Prior Acute Kidney Injury May Contribute to Adverse Pregnancy Outcomes

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Acute kidney injury (AKI) is most often considered a concern for elderly and critically ill populations, but a new study indicates that it may also pose risks for pregnant women and their babies, even when women have recovered their kidney function before pregnancy. The findings, which are published in the Journal of the American Society of Nephrology, point to a newly defined group of high-risk women.

Previous research has shown that AKI can increase the risk of later developing chronic kidney disease (CKD) and dying prematurely, but the consequence of an episode of AKI on health outcomes relevant to young women—especially those who may become pregnant—has not been addressed fully. Several studies have reported adverse pregnancy outcomes in women with early stages of CKD, and even subclinical kidney dysfunction may jeopardize healthy pregnancies. Therefore, recovered AKI (r-AKI) may represent an under-recognized threat to women who wish to bear children.

To study whether a history of r-AKI increases a woman’s risk of later problems during pregnancy, Jessica Sheehan Tangren, MD, a Research Fellow in the Division of Nephrology at Massachusetts General Hospital, and her colleagues retrospectively studied all women who delivered infants between 1998 and 2007 at her institution: 105 women with r-AKI and 24,640 women without a history of kidney disease.

Women with r-AKI had an increased rate of preeclampsia compared with controls (23% vs. 4%). Also, infants of women with r-AKI were born earlier than infants of controls (average 37.6 vs. 39.2 weeks), with increased rates of small-for-gestational-age births (15% vs. 8%) and newborns admitted to the neonatal intensive care unit (26% vs. 8%). There were 189 perinatal deaths in the cohort, with significantly more deaths in the offspring of mothers with recovered AKI (3.0% vs. 0.8%); however, this association became non-significant in a multivariate logistic regression analysis.

Recovered AKI was linked with a 5.9-times increased risk of preeclampsia and a 2.4-times increased risk of adverse fetal outcomes, after adjustments were made for various patient factors including maternal age, body mass index, race, parity, history of diabetes, and diastolic blood pressure at first prenatal visit. When women with r-AKI and controls were matched 1:2 by age, race, body mass index, diastolic blood pressure, parity, and diabetes status, r-AKI was associated with a 4.7-times increased risk of preeclampsia and a 2.1-times increased risk of adverse fetal outcomes. A similar association between r-AKI and adverse pregnancy outcomes was observed in analyses excluding all women with diabetes, obesity, and hypertension.

“We believe that this study highlights an important finding that will be useful for medical providers caring for reproductive-age women,” Tangren said. In particular, health care providers should consider the study’s findings when counseling women with previous AKI—not just those with advanced preexisting kidney disease—about the risk of adverse outcomes in pregnancy.

The investigators stressed that the interaction between diseased kidneys and the feto-placental unit during gestation remains unknown and requires additional research. They hypothesize that in women with prior AKI, subclinical vascular endothelial injury may sensitize the vasculature to the toxic effects of circulating antiangiogenic factors that rise prior to term in all pregnancies. Additional animal and human studies are needed to test this potential explanation, however. “Our goal in future studies is to address why women with a history of AKI are at higher risk for pregnancy complications and to identify strategies to lower their risk,” Tangren said. They also would like to know if AKI severity is associated with future preeclampsia risk. In this study, because there were a small number of events in each AKI stage, the investigators did not have the power to address this relationship.

The varying rates of preeclampsia reported worldwide may be explained, at least partially, by the study’s findings, Tangren noted. Preeclampsia rates range from 1% to 15%, with higher rates reported in low-income countries. Also, rates of AKI are higher among young women in low-income countries.

Giorgina Piccoli MD, who was not involved with the study and is the Chair of the Division of Nephrology at the University of Torino in Italy, noted that the cross-talk between the kidney and the placenta is important. “[It is] no wonder perhaps if all types of kidney damage are reflected and amplified in pregnancy, a situation in which the kidney is under functional stress,” she said. “The study’s findings are in line with previous studies of our group and others that suggest an effect of even minor renal damage in the development of adverse pregnancy-related outcomes. I’m concerned about how many patients we do not follow as high- risk pregnancies, and about how much we have to do to offer the best treatment to all of our patients.”

The article, entitled “Pregnancy Outcomes Following Clinical Recovery from Acute Kidney Injury,” appeared online at http://jasn.asnjournals.org/ on December 22, 2016, doi: 10.1681/ASN.2016070806.