Pregnant Women With CKD Face Serious Health Risks
Chronic kidney disease (CKD) in pregnancy is associated with severe maternal morbidity and mortality even in the United States, according to new study findings. Women with CKD, including those who have received a kidney transplant, warrant early and close surveillance and multidisciplinary management before, during, and after pregnancy.
Kidney Failure, Cardiovascular Events, and Early Death
Robert M. Rossi, MD, of the University of Cincinnati College of Medicine in Ohio, and colleagues studied 38,374,326 women from the US National Inpatient Sample who delivered in a hospital setting during 2010-2020, 1 including 95,272 women (0.2%) with CKD. Severe maternal morbidity was more frequent in women with kidney disease than without (12.2% vs 0.7%). The risk for severe maternal morbidity was 6.4-fold higher in the presence of kidney disease, the investigators reported in the American Journal of Obstetrics & Gynecology MFM. The likelihood of acute renal failure was a significant 22-fold higher with CKD. The risks for acute myocardial infarction, cardiac arrest, and heart failure were more than 2-fold higher with CKD.
Kidney diseases significantly increased the risk of the mother dying by 4.1-fold, Dr Rossi’s team reported. In subgroup analyses, maternal death was significantly associated with diabetic nephropathy, obstructive or unspecified renal disease, and renovascular CKD by 7.3-, 12.9-, and 14.1-fold, respectively. To prevent 1 severe maternal morbidity event or maternal death, 2.6 and 45.0 patients with stage 3-5 CKD would need to receive a kidney transplant, respectively, Dr Rossi and colleagues estimated.
In addition, the risks for sepsis, temporary tracheostomy, shock, acute respiratory distress syndrome, and pulmonary edema/acute heart failure were 9.0-, 7.7-, 5.7-, 4.0-, and 3.6-fold higher with CKD, respectively.
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Women at any CKD stage may face complex pregnancy-related decisions and increased risks that are not adequately addressed by current guidelines.
Preeclampsia and Eclampsia
Women with CKD also had a 3.4-fold higher risk for hysterectomy and a 1.5-fold increased risk for eclampsia. CKD and kidney transplantation also correlated with preeclampsia, Cesarean delivery, preterm birth, stillbirth, and fetal growth restriction. In JAMA Network Open2, a separate team of investigators noted that severe maternal morbidity risks increase even in women without pre-pregnancy kidney, heart, or liver disease who develop preeclampsia, whether or not they also have chronic or gestational hypertension.
In a comparison of pregnant women with CKD published in Nephrology Dialysis Transplantation,7 women who developed early or late preeclampsia had higher risks of significant eGFR decline and end-stage kidney disease.
Another JAMA Network Open study3 including 13,828 mostly healthy pregnant women examined aspirin dose to prevent preeclampsia. No difference was found in the rates of preeclampsia or bleeding complications between women receiving the lower (75 mg) vs higher aspirin dose (150 to 160 mg) during pregnancy. Aspirin, especially higher doses, should be used cautiously in patients with CKD.
Preconception Planning and Early Nephrology Referral
Morbidity risks apply across CKD stages and etiologies, including in pregnant women with a history of kidney transplantation who have similar risks to patients with stage 1 CKD, Dr Rossi’s team emphasized. Black, Hispanic, and Native American women with CKD had a higher rate of severe maternal morbidity compared with White women, likely due in part to poor access to nephrology care.
“Preconception optimization of renal function and associated underlying co-morbidities, and equitable access to multidisciplinary specialty care during pregnancy are warranted for patients with CKD,” Dr Rossi’s team wrote.
Writing in BMC Nephrology,4 Nityasree Srialluri, MD, and Sumeska Thavarajah, MD, of Johns Hopkins School of Medicine in Baltimore, Maryland, called for early nephrology referral before stage 3 CKD and multidisciplinary care for reproductive age women with CKD.
“Current Kidney Disease Improving Global Outcomes (KDIGO) guidelines suggest nephrology referral primarily for advanced CKD stages or significant proteinuria. However, women at any CKD stage may face complex pregnancy-related decisions and increased risks that are not adequately addressed by these guidelines, warranting early specialty care,” they wrote.
According to data from the US National Health and Nutritional Examination Survey (NHANES),5 CKD awareness is lower in women aged 20-49 than in men. Other research has documented suboptimal CKD care among women.
Dr Srialluri and Dr Thavarajah emphasized the importance of family planning at early stages of CKD. Patients with CKD have lower fertility and are at risk for adverse pregnancy-associated outcomes, including CKD progression, a flare of their underlying kidney disease, and adverse pregnancy complications including pre-eclampsia, preterm
delivery, and small for gestational age infant.
Dr Srialluri and Dr Thavarajah noted that guideline-recommended sodium-glucose cotransporter-2 inhibitors, renin-angiotensin-aldosterone system inhibitors, mineralocorticoid receptor antagonists (MRAs), and glucagon-like peptide-1 (GLP1) agonists have teratogenic effects and are contraindicated during pregnancy, yet guidelines do not specify the timing of discontinuation of these drugs or reinitiation after pregnancy. A study published in JAMA Pediatrics6 urged caution when prescribing NSAIDs during pregnancy, particularly indomethacin and ketorolac in the first trimester, mefenamic acid and diclofenac in the second trimester, and ibuprofen in the third trimester, to ensure the safety of the babies’ kidneys.
Reproductive age women clearly need a multidisciplinary team.
“Nephrologists can focus on CKD progression and medication adjustments, obstetricians on pregnancy-specific risks, and primary care providers on broader contraceptive and health education, creating a supportive network for optimal patient outcomes,” Dr Srialluri and Dr Thavarajah wrote. They added that the ratio of soluble Fms-like tyrosine kinase 1 (s-Flt-1) over placental growth factor (PIGF) can help distinguish preeclampsia from CKD progression. Guidelines for reproductive health in CKD are warranted.
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