By Martina McGrath, MD
September 26, 2017
Women with advanced chronic kidney disease (CKD) have long been known to be at increased risk of complications in pregnancy including preeclampsia, pre-term birth, small-for-dates offspring, and progression of underlying CKD following pregnancy.1 However, several recent studies have highlighted a less obvious connection between earlier stages of renal disease and adverse pregnancy outcomes.2,3
Tangren et al recently published an elegant analysis of a large database of pregnant women who delivered at Massachusetts General Hospital between 1998 and 2007.4 The analysis included singleton pregnancies, lasting past 20-weeks gestation. Patients with a history of acute kidney injury (AKI) were identified using a linked hospital database by assessing lab data as well as inpatient and outpatient notes and billing codes extending back for 10 years prior to the pregnancy. AKI was defined as an increase in serum creatinine to 1.5 times baseline value, occurring within seven days. Patients with CKD, (i.e., estimated GFR less than 90mls/min/1.73m2), proteinuria, known structural kidney disease (such as polycystic kidney disease) and conditions known to affect the kidneys (e.g., SLE) were excluded from the analysis.
105 women were identified who had a prior history of AKI with documented recovery to normal renal function prior to pregnancy (r-AKI group). The control population comprised 24,640 pregnancies in women without CKD or history of AKI. Around one-third of women in the control cohort had a serum creatinine available within six months of pregnancy. There was no difference between creatinine in these patients and those in the r-AKI group, indicating the baseline function was similar in both.
The results are striking, and indicate a marked increase in risk of pre-eclampsia in patients with prior AKI. Twenty-three perent of women with r-AKI had pre-eclampsia as compared to 4% of women in the control group, an almost six-fold increase in risk (OR 5.9, 95% CI 3.6-9.7). There were also significantly increased risks of other negative pregnancy outcomes, with greater than 1.5-fold increased risk of gestational hypertension, cesarean section, and shorter gestational age, with delivery occurring at 37.6 weeks in r-AKI patients versus 39.2 weeks in controls.
In terms of fetal outcomes, women with r-AKI were more likely to have small-for-dates gestation (15% as compared to 8% in controls), with higher rates of NICU admission and preterm delivery at <37 weeks in this group. A composite fetal outcome of perinatal death, NICU admission, small-for-dates and preterm delivery was over 2.5-fold more common in babies of mothers with r-AKI as compared to controls.
The authors have carried out very detailed analyses, including sensitivity and subgroup analyses such as: limiting the analysis to control patients where pre-pregnancy creatinine was available within six months of conception; matching for age, race, BMI, and diabetes status; limiting to nulliparous women (as prior AKI could relate to prior pre-eclampsia in some); and exclusion of those with diabetes, obesity and hypertension. In all of these scenarios, the findings of the analysis were unchanged and remained significant, indicating the history of AKI was the most significant factor differentiating the two groups of women and associated with increased risk.
Despite the very careful analytic approach taken by the authors, it is difficult to estimate how these findings apply to the broader population. The number of patients involved is small (only 105 women with r-AKI). Details were not available for the severity of AKI suffered by these young women prior to pregnancy. Also, this is a single-center study, in a major academic medical center; possibly treating patients with greater medical complexity than the majority of pregnant women. The retrospective nature of this analysis may fail to fully capture/control for this effect.
Despite these potential limitations, given the degree of increased risk, the findings are significant and certainly warrant further investigation. A history of prior AKI may be an important risk factor for negative pregnancy outcomes and if replicated in a larger, broader-based cohort, these findings could identify a cohort of at-risk mothers and babies who would benefit from closer monitoring, or possibly interventions such as aspirin5 to reduce their risk of pre-eclampsia and negative pregnancy outcomes.
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- Jones DC, Hayslett JP. Outcome of pregnancy in women with moderate or severe renal insufficiency. The New England journal of medicine 1996;335:226-32.
- Piccoli GB, Cabiddu G, Attini R, et al. Risk of Adverse Pregnancy Outcomes in Women with CKD. Journal of the American Society of Nephrology : JASN 2015;26:2011-22.
- Piccoli GB, Attini R, Vasario E, et al. Pregnancy and chronic kidney disease: a challenge in all CKD stages. Clinical journal of the American Society of Nephrology : CJASN 2010;5:844-55.
- Tangren JS, Powe CE, Ankers E, et al. Pregnancy Outcomes after Clinical Recovery from AKI. Journal of the American Society of Nephrology : JASN 2017;28:1566-74.
- Rolnik DL, Wright D, Poon LC, et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. The New England journal of medicine 2017;377:613-22.
Dr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.