shared risk factors when
assessed individually. However, these data do not
further our understanding of what is mediating the
risk for ESRD after preeclampsia or how a history of
preeclampsia should alter management with respect to
screening or treatment. Further research is necessary
to better understand the mechanisms underlying these
Address correspondence to Ainslie M. Hildebrand, MD,
Division of Nephrology, University of Alberta, 11-107 Clinical
Sciences Building, 152 University Campus, Edmonton, Alberta,
Canada T6G 2G3. E-mail: amhildeb@ualberta.ca
2017 by the National Kidney Foundation, Inc.
0272-6386
http://dx.doi.org/10.1053/j.ajkd.2017.01.002
487
 Hildebrand, Hladunewich, and Garg

associations and move beyond an assessment of the 6. Vikse BE, Irgens LM, Leivestad T, Skjaerven R,
association to guiding how such information should Iversen BM. Preeclampsia and the risk of end-stage renal disease.
N Engl J Med. 2008;359:800-809.
be used in practice.
7. Bellamy L, Casas J-P, Hingorani AD, Williams DJ. Pre-
eclampsia and risk of cardiovascular disease and cancer in later life:
Ainslie M. Hildebrand, MD systematic review and meta-analysis. BMJ. 2007;335(7627):974.
University of Alberta 8. Kattah A, Scantlebury D, Agarwal S, et al. Preeclampsia
Edmonton, Alberta, Canada and ESRD: the role of shared risk factors. Am J Kidney Dis.
2017;69(4):498-505.
Michelle A. Hladunewich, MD, MSc 9. Arnlv J, Evans JC, Meigs JB, et al. Low-grade albuminuria
University of Toronto and incidence of cardiovascular disease events in nonhypertensive
and nondiabetic individuals: the Framingham Heart Study.
Toronto, Ontario, Canada Circulation. 2005;112:969-975.
10. Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K,
Amit X. Garg, MD, PhD Orth SR. Combining GFR and albuminuria to classify CKD
Western University improves prediction of ESRD. J Am Soc Nephrol. 2009;20:1069-
London, Ontario, Canada 1077.
11. Nisell H, Lintu H, Lunell NO, Mllerstrm G, Pettersson E.
ACKNOWLEDGEMENTS Blood pressure and renal function seven years after pregnancy
complicated by hypertension. Br J Obstet Gynaecol. 1995;102:
Support: None. 876-881.
Financial Disclosure: The authors declare that they have no
12. Murakami S, Saitoh M, Kubo T, Koyama T, Kobayashi M.
relevant nancial interests.
Renal disease in women with severe preeclampsia or gestational
Peer Review: Evaluted by a Co-Editor and Editor-in-Chief
proteinuria. Obstet Gynecol. 2000;96:945-949.
Levey.
13. Joffe GM, Esterlitz JR, Levine RJ, et al. The relationship
between abnormal glucose tolerance and hypertensive disorders of
REFERENCES pregnancy in healthy nulliparous women. Am J Obstet Gynecol.
1. Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney 1998;179:1032-1037.
disease: global dimension and perspectives. Lancet. 2013;382: 14. Cotter AM, Molloy AM, Scott JM, Daly SF. Elevated
260-272. plasma homocysteine in early pregnancy: a risk factor for the
2. Bar J, Kaplan B, Wittenberg C, et al. Microalbuminuria after development of severe preeclampsia. Am J Obstet Gynecol.
pregnancy complicated by pre-eclampsia. Nephrol Dial Trans- 2001;185:781-785.
plant. 1999;14:1129-1132. 15. Sibai BM, Gordon T, Thom E, et al. Risk factors for
3. McDonald SD, Han Z, Walsh MW, Gerstein HC, preeclampsia in healthy nulliparous women: a prospective multi-
Devereaux PJ. Kidney disease after preeclampsia: a systematic center study. Am J Obstet Gynecol. 1995;172:642-648.
review and meta-analysis. Am J Kidney Dis. 2010;55:1026-1039. 16. Levine RJ, Maynard SE, Qian C, et al. Circulating angio-
4. Vikse BE, Irgens LM, Bostad L, Iversen BM. Adverse genic factors and the risk of preeclampsia. N Engl J Med.
perinatal outcome and later kidney biopsy in the mother. J Am Soc 2004;350:672-683.
Nephrol. 2006;17:837-845. 17. Kang DH, Anderson S, Kim YG, et al. Impaired angio-
5. Wang I-K, Muo C-H, Chang Y-C, et al. Association between genesis in the aging kidney: vascular endothelial growth factor and
hypertensive disorders during pregnancy and end-stage renal thrombospondin-1 in renal disease. Am J Kidney Dis. 2001;37:
disease: a population-based study. CMAJ. 2013;85:207-213. 601-611.

488 Am J Kidney Dis. 2017;69(4):487-488