Kidney disease and hypertension in pregnancy

1. What changes take place in the kidney during pregnancy?

The kidney undergoes anatomic and physiologic changes during normal pregnancy. The length of the kidney increases by 1 to 1.5 cm and there is hormonally mediated dilatation of the collecting system to a volume of about 300 cc. The resulting physiologic hydronephrosis makes it difficult to diagnose obstruction by ultrasound. The glomerular filtration rate increases by 50% during the first trimester so that the serum creatinine is expected to be 0.5 to 0.7 mg/dL. Pregnancy is also characterized by a reset osmotstat where the serum sodium is normally in the range of 134 mEq/L, but a water load can be excreted normally. Additionally, pregnancy is characterized by respiratory alkalosis with a compensatory drop in bicarbonate, making the normal bicarbonate in pregnancy 18 to 20 mEq/L.

2. How often do urinary tract infections occur during pregnancy?

Urinary stasis from the dilated collecting system predisposes to urinary tract infections. Asymptomatic bacteriuria occurs in 5% of pregnancies. Untreated, 30% of asymptomatic bacteriuria leads to pyelonephritis, which in pregnant women is frequently complicated by decreased kidney function/acute kidney injury, sepsis, and even acute respiratory distress syndrome (ARDS). Only 2% of healthy women with a negative urine culture on the first screening will develop a urinary tract infection (UTI) later in pregnancy, but women with preexisting kidney disease should be screened monthly.

3. What is the importance of preeclampsia?

Preeclampsia is the most common and important of the hypertensive disorders of pregnancy, affecting between 5% and 7% of pregnancies. Preeclampsia is a multisystem disease. The American College of Obstetrics and Gynecology does not require proteinuria if other end-organ disease is present. Severe preeclampsia is denoted by its most common symptoms, microangiopathic Hemolytic anemia, Elevated Liver enzymes and Low Platelets (HELLP syndrome). It can be accompanied by severe manifestations including acute kidney injury, stroke, blindness from vasoconstriction in the occipital lobe or retinal detachment, disseminated intravascular coagulation, hepatic rupture, or pulmonary edema. Preeclampsia may progress to seizures, a progression that changes the designation to eclampsia. The hypertension in preeclampsia is identified relative to prepregnancy blood pressure. A rise in systolic blood pressure of 30 mm Hg or a rise in diastolic blood pressure of 15 mm Hg raises the possibility of preeclampsia. The definitive treatment of preeclampsia is delivery of the baby and placenta, but depending on the severity of the preeclampsia, efforts may be made to postpone delivery if it occurs in the second trimester or early in the third trimester. Anticonvulsants, most commonly magnesium in the U.S., and antihypertensive drugs are usually required while getting the mother ready for delivery.

Over the last decade, long-term follow-up of large populations of women with preeclampsia has shown a subsequent increased risk of cardiovascular disease, kidney biopsy, and end-stage kidney disease (ESKD).

4. What is the pathophysiology of preeclampsia?

The initiating factor in preeclampsia is incomplete remodeling of uterine spiral arteries, which results in placental ischemia. The ischemic placenta produces high levels of the antiangiogenic factors, soluble Fms-like tyrosine kinase (sFlt1) and soluble endoglin which are released into the circulation. Levels of placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) are low. sFlt1 antagonizes the angiogenic activity of VEGF and PlGF, causing diffuse vasoconstriction and glomerular endothelial damage. Therapies targeting antiangiogenic factors to treat preeclampsia are an ongoing area of investigation. A different pathogenesis has been proposed for late-onset preeclampsia (more than 34 weeks gestation). In late preeclampsia, the problem may be maternal endothelial dysfunction in response to oxidative stress in the placenta.

5. What are the other hypertensive disorders of pregnancy?

The three other hypertensive disorders of pregnancy are chronic hypertension, chronic hypertension with superimposed preeclampsia, and gestational hypertension. Women with preexisting hypertension may become pregnant so that essential hypertension is seen during pregnancy. The diagnosis of essential hypertension is made by a blood pressure ≤140/90 before 20 weeks gestation with no other explanation or a diagnosis of essential hypertension before pregnancy. These women are at increased risk for preeclampsia, giving rise to essential hypertension with superimposed preeclampsia in 25%. Gestational hypertension is hypertension that occurs late in pregnancy and is not accompanied by proteinuria or other end-organ disease of preeclampsia. It resolves postpartum but is a predictor of future essential hypertension.