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Pregnancy in women with nondialysis chronic kidney disease

Pregnancy in women with nondialysis chronic kidney disease
Authors:
Michelle A Hladunewich, MD, FRCPC, MSc
John Vella, MD, FACP, FRCP, FASN, FAST
Phyllis August, MD, MPH
Section Editors:
Jeffrey S Berns, MD
Lynn L Simpson, MD
Deputy Editors:
Albert Q Lam, MD
Kristen Eckler, MD, FACOG
Literature review current through: Dec 2022. | This topic last updated: Aug 03, 2022.

INTRODUCTION — Women with significant chronic kidney disease (CKD), particularly those with advanced CKD, are much less likely to become pregnant or have an uncomplicated pregnancy compared with women with normal kidney function. Even mild CKD is associated with a higher risk of adverse maternal and fetal outcomes, including worsening of maternal kidney function, proteinuria, and hypertension, as well as preterm birth and fetal growth restriction.

This topic reviews the effects of pregnancy on maternal kidney function and the effects of kidney function on pregnancy outcomes and provides recommendations for counseling and management of pregnancy in women with CKD. Related topics on the management of pregnancy in women on dialysis and pregnancy in women with other causes of CKD and kidney transplant are presented separately:

(See "Pregnancy in women on dialysis".)

(See "Pregnancy in women with systemic lupus erythematosus".)

(See "Kidney transplantation in adults: Sexual and reproductive health after kidney transplantation".)

EPIDEMIOLOGY — Little is known about the frequency of pregnancy among women with nondialysis CKD as there are no population-based studies [1]. The available data are extrapolated from the transplant population. In an observational study including 16,195 female kidney transplant recipients aged 15 to 45 years (63 percent with estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), the pregnancy rate during the first three posttransplant years was 33 per 1000 female transplant recipients between 1990 and 2003; 55 percent ended in a live birth [2]. The pregnancy rate among transplant recipients in this study was much lower than that reported among the general United States population during the same time period, as reported by the United States National Vital Statistics System (greater than 100 per 1000 in each year between 1990 and 2000) [3]. It is unclear if this is a true deficit in fertility or a reflection of counseling practices given the frequent use of potentially teratogenic medications in this patient population. (See "Kidney transplantation in adults: Sexual and reproductive health after kidney transplantation".)

PREGNANCY OUTCOMES — CKD increases the risk of adverse maternal and fetal outcomes (table 1) [4-8]. In a meta-analysis of 23 observational studies that included over 506,000 pregnancies, CKD was associated with higher risk of preeclampsia (odds ratio [OR] 10.4, 95% CI 6.3-17.1), premature delivery (OR 5.7, 95% CI 3.3-10), small for gestational age/low birth weight (OR 4.9, 95% CI 3-7.8), cesarean section (OR 2.7, 95% CI 2-3.4), and pregnancy failure (OR 1.8, 95% CI 1-3.1) [5].

Effect of low GFR – Even mild reductions in glomerular filtration rate (GFR) may increase the risk of preeclampsia, gestational hypertension, and possibly premature delivery, as has been demonstrated among kidney donors [9-11]. (See "Kidney transplantation in adults: Risk of living kidney donation", section on 'Maternal and fetal outcomes'.)

The risk increases as GFR declines and in the setting of proteinuria and hypertension. In a study that included 504 pregnancies among women with CKD, the risk for preterm delivery, small for gestational age, or need for neonatal intensive care unit was 34 percent for patients with stage 1 CKD (defined as kidney damage and estimated GFR [eGFR] >90 mL/min/1.73 m2) versus 90 percent for those stage 4 or 5 (defined as eGFR <30 mL/min/1.73 m2) [12]. In women with stage 1 CKD, preterm delivery was associated with hypertension (OR 3.4, 95% CI 1.9-6.2) and proteinuria (OR 3.7, 95% CI 1.6-8.4). (See "Definition and staging of chronic kidney disease in adults", section on 'Staging of CKD'.)

Effect of proteinuria – Higher levels of proteinuria appear to adversely affect pregnancy outcomes. In the meta-analysis cited above [5], a subgroup analysis found that the odds of preeclampsia and premature delivery were higher in women who had albuminuria ≥300 mg/24 hours (or total proteinuria ≥500 mg/24 hours) compared with those who had albuminuria 30 to 300 mg/24 hours (or total proteinuria 150 to 500 mg/24 hours).

Effect of hypertension – Pre-existing maternal hypertension is associated with increased risk of preterm birth, particularly before 34 weeks gestation [13]. In addition, fetal survival is lower when hypertension is uncontrolled (ie, >140/90 mmHg) preconception [14-16]. The relative risk of fetal death has been estimated to be approximately 10-fold higher in women with a mean arterial pressure >105 mmHg at conception compared with those with spontaneous or therapeutically achieved normotension [16].

EFFECTS OF PREGNANCY ON KIDNEY DISEASE — Pregnancy can hasten the progression of CKD. The risk is dependent upon the baseline glomerular filtration rate (GFR), proteinuria, and hypertension [17].

If patients have only mildly decreased GFR (ie, estimated GFR [eGFR] >60 mL/min/1.73 m2), the risk of progression is low [5,7,18-21]. In a meta-analysis of eight cohort studies with 1268 CKD patients with well-preserved kidney function, there was no increase in renal outcomes (including doubling of the serum creatinine, 50 percent decline in eGFR or creatinine clearance, or end-stage kidney disease [ESKD]) compared with women with CKD who were not pregnant [5].

By contrast, women with low baseline GFR are at much higher risk for worsening of CKD during pregnancy [4,14,17,22,23]. This was demonstrated in a study of 57 women (70 pregnancies) who had a serum creatinine >1.4 mg/dL (124 micromol/L) [4]. Forty-three percent had a pregnancy-related loss of kidney function, and 10 percent progressed to ESKD by 12 months postpartum; among eight patients, seven had a decline in kidney function during pregnancy, and only one had stable kidney function before and immediately after pregnancy. The risk of acceleration was highest (33 versus 2 percent) among those with an initial plasma creatinine concentration above 2.0 mg/dL (177 micromol/L) [4]. In a much later study that stratified patients according to GFR stage, the risk of deterioration of kidney function was 7.6, 12.6, 16.2, and 20 percent for CKD patients with eGFR >90, 60 to 89, 30 to 59, and 15 to 29 mL/min/1.73 m2, respectively [7].

During pregnancy, proteinuria and hypertension also increase the risk of progression of CKD [22,24]. The effect of proteinuria was best demonstrated by a prospective study that assessed 49 women with an eGFR <60 mL/min/1.73 m2 stratified by the degree of proteinuria [24]. Women with an eGFR <40 mL/min/1.73 m2 and >1 gram of proteinuria, but not those with either reduced eGFR or proteinuria alone, showed significantly hastened kidney function decline postpartum (0.55±0.39 increased to 1.17±1.23 mL/min/month prior to and after pregnancy, respectively). The risk of progression of CKD may exceed 50 percent in patients who also have uncontrolled hypertension [22].

Proteinuria increases in approximately one-half of cases, and hypertension develops or worsens in approximately one-quarter of cases [25-30]. Severe hypertension can occur, potentially leading to deterioration in kidney function and even maternal cardiovascular complications, premature delivery, or poor fetal outcome [14]. Marked worsening of edema also can be seen in women with the nephrotic syndrome. These changes generally improve after delivery, but a subset of women have accelerated disease progression to ESKD in the postpartum period.

Although the etiology of kidney disease may be a determinant of worsening kidney disease, we believe there are insufficient data to make this conclusion [15,22,27,31,32].

PRECONCEPTION CARE

Contraception — As pregnancy in women with CKD is associated with increased maternal and fetal risks, contraceptive counseling is an active part of preconception care. We advise contraceptive use until pregnancy is actively pursued. There are many variables that impact contraceptive choice, including method efficacy, duration of action, presence of hormones, need for daily maintenance, and timing of return of fertility (table 2). Women with CKD have additional concerns, including the impact of the contraceptive on their disease, the presence of other medical disorders such as hypertension, and anticipated time course of their illness, all of which must be balanced against the very significant risks associated with an unintended pregnancy among CKD patients. Both the World Health Organization and the United States' Centers for Disease Control and Prevention provide tables of medical eligibility criteria for contraceptive use in women with various characteristics and medical disorders. (See "Contraception: Counseling and selection".)

While the patient ultimately selects her contraceptive method, we take the following approach to thinking about contraception in women with CKD:

For women who desire the most effective contraception or durable contraception, we discuss long-acting reversible contraceptives (LARCs), including the copper intrauterine device (IUD), levonorgestrel-releasing IUDs, and the etonogestrel implant (figure 1). These methods have failure rates of less than 1 percent, do not require daily or monthly patient action, and last from 3 to 10 years, depending on the device. LARC methods are similar in efficacy to sterilization but have no surgical risk. However, for women who do not desire future fertility, surgical sterilization (male or female) is a reasonable option.

LARC methods can be used in most women with CKD, regardless of disease severity. For women at increased risk of arterial or venous thromboembolic events, IUDs do not increase the risk. However, as the risk of thromboembolic events in users of the etonogestrel implant is controversial, we avoid the etonogestrel implant in women at increased risk of thromboembolism who are candidates for, and amenable to, other options. Despite early theoretical concerns, there is no evidence that IUDs increase the risk of infection among women who have CKD or are on immunosuppression [33,34].

Contraceptive selection and the attributes of various contraceptive methods are presented separately:

(See "Contraception: Counseling and selection".)

(See "Intrauterine contraception: Background and device types".)

(See "Intrauterine contraception: Candidates and device selection".)

(See "Etonogestrel contraceptive implant".)

(See "Overview of female permanent contraception".)

(See "Vasectomy".)

For women who desire pregnancy in a shorter time frame or women who do not find LARC methods acceptable, we discuss depot medroxyprogesterone acetate (DMPA) injections, progestin-only oral pills, and combined estrogen-progestin products (oral pills, transdermal patch, and vaginal rings). Although not as effective as LARC, these methods are highly effective when used correctly and consistently but require regular action on the part of the user (figure 1). However, additional concerns exist for use of these methods in women with CKD, particularly women with osteopenia, hypertension, and/or increased risk of thromboembolic disease.

Depot medroxyprogesterone acetate (DMPA) – DMPA is a highly effective contraceptive that has the advantage of every-13-weeks dosing. However, we generally avoid DMPA in women who are currently or have recently been treated with glucocorticoids and calcineurin inhibitors, as these treatments are associated with an increased risk of low bone density or osteopenia, which are contraindications to DMPA use [35,36]. (See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits" and "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

Progestin-only pills (POPs) – POPs can be taken by women with CKD, including those with increased risk for thromboembolism or who have hypertension. However, these agents may be inconvenient for some women, as they must be taken at the same time of the day for full effect and are less effective than combined estrogen-progestin contraceptives. (See "Progestin-only pills (POPs) for contraception".)

Combined estrogen-progestin contraceptives – Combined estrogen-progestin contraceptives include oral pills, a transdermal patch, and vaginal rings. Specific to women with CKD, these methods are not preferred if other modalities are available and acceptable to the patient. One major concern is that estrogen-containing contraceptives increase the risk of both cardiovascular and venous thromboembolic events, to which CKD patients are already vulnerable. In addition, combined hormonal contraception is generally avoided in women with hypertension, even if the disease is adequately controlled by medication [37,38]. (See "Combined estrogen-progestin contraception: Side effects and health concerns".)

For combined hormonal pills, there is a theoretical risk that oral contraceptive agents may hasten the progression of CKD by activating the renin-angiotensin system (RAS) and by increasing the risk for hypertension [37,39-42]. Increased RAS activity is suggested by increased renal vascular resistance and filtration fraction and a more robust response to RAS inhibition among users of oral contraceptives [37,40-42]. Combined oral contraceptive agents have also been associated with increased risk for the development of microalbuminuria, even after adjustment for age, hypertension, diabetes, obesity, hyperlipidemia, and smoking (adjusted odds ratios [OR] 1.90, 95% CI 1.23-2.93) [43]. A small, prospective study of diabetic patients reported an almost ninefold increased risk of conversion from microalbuminuria to macroalbuminuria among individuals using the oral contraceptive pill (adjusted OR 8.90, 95% CI 1.79-44.36) [40].

The transdermal patch does not activate the RAS to the same degree, and there are no data to suggest that it hastens progression of CKD [44]. However, we do not use transdermal contraceptives in patients with nephrotic syndrome, as transdermal contraceptives may increase the risk of venous thromboembolism and thrombotic stroke [45]. Data on the use of the vaginal contraceptive rings in women with CKD are lacking; indications are extrapolated from data on combined hormonal pills. (See "Contraception: Transdermal contraceptive patches" and "Contraception: Hormonal contraceptive vaginal rings".)

For women who desire only a coital-dependent method of contraception, we discuss use of diaphragm with spermicide or the contraceptive sponge. The typical-use first-year pregnancy rates are approximately 17 percent for both methods [46]. However, for contraceptive sponge users, contraceptive efficacy varies based on parity, with typical-use first-year pregnancy rates of 14 percent for nulliparous women and 27 percent for parous women. Other coital-dependent contraceptives, including the cervical cap and spermicide alone, have unintended pregnancy rates of 20 to 30 percent and are therefore not advised for women who desire to avoid pregnancy. (See "Pericoital (on demand) contraception: Diaphragm, cervical cap, spermicides, and sponge".)

Of note, we advise consistent condom use (male or female) for all women at risk of acquiring a sexually transmitted infection.

Preconception counseling — We ask all reproductive-age women about their desires for pregnancy at every visit. Patients are educated that pregnancy in the setting of CKD is considered high risk and benefits from a multidisciplinary effort involving both a high-risk obstetrician and nephrologist. We discuss the following issues with the patient prior to conception:

Contraceptive methods to avoid unintended pregnancy. (See 'Contraception' above.)

Pregnancy outcomes (both maternal and fetal) in the setting of CKD. (See 'Pregnancy outcomes' above.)

Maternal risks, including both potential obstetric complications and risks to the kidneys. (See 'Maternal complications' below and 'Effects of pregnancy on kidney disease' above.)

Management of medications before, during, and after pregnancy. (See 'Management of medications' below.)

Timing of conception – Ideally, pregnancy in women with CKD should be planned in order to ensure better maternal and fetal outcomes. In general, conception is more likely to occur and pregnancies have better outcomes early in the course of CKD than in advanced CKD. Comorbidities such as systemic lupus erythematosus (SLE) and diabetes should be optimally controlled prior to conception.

(See "Pregnancy in women with systemic lupus erythematosus", section on 'Preconception evaluation'.)

(See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

A discussion of preconception care for the general population is presented in detail separately. (See "The preconception office visit".)

Baseline evaluation — In all nondialysis CKD patients who are considering becoming pregnant, we advise a multidisciplinary evaluation that includes a nephrologist and a maternal-fetal medicine specialist (high-risk obstetrician). We perform the following baseline evaluation prior to conception:

Assessment of the patient's medication history for potential teratogenic or fetotoxic medications (discontinue and/or substitute medications that have been identified to be potentially teratogenic or fetotoxic [eg, angiotensin-converting enzyme (ACE) inhibitors]) (See 'Management of medications' below.)

Vaccinations – Patients should receive standard vaccinations included in obstetric care. (See "Immunizations during pregnancy".)

Blood pressure. (See 'Hypertension' below.)

Serum creatinine, bicarbonate, and electrolytes.

Liver function tests.

Complete blood count. (See 'Anemia' below.)

Urinalysis and spot urine protein-to-creatinine ratio from a first or second morning void (and, if proteinuria is present, a 24-hour urine collection for protein) [47,48].

Fasting plasma glucose and glycated hemoglobin (A1C) in patients with pregestational diabetes mellitus. (See "Pregestational (preexisting) diabetes mellitus: Obstetric issues and management", section on 'First trimester'.)

Assessment of disease activity in patients with SLE. (See "Pregnancy in women with systemic lupus erythematosus", section on 'Risk assessment' and "Pregnancy in women with systemic lupus erythematosus", section on 'Specific laboratory testing'.)

In patients with undiagnosed CKD, some clinicians obtain a renal ultrasound to rule out structural, congenital, or cystic kidney diseases in the patient.

Management of medications

ACE inhibitors and ARBs — Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are often prescribed to nonpregnant patients with CKD for their antihypertensive and antiproteinuric effects, these medications should not be used during pregnancy, since they are associated with fetal abnormalities. Their use prior to pregnancy in women in childbearing years is controversial, and the risks and benefits must be individualized to each patient. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)

In general, as soon as a patient expresses desire for pregnancy, we stop the ACE inhibitors or ARBs and transition her to other medication for blood pressure control. However, for CKD patients who have significant proteinuria and no immunological treatment options (eg, diabetic kidney disease or kidney scarring), we continue ACE inhibitors or ARBs up until the detection of conception (at which time the medications are stopped). The rationale is that, among such patients, conception may take months or even years, during which time the ACE inhibitor or ARB may provide renal protection. The teratogenicity of ACE inhibitors and ARBs during the first trimester has not been conclusively shown; however there is sufficient concern to emphasize the importance of discontinuing these drugs if pregnancy is suspected and until it is confirmed. We advise women with regular menstrual periods to discontinue ACE inhibitors or ARBs and be tested for pregnancy if their period is delayed by more than two days. A negative pregnancy test should be repeated in a few days if menses have not resumed. Women with irregular menses can be regularly screened with pregnancy tests. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy", section on 'First-trimester exposure'.)

After delivery, ACE inhibitors may be resumed. Captopril, enalapril, and quinapril are not excreted into breast milk [49,50]. Human data on the secretion of candesartan and olmesartan are limited; decisions to resume these medications must balance the maternal benefits against potential risks to the neonate [51,52]. (See 'Postpartum care' below.)

Diuretics — Diuretics can be used in pregnant women with CKD if they have volume-mediated hypertension or signs of volume overload. We recommend consideration of dose reduction, if appropriate, to avoid possible volume contraction and electrolyte abnormalities [53,54]. Loop diuretics such as furosemide have been used safely in pregnant women. Women treated with diuretics in pregnancy should be monitored for electrolyte disturbances (eg, hypokalemia, hyponatremia).

Immunosuppressive agents — Women with CKD who are in childbearing years may be treated with immunosuppressive medications. The safety of specific immunosuppressive medications during pregnancy is discussed elsewhere. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)

The use of immunosuppressive medications during pregnancy for specific diseases is also discussed in related topic reviews.

Monitoring for pregnancy — Women with reproductive potential and not using contraception, particularly those on ACE inhibitors or ARBs, should be followed closely for pregnancy. Women who have regular periods are tested with serum beta-human chorionic gonadotropin (hCG) as soon as they miss a period or if menses is delayed for more than two days. All positive serum beta-hCG tests are followed up with an ultrasound to confirm diagnosis. Women with irregular menses can be regularly screened with pregnancy tests. (See 'Diagnosis of pregnancy' below.)

Diagnosis of pregnancy — In all women with CKD, we diagnose pregnancy using both a serum beta-hCG and an ultrasound. Among women suspected of being pregnant because of an elevated serum beta-hCG, the ultrasound confirms the presence of a viable fetus and estimates the gestational age. (See "Clinical manifestations and diagnosis of early pregnancy".)

Particularly among individuals with severe CKD (defined as estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2), pregnancy cannot be diagnosed using the serum beta-hCG alone. As serum beta-hCG is renally excreted, serum levels may be increased in the absence of pregnancy in women with advanced CKD or end-stage kidney disease (ESKD) [25].

MANAGEMENT DURING PREGNANCY

Maternal and fetal monitoring — Pregnant women with CKD should be monitored jointly by a nephrologist and by a maternal-fetal medicine specialist. General principles of management are discussed below.

Maternal – For obstetric care, we see patients at least monthly during the early first trimester, every two weeks by the second trimester, and weekly by the third trimester. Some patients require even closer follow-up throughout pregnancy.

The following assessments should be performed at least once per trimester and more often as clinically indicated:

Blood pressure (in addition to daily monitoring at home) (see 'Hypertension' below and 'Maternal complications' below)

Serum creatinine, bicarbonate, and electrolytes (see 'Management of CKD during pregnancy' below)

Fasting blood glucose in patients with diabetes mellitus

Complete blood count and differential (see 'Anemia' below)

Liver function tests

Urinalysis (and a urine culture if the dipstick reveals white blood cells or nitrates) and spot urine protein-to-creatinine ratio or urine albumin-to-creatinine ratio (see 'Maternal complications' below)

Whole blood trough tacrolimus (or cyclosporine) levels (in patients taking these medications)

In addition, in patients without a history of pregestational diabetes, we perform oral glucose tolerance testing to screen for gestational diabetes at 24 to 28 weeks of gestation or sooner in patients with risk factors, such as those receiving glucocorticoids and/or calcineurin inhibitors. (See "Gestational diabetes mellitus: Screening, diagnosis, and prevention", section on 'Screening for GDM'.)

Fetal – Obstetrical follow-up in this high-risk population typically includes a first-trimester screen in conjunction with an ultrasound assessment of nuchal translucency or a maternal serum screen in the second trimester to assess for chromosomal abnormalities including Down syndrome. As a serum human chorionic gonadotropin (hCG) is one component of both the first-trimester combined test and the second-trimester quadruple test, false-positive tests can occur in women with advanced CKD. As such, assessment of cell-free fetal DNA or more invasive testing including chorionic villous sampling or an amniocentesis may be necessary.

(See "Down syndrome: Overview of prenatal screening".)

(See "First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18".)

(See "Prenatal screening for common aneuploidies using cell-free DNA".)

A detailed ultrasound to assess fetal anatomy is typically performed between 18 to 20 weeks. We do a placental scan to assess placental morphology and Doppler flow at approximately 22 weeks. After 26 weeks, fetal growth is assessed as often as biweekly with weekly biophysical profiles if indicated.

(See "Overview of antepartum fetal assessment".)

(See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)

(See "Short cervix before 24 weeks: Screening and management in singleton pregnancies".)

Nutrition — Attention to nutritional considerations and proper weight gain are essential for a successful pregnancy [55]. Evaluation and follow-up by a dietician familiar with the requirements of pregnancy and CKD may be helpful.

Our approach for nondialysis CKD patients is the same as for pregnant women without CKD. We generally do not limit dietary phosphate, although we provide dietary counseling to limit nonnutritive sources of phosphate if the patient develops mild hyperphosphatemia. (See "Nutrition in pregnancy: Dietary requirements and supplements".)

Prevention of preeclampsia — Patients with CKD are considered to be at high risk for preeclampsia. Low-dose aspirin therapy has been shown to decrease the risk of preeclampsia in women at moderate to high risk of the disease, but studies have not included patients with CKD. However, the safety of low-dose aspirin in the general high-risk obstetric population has been well documented. In pregnant patients with CKD, we weigh the potential risks and benefits of low-dose aspirin therapy and offer treatment to those without any contraindications to aspirin use. The role of aspirin in the prevention of preeclampsia is discussed in more detail elsewhere. (See "Preeclampsia: Prevention", section on 'Low-dose aspirin'.)

Delivery

Mode of delivery — Vaginal delivery is the preferred mode of delivery if there are no obstetric contraindications. In most women, elective delivery is indicated if labor has not occurred by the estimated date of confinement. Even for low-risk women, there is little benefit in allowing the pregnancy to extend beyond this date, and maternal and/or perinatal risk may increase [56,57]. We suggest scheduling delivery by 39 to 40 weeks of gestation if the patient or fetus does not have an indication for earlier delivery [58]. Cesarean delivery is performed for standard obstetric indications.

Preterm intervention — Preterm delivery may be necessary in the presence of severe preeclampsia, fetal growth restriction, or nonreassuring fetal testing (eg, fetal distress). The indications for delivery in the setting of severe preeclampsia, fetal growth restriction, or fetal distress are usually the same as for the general population.

(See "Preeclampsia with severe features: Expectant management remote from term", section on 'Delivery'.)

(See "Preeclampsia: Antepartum management and timing of delivery", section on 'Timing of delivery'.)

(See "Fetal growth restriction: Pregnancy management and outcome", section on 'Delivery'.)

Among CKD patients, an additional consideration is what is the appropriate intervention if kidney function significantly and progressively declines. Generally, options include termination (if early in pregnancy) or delivery (if late in pregnancy). In some circumstances, the patient may elect to continue the pregnancy despite the continued deterioration of kidney function, occasionally requiring dialysis. Indications to initiate dialysis are discussed below. (See 'Indications to initiate hemodialysis' below.)

Use of magnesium sulfate — Many women get magnesium sulfate before delivery, either to prevent seizures in preeclampsia or to reduce the risk of cerebral palsy before preterm birth of an infant <32 weeks. Women with reduced glomerular filtration rate (GFR) will have an exaggerated rise in serum magnesium and may develop magnesium toxicity at the usual doses of administration; therefore extreme caution is advised when treating women with reduced GFR (<30 mL/min). The approach to dosing of magnesium varies among clinicians. (See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Dosing in renal insufficiency'.)

In all cases, serum magnesium levels should be followed and the patient monitored clinically for evidence of toxicity. (See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Signs of magnesium toxicity'.)

Management of CKD during pregnancy

Hypertension — Pregnant women with CKD have a high prevalence of chronic hypertension and are frequently treated with antihypertensive medications. Specific blood pressure targets for pregnant CKD patients have not been defined [59]. We generally try to maintain blood pressure between 120/70 and 149/90 mmHg. In a 2015 trial (Control of Hypertension in Pregnancy Study [CHIPS]) that randomly assigned pregnant women with gestational or chronic hypertension to diastolic blood pressure treatment targets of 85 or 100 mmHg, there were no differences in maternal, fetal, or neonatal outcomes for the two blood pressure targets, although fewer women in the lower diastolic blood pressure target group developed severe hypertension [60]. Medications with an acceptable safety profile in pregnancy include nifedipine (and most calcium channel blockers), labetalol, and methyldopa. Diuretics may be necessary in women with hypertension associated with edema and reduced GFR. (See "Treatment of hypertension in pregnant and postpartum patients".)

Metabolic bone disease — We are unaware of any guidelines that address management of CKD-mineral and bone disorder (CKD-MBD) during pregnancy. The alterations in calcium, phosphate, vitamin D, and parathyroid hormone (PTH) during pregnancy that have been observed in normal pregnancy [61,62] have not been assessed in pregnant women with CKD. Most women with near-normal GFR will not require any specific treatment for CKD-MBD during pregnancy. Those with more advanced CKD can be managed similarly to their management prior to conception, with the understanding that pregnancy-related hormonal changes, as well as renal hemodynamic adjustments, may alter levels of calcium, phosphorus, vitamin D, and PTH. Thus for women on treatment, we recommend that calcium, phosphorus, 25-hydroxyvitamin D, and PTH levels be monitored at least once each trimester. (See 'Maternal and fetal monitoring' above.)

If phosphate binders are required, then calcium carbonate is preferred as there are limited pregnancy data on other phosphate binders (ie, sevelamer, lanthanum carbonate, calcium acetate). Severe hyperphosphatemia is not common during pregnancy, even among patients with advanced CKD. Mild hyperphosphatemia is usually effectively treated with dietary counseling that limits the intake of nonnutritive sources of phosphate. Phosphate binders may reduce the absorption of fat-soluble vitamins and folic acid. (See 'Nutrition' above.)

Calcitriol may be used before and during pregnancy, and the indications are similar for the nonpregnant CKD patient. (See "Management of secondary hyperparathyroidism in adult nondialysis patients with chronic kidney disease", section on 'Treat persistent and progressive hyperparathyroidism'.)

We generally do not use cinacalcet during pregnancy, because there are limited data regarding safety.

Anemia — The indications for erythropoiesis-stimulating agent (ESA) use during pregnancy are similar as for nonpregnant CKD patients (see "Treatment of anemia in nondialysis chronic kidney disease", section on 'Indications and contraindications'). Pregnant women often require higher doses of ESAs to maintain an adequate red cell mass since the physiologic changes and demands of pregnancy may result in worsening of anemia. The target hemoglobin concentration is the same as for nonpregnant CKD patients. We suggest giving ESAs to nondialysis CKD patients who have a hemoglobin <10 g/dL, provided that the transferrin saturation (TSAT) is >25 percent and ferritin >200 ng/mL. We suggest targeting hemoglobin levels between 10 and 11.5 g/dL using the lowest possible ESA dose. ESAs do not cross the placenta because of their large molecular weight. (See "Treatment of anemia in nondialysis chronic kidney disease", section on 'Target hemoglobin value'.)

We give oral and intravenous (IV) iron preparations as necessary to maintain adequate iron stores. When providing IV iron, we use iron sucrose rather than other formulations, which are less well studied in pregnancy. Preparations other than iron sucrose may contain benzyl alcohol, which can pass into breast milk. (See "Anemia in pregnancy", section on 'Treatment of iron deficiency'.)

Indications to initiate hemodialysis — If the estimated GFR (eGFR) declines below 20 mL/min/1.73 m2 or the blood urea nitrogen (BUN) increases >50 to 60 mg/dL (18 to 21 mmol/L), we consider the elective initiation of dialysis. This is different from the approach for nonpregnant CKD patients in whom there is no minimum eGFR or threshold BUN that provides an absolute indication to begin dialysis in the absence of symptoms. However, this decision must be individualized.

The rationale for starting dialysis at a relatively high eGFR is that untreated CKD of this severity is associated with very poor pregnancy outcomes, including polyhydramnios, preterm delivery, and poor fetal growth. However, the benefits of aggressive dialysis have only been shown in studies of women with end-stage kidney disease (ESKD) who were already on dialysis at the start of pregnancy. (See "Pregnancy in women on dialysis" and "Pregnancy in women on dialysis", section on 'Dialysis prescription and administration'.)

The indications for initiation of dialysis (eg, signs and symptoms of uremia; persistent volume overload; refractory acidosis, hyperkalemia, or hyperphosphatemia) are the same for pregnant CKD patients as for the nonpregnant CKD population. (See "Indications for initiation of dialysis in chronic kidney disease".)

Maternal complications — Significant potential complications specific to pregnant women with CKD include preeclampsia, gestational diabetes mellitus (GDM), and infection.

The diagnosis of preeclampsia is challenging in this patient population because of preexisting proteinuria, reduced GFR, and hypertension. Close monitoring for the development of the nonrenal manifestations of preeclampsia include fetal and placental indicators of compromise including poor fetal growth, dropping platelet counts, and increasing liver function tests (table 3). In some centers, though not all, angiogenic markers may be used.

(See "Overview of antepartum fetal assessment".)

(See "Preeclampsia: Clinical features and diagnosis".)

Women with CKD who are being treated with immunosuppressive medications (such as glucocorticoids and/or calcineurin inhibitors) are at increased risk of GDM and should be screened earlier. Although there are little data in the general CKD population, one study reported a higher risk of GDM in pregnant kidney transplant recipients compared with the general United States population (8.0 percent versus 3.9 percent, respectively) [63]. (See 'Maternal and fetal monitoring' above and "Gestational diabetes mellitus: Screening, diagnosis, and prevention".)

In addition, women on immunosuppression are at increased risk for infection and should be carefully monitored. Bacterial urinary tract infections are common in normal pregnancy, and the development of pyelonephritis has been associated with adverse pregnancy outcomes.

(See 'Maternal and fetal monitoring' above.)

(See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)

(See "Kidney transplantation in adults: Sexual and reproductive health after kidney transplantation".)

POSTPARTUM CARE — Postpartum care is similar among women with and without CKD. There are no contraindications to breastfeeding among CKD patients. (See "Overview of the postpartum period: Normal physiology and routine maternal care".)

Among patients who have indications (ie, hypertension or significant proteinuria), we resume an angiotensin-converting enzyme (ACE) inhibitor, even if breastfeeding. We use either captopril, enalapril, or quinapril, all of which have been shown to be absent in breast milk [49,50]. We do not use angiotensin receptor blockers (ARBs), as they have not been adequately studied.

We continue erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron as necessary in all patients.

We monitor serum creatinine levels and spot urine protein-to-creatinine ratio (or albumin-to-creatinine ratio) to reestablish the patient's kidney function and degree of proteinuria postpartum, respectively. In patients who are taking calcineurin inhibitors, calcineurin inhibitor levels must be closely monitored for several weeks postpartum and doses should be appropriately adjusted to maintain the desired target levels.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topic (see "Patient education: Systemic lupus erythematosus and pregnancy (Beyond the Basics)").

SUMMARY AND RECOMMENDATIONS

Women with significant chronic kidney disease (CKD), particularly those with advanced CKD, are much less likely to become pregnant or have an uncomplicated pregnancy compared with women with normal kidney function. Even mild CKD is associated with a higher risk of adverse maternal and fetal outcomes, including worsening of maternal kidney function, proteinuria, and hypertension, as well as preterm birth and fetal growth restriction. (See 'Introduction' above.)

CKD increases the risk of adverse maternal and fetal outcomes (table 1) and has been associated with a higher risk of preeclampsia, premature delivery, small for gestational age/low birth weight, cesarean section, and pregnancy failure. Even mild reductions in glomerular filtration rate (GFR) may increase the risk of preeclampsia, gestational hypertension, and possibly premature delivery. The risk increases as GFR declines and in the settings of proteinuria and hypertension. Higher levels of proteinuria also adversely affect pregnancy outcomes. Fetal survival is lower when hypertension is uncontrolled (ie, >140/90 mmHg) preconception. (See 'Pregnancy outcomes' above.)

Pregnancy can hasten the progression of CKD. The risk is dependent upon the baseline GFR, proteinuria, and hypertension. (See 'Effects of pregnancy on kidney disease' above.)

As pregnancy in women with CKD is associated with increased maternal and fetal risks, contraceptive counseling is an active part of preconception care. We advise contraceptive use until pregnancy is actively pursued. Women with CKD have unique concerns, including the impact of the contraceptive on their disease, the presence of other medical disorders such as hypertension, and anticipated time course of their illness, all of which must be balanced against the very significant risks associated with an unintended pregnancy among CKD patients. (See 'Contraception' above.)

We ask all reproductive-age women about their desires for pregnancy at every visit. Patients are educated that pregnancy in the setting of CKD is considered high risk and benefits from a multidisciplinary effort involving both a high-risk obstetrician and nephrologist. (See 'Preconception counseling' above.)

In all nondialysis CKD patients who are considering becoming pregnant, we advise a multidisciplinary evaluation that includes a nephrologist and a maternal-fetal medicine specialist (high-risk obstetrician). Women with reproductive potential and not using contraception should be followed closely for pregnancy. (See 'Baseline evaluation' above and 'Monitoring for pregnancy' above.)

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should not be used during pregnancy, since they are associated with fetal abnormalities. In general, as soon as a patient expresses desire for pregnancy, we stop the ACE inhibitors or ARBs and transition her to other medication (eg, nifedipine, labetalol, methyldopa) for blood pressure control. However, for CKD patients who have significant proteinuria and no immunological treatment options (eg, diabetic kidney disease or kidney scarring), we continue ACE inhibitors or ARBs up until the detection of conception (at which time they are stopped). (See 'ACE inhibitors and ARBs' above.)

Diuretics can be used in pregnant women with CKD if they have volume-mediated hypertension or signs of volume overload. We suggest consideration of dose reduction, if appropriate, to avoid possible volume contraction. (See 'Diuretics' above.)

In all women with CKD, we diagnose pregnancy using both a serum beta-human chorionic gonadotropin (hCG) and an ultrasound. Among women suspected of being pregnant because of an elevated serum beta-hCG, the ultrasound confirms the presence of a viable fetus and estimates the gestational age. (See 'Diagnosis of pregnancy' above.)

For obstetric care, we see patients at least monthly during the early first trimester, every two weeks by the second trimester, and weekly by the third trimester. Some patients require even closer follow-up throughout pregnancy. (See 'Maternal and fetal monitoring' above.)

Patients with CKD are considered to be at high risk for preeclampsia. Low-dose aspirin therapy has been shown to decrease the risk of preeclampsia in women at moderate to high risk of the disease, but studies have not included patients with CKD. In pregnant patients with CKD, we weigh the potential risks and benefits of low-dose aspirin therapy and offer treatment to those without any contraindications to aspirin use. (See 'Prevention of preeclampsia' above.)

Vaginal delivery is the preferred mode of delivery if there are no obstetric contraindications. In most women, elective delivery is indicated if labor has not occurred by the estimated date of confinement. Even for low-risk women, there is little benefit in allowing the pregnancy to extend beyond this date, and maternal and/or perinatal risk may increase. We suggest scheduling delivery by 39 to 40 weeks of gestation if the patient or fetus does not have an indication for earlier delivery. Cesarean delivery is performed for standard obstetric indications. (See 'Delivery' above.)

Management of CKD should continue throughout pregnancy with ongoing attention to complications such as hypertension, metabolic bone disease, and anemia. If the estimated GFR (eGFR) declines below 20 mL/min/1.73 m2 or the blood urea nitrogen (BUN) increases >50 to 60 mg/dL (18 to 21 mmol/L), we consider the elective initiation of dialysis. This is different from the approach for nonpregnant CKD patients in whom there is no minimum eGFR or threshold BUN that provides an absolute indication to begin dialysis in the absence of symptoms. However, this decision must be individualized. (See 'Management of CKD during pregnancy' above.)

Significant potential complications specific to pregnant women with CKD include preeclampsia, gestational diabetes mellitus (GDM), and infection. The diagnosis of preeclampsia is challenging in this patient population because of preexisting proteinuria, reduced GFR, and hypertension. (See 'Maternal complications' above.)

Postpartum care is similar among women with and without CKD. There are no contraindications to breastfeeding among CKD patients. (See 'Postpartum care' above.)

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