Dialysis and Pregnancy

Diagnosis and maintenance of pregnancy

Given that most women with ESRD have hormonal imbalances, the diagnosis and maintenance of pregnancy is complex. Women with ESRD commonly have amenorrhea, nausea, vomiting, and increased levels of human chorionic gonadotropin, even without pregnancy. Pregnancy-associated plasma protein-A levels are higher in patients receiving hemodialysis, and levels are increased by the administration of heparin. These laboratory results raise concerns about false positive screening results for Down syndrome. Thus, to diagnose pregnancy and to assess fetal well-being, ultrasonography is considered the modality of choice.

Hemodialysis

A more intensive dialysis schedule is recommended, with BUN levels targeted to <16 to 18 mmol/L. This is usually achieved by increasing the frequency of HD sessions to five to seven per week, or switching to long nightly HD sessions, targeting a weekly Kt/V of 6 to 8. The target prescription for potassium is 3.5 to 4 meq/L; for sodium, 130 to 135 meq/L; for bicarbonate, 25; and calcium, 2.5.

Anticoagulation

We recommend the minimum required dose of heparin. Aspirin can be used for pre-eclampsia prophylaxis but needs to be stopped in the last few weeks of pregnancy during plans for surgery.

Peritoneal dialysis

Intensifying PD as pregnancy progresses, by decreasing volumes and increasing the number of cycles, is sufficient for most patients. Supplemental HD can be used. Icodextrin can be used when the benefits outweigh the risks (pregnancy category C).

Anemia

Anemia, which is common in both pregnancy and ESRD, is compounded in pregnant women receiving HD, whereas PD offers some advantage. The use of erythropoiesis-stimulating agents (ESA) to treat anemia (pregnancy category C) is required. There are case reports of darbepoetin being successfully used in pregnancy, with no obvious side effects. ESA dosing may need to be (twofold to threefold) higher in these patients. Vitamin B12 and folate replenishments are recommended. If the woman is iron deficient, intravenous iron sucrose (pregnancy category B) can be used. A target hemoglobin of 10 to 11 g/dL is ideal.

Bone mineral disease management

Sevelamer, lanthanum, aluminum, cinacalcet, and paricalcitol have not been well tested or established for use during pregnancy, but it is not anticipated that the woman will need these because of increased dialysis. There are case reports of successful outcomes with cinacalcet; however, more data are needed before recommendations can be made.

Phosphorus may need to be replenished, as may dialyzable multivitamins (vitamin C, thiamine, riboflavin, niacin, vitamin B6). Although it is quite unlikely, if the patient has elevated phosphorus, she can be safely treated with calcium-based binders throughout the pregnancy. Limited data are available regarding the use of other binders.

Vitamin D deficiency should be addressed. Calcitriol has been used in pregnancy, with additional calcium supplementation of 1.5 to 2 grams daily. The developing fetus requires approximately 30 grams of calcium for development. Although hypocalcemia is a concern, the patient should also be monitored for hypercalcemia, which can cause restricted development of the fetal parathyroid gland.

Nutrition

The pregnant woman with ESRD needs proper nutrition to support fetal development and maintain weight gain. Most dietary restrictions are relaxed because of intensified dialysis. A target protein intake of 1.5 to 1.8 g/kg of her prepregnancy weight per day + 20 g/day is recommended, with calories increased to 25 to 35 kcal/kg of pregnant weight per day.

Dry weight management

Dry weight management is complicated in most HD patients. The complexity increases when pregnancy weight gain must be factored into this equation. Ultrafiltration goals are usually relaxed to accommodate for weight gain. However, a close watch on BP and physical signs and symptoms must be kept because these patients are at risk of overloading rapidly. About 1 kilogram gain in weight is expected in the first trimester, followed by about 0.5 kilograms per week in the second and third trimesters. Avoiding large fluid removal is of paramount importance to prevent compromised uterine blood flow.

Hypertension

Hypertension is commonly associated with both pregnancy and ESRD. Severe hypertension is a significant concern for the health of the mother and the fetus. Medications should be reviewed if pregnancy is suspected. Many common medications used in ESRD, like angiotensin-converting enzyme and angiotensin receptor blockers, can be harmful if taken during pregnancy, although recent data show less risk in the first trimester. Antihypertensive agents found to be safe and effective for use during pregnancy include calcium channel blockers, labetalol, and methyldopa. Care should be taken to control BP yet prevent hypotension.

For patients with significantly elevated BP, complete blood count should be monitored for hemolytic anemia, thrombocytopenia, and elevated liver enzymes. The target for BP control is <140/90 mm Hg.

Diabetes management

A pregnant woman with chronic kidney disease is anticipated to have an increase in proteinuria. In addition, insulin use is recommended. The target for best glycemic control is hemoglobin A1c 7%. Close collaborative ties with an endocrinologist are highly recommended.

Immunosuppression in pregnancy and dialysis

Cyclosporine, tacrolimus, azathioprine, and prednisone are considered relatively safe during pregnancy, but immunosuppressants do cross the placental barrier. Their clinical significance in this setting is not well studied. Cyclosporine has been associated with prematurity and growth retardation, and tacrolimus has been associated with hyperkalemia and renal insufficiency in the fetus. Adrenal insufficiency and thymic hypoplasia have occasionally been described in the infants of transplant recipients, but these problems are unlikely if the dose of prednisone has been decreased to 15 mg. Mycophenolate mofetil and sirolimus are contraindicated in pregnancy. Cotreatment of such a high-risk patient by the obstetrician and the transplantation nephrologist is of paramount importance.

Obstetric care

These high-risk pregnancies with precious babies in health-compromised mothers need multispecialty dedicated care.

Diagnosing pre-eclampsia in anuric patients is challenging because neither proteinuria nor impaired renal function can be used as a means of diagnosis. Placental ultrasonography at about 22 weeks with uterine and umbilical Dopplers to assess placental size and morphology, and to quantify pulsatility indices, can be used. Abnormal pulsatility indices combined with fetal growth restriction indicate a diagnosis of pre-eclampsia. Although not widely available, antiangiogenic and angiogenic factor measurements, including soluble FMS-like tyrosine kinase and placental growth factor, may be used to aid in the diagnosis of pre-eclampsia. The use of magnesium for treatment will require caution because of its possible toxicity.

Cervical cerclage may be required to treat early cervical incompetence and prevent preterm birth. The reasons for this are unclear. Planned delivery (preferably vaginal if possible) at about 37 weeks is best. Postdelivery monitoring of the neonate for at least 48 hours is usual care.

Breastfeeding

The benefit of breastfeeding supersedes the associated risks. Significantly higher levels of creatinine, urea, and uric acid were found in pre-HD breast milk than in post-HD milk. Sodium and chloride were significantly increased in post-HD samples. Phosphate was significantly lower in pre-HD and post-HD breast milk than in milk from control women (low-risk mothers matched for postpartum age), whereas calcium showed no significant differences. In terms of nutrient components, glucose levels were decreased, whereas protein, triglycerides, cholesterol, and immunoglobulins were similar to control milk and were not affected by dialysis. Similarly, no significant differences were found in iron, potassium, and magnesium content. Thus overall, there was a high similarity of breast milk samples from HD patients to samples from low-risk control mothers. The significant variations in breast milk composition between pre-HD and post-HD samples suggest that breastfeeding after a dialysis session is preferable to breastfeeding beforehand. The authors of that study suggested that the mother discard milk pumped immediately before dialysis.

We could not find any data on women receiving PD; however, we assume that similar changes can be expected but without major variations because of the continuous nature of PD. Lactation-safe medications for hypertension and comorbid conditions will be needed; they include methyldopa, labetalol, and nifedipine. Methyldopa, though the best recommended for this period, does have the potential of causing further depression in the mothers, who are already in a high-stress situation. Angiotensin-converting enzyme inhibitors, including captopril and enalapril, are secreted in low amounts in breast milk and may be used if needed, with close assessment of neonates for hypotension. Aggressive ultrafiltration may reduce the milk supply. Avoiding heparin that contains the preservative benzyl alcohol is prudent because it is potentially toxic to at-risk infants.

Emotional support

Through all this, it is evident that mothers with ESRD face multiple extremely stressful challenges. Difficulty in conception, difficulty in maintaining pregnancy, and the need to care for a child by a patient who is already struggling for her own survival on dialysis require major coping skills. Postpartum depression should be expected. The role of follow-up emotional supportive care and mental health counseling cannot be emphasized enough. However, data are strikingly lacking in this area.