Drug
Pregnancy implication
Lactation consideration
Risks
Selective use allowed during pregnancy
Glucocorticoids (e.g., prednisone)
Prednisone is suggested at the lowest possible dose to control the disease (less than 10 mg/day)
If possible, avoid glucocorticoids in the first trimester when the hard palate is forming
It is advisable to discard breast milk for the first 4 h after a dose of prednisone ≥20 mg. Glucocorticoids are excreted into the breast milk, but their use is compatible according to the American Academy of Pediatrics (AAP)
Glucocorticoid use during the first trimester has been associated with cleft lip and occurs in approximately 1.7 in 1000 live births
Glucocorticoid use during pregnancy may increase the risk of premature rupture of the membranes (PROM) and intrauterine growth restriction
Azathioprine (AZA) and 6-mercaptopurine (6-MP)
AZA may be safer than other immunosuppressive agents and is preferred over cyclophosphamide, cyclosporine, and mycophenolate mofetil. Doses should not exceed 2 mg/kg/day
AZA and 6-MP are excreted in the breast milk and should not be used in women who are breastfeeding. The potential benefits of breastfeeding should be weighed against the potential risks of the drug
In a study of AZA use in pregnant transplant recipient’s low birth weights, prematurity, jaundice, respiratory distress syndrome, and aspiration occurred significantly more frequently in the AZA group. Two retrospective studies of pregnant patients with IBD showed no significance in regard to fertility, birth defects, infections, and maternal malignancies in the AZA or 6-MP group
Cyclosporine
For lupus nephritis, other agents are recommended. When necessary, cyclosporine should be administered at the minimum dose, and the maternal blood pressure and renal function should be monitored closely
Cyclosporine is excreted in breast milk and so should not be taken by breastfeeding women
Cyclosporine crosses the placenta and may be detected in the serum of newborns for several days after birth
Tacrolimus
Tacrolimus is a reasonable alternative to more aggressive immunosuppressive agents during pregnancy. When necessary, the minimum dose should be used, and blood pressure and renal function should be monitored closely
Tacrolimus is generally not recommended for breastfeeding women; however data shows that the maximal dose infants received from nursing mothers is 0.02–0.5 percent which suggests that it may be compatible
Tacrolimus crosses the human placenta, and its levels are measurable in the cord blood, amniotic fluid, and newborn serum. In a study of 100 pregnant women on tacrolimus, 60% of live births were premature, and 4 babies had malformations
Moderate to high risk of fetal harm
Cyclophosphamide (CYC)
It is strongly recommended to avoid cyclophosphamide during pregnancy except in life-threatening medical conditions where no alternative therapy is available
Cyclophosphamide is excreted in breast milk, and so it should not be taken by breastfeeding women
Cyclophosphamide crosses the placenta and can be detected in amniotic fluid. In animal studies, congenital anomalies such as exophthalmos, cleft palate, skeletal abnormalities, fetal resorption, and growth retardation were demonstrated. The risk of embryo toxicity is highest during the first trimester, and better outcomes are seen in the second or third trimester
Mycophenolate mofetil (MMF)
There is a US boxed warning regarding embryo-fetal toxicity with mycophenolate use. For women with lupus nephritis taking mycophenolate and planning a pregnancy, mycophenolate should be discontinued at least 6 weeks prior to trying to conceive
Mycophenolate is excreted in breast milk, and so should not be taken by breastfeeding women
Mycophenolate exposure during pregnancy is associated with increased risk of congenital malformations including external ear abnormalities, cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. Spontaneous abortions have also been reported
Abatacept
Avoid abatacept during pregnancy and lactation unless the mother’s health is highly dependent on this medication
There is insufficient data to address the issue of safety for breastfed infants. It is recommended to avoid breastfeeding during treatment unless no other medication can control the disease
Information related to the use of abatacept in pregnancy is limited. Adverse effects were not observed in animal studies. There are no adequate studies of its effects on human pregnancies
Rituximab
Avoid rituximab during pregnancy and lactation unless the mother’s health is critically dependent on this medication
There is insufficient data to address the issue of safety for breastfed infants. Human IgG is excreted in breast milk, and therefore, rituximab may also be excreted in milk
Rituximab has been detected in high concentrations in umbilical cord blood. In animal reproduction studies, adverse effects have been demonstrated including reversible decrease of B cells and immunosuppression
Electrolyte Disorders During Pregnancy
How Can Pregnancy Cause Electrolyte Imbalances?
Morning sickness is a common issue in pregnancy and includes symptoms of vomiting, diaphoresis, and frequent urination which increase water and electrolyte loss. In addition, nausea prevents pregnant patients from hydrating properly which can make it more difficult to replace lost nutrients, fluids, or electrolytes [1, 2, 10–12].
Diarrhea during pregnancy can be caused by sudden dietary changes, increased hormone production, or sensitivity to certain foods that some women can experience during pregnancy. Diarrhea results in water and electrolyte loss, and if excessive, women can become dehydrated. In addition, the body’s increased water needs add to the challenge of maintaining hydration. For example, a majority of the maternal weight is water. Normally, there is about 5–6 l of water in the body; during pregnancy, this can increase to as much as 9 l. Blood volume expands by up to 50 percent during pregnancy; therefore a pregnant woman will need slightly more electrolytes to keep the extra fluid in the right chemical balance.
Calcium
Calcium is the most abundant mineral in the body and is essential for many diverse processes, including bone formation, muscle contraction, and enzyme and hormone functioning.
A dietary intake of 1200 mg/day of oral calcium for pregnant women is recommended by the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations.
Suggested calcium supplementation in pregnant women
Dosage | 1.5–2.0 g oral calcium/day |
Frequency | Daily, with the total daily dosage divided into three doses (preferably taken at mealtimes) |
Duration | From 20 weeks’ gestation until the end of pregnancy |
Target group | All pregnant women, particularly those at higher risk of gestational hypertension and preeclampsia (Risk factors: obesity, previous preeclampsia, diabetes, chronic hypertension, renal disease, autoimmune disease, nulliparity, advanced maternal age, and adolescent pregnancy) |
In a Cochrane review, calcium supplementation (≥1 g/day) is associated with a significant reduction in the risk of preeclampsia, particularly for women with low-calcium diets. It also reduced preterm birth and the occurrence of maternal death. Excessive consumption of calcium may increase the risk of urinary stones and urinary tract infection and reduce the absorption of other essential micronutrients.
Magnesium
Magnesium is an essential mineral required for regulation of body temperature, nucleic acid, and protein synthesis and in maintaining nerve and muscle cell electrical potentials. Magnesium is present in many foods: Dairy products, bread and cereal, legumes, vegetables, and meats are all good sources of magnesium.
Common causes of magnesium deficiency include inadequate dietary intake and/or gastrointestinal absorption, increased losses through the gastrointestinal or renal systems, and increased requirement for magnesium, such as pregnancy.
Magnesium level is known to decline during pregnancy. However, magnesium supplementation is not needed in these patients after a series of studies. A Cochrane review indicated no statistically significant effects of magnesium supplementation on the frequency of perinatal mortality or small-for-gestational-age infants when compared with placebo or no treatment. The review also showed that magnesium supplementation during pregnancy had no significant effect on preeclampsia; maternal deaths were not reported by the included trials.
Potassium
Potassium has a vital role in the proper functioning of nerve and muscle cells. The kidneys play an important role in regulating potassium level in the blood stream by eliminating excess potassium through urine. The normal levels of potassium in the blood stream are 3.5–5 mmol/L. Anything below this level is considered hypokalemia.
Hypokalemic periodic paralysis is a situation that may arise during pregnancy due to the extreme muscle weakness. This temporary paralysis more often affects arms and legs.
Hypokalemia can cause the cardiac complication known as cardiac dysrhythmias (irregular heartbeats). Severe dysrhythmias can cause cardiac arrest and lung paralysis.
Untreated hypokalemia can put both mother and fetus in danger.
Mild symptoms: constipation, muscle cramps, fatigue and numbness, nausea and vomiting, and abdominal cramping and bloating
Severe symptoms: irregular heartbeats, passing large amount of urine, feeling thirsty, and breathing problems
Vomiting and diarrhea during pregnancy.
Diuretic usage.
Increased level of aldosterone: Aldosterone is a steroid hormone secreted by adrenal gland. During pregnancy, this hormone is produced in higher levels and can result in loss of potassium through urine.
Potassium chloride formulations in pregnancy
Formulations | Dosing | Pregnancy considerations | |
|---|---|---|---|
Potassium chloride | Oral (tablet, capsule, liquid, packet), IV ∗750 mg potassium chloride = elemental potassium 390 mg = potassium 10 mEq = potassium 10 mmol | 1–2 mEq/kg/day in 1–2 divided doses Pregnant and nonpregnant women: 4700 mg per day Breastfeeding women: 5100 mg per day | Category C Reproductive studies have not been conducted. Potassium requirements are the same in pregnant and nonpregnant women Adverse events have not been observed following use of potassium supplements in healthy women with normal pregnancies Use caution in pregnant women with other medical conditions (e.g., preeclampsia; may be more likely to develop hyperkalemia) |
Endocrine Manifestations of Chronic Kidney Disease
Diabetes in CKD
Chronic kidney disease (CKD) is associated with insulin resistance and decreased insulin degradation [1, 2, 12–14].
Hemoglobin A1c levels are used to monitor for hyperglycemia in all patients with diabetes and CKD or ESRD, although HbA1c may not be as accurate among ESRD patients as in the general population. For most predialysis CKD patients, it is suggested using an HbA1c goal of approximately 7%, rather than lower values. The HbA1c goal depends upon the age of the patients, the risk of hypoglycemia, and upon other comorbid conditions.
Metformin should not be used among CKD patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73, because of an increased risk of lactic acidosis.
Patients who fail therapy with oral agents are treated with insulin. Among patients who are treated with insulin, the starting dose of insulin may need to be lower than would ordinarily be used for patients with normal kidney function.
Several different insulin regimens can be used to achieve glycemic control. Examples include twice-daily intermediate-acting insulin, with regular insulin given before breakfast and before supper, or long-acting insulin, with two or three times daily supplemental regular insulin, given two to three times per day before meals.
The initial dose of insulin should be decreased by approximately 50 percent.
Some clinicians prefer to use oral agents rather than insulin, especially among patients who have already achieved acceptable glycemic control on these agents. If an oral agent is used, the preferred agents are glipizide and repaglinide.
For peritoneal dialysis patients with type 2 diabetes who were already on an oral agent with good glycemic control prior to starting dialysis and for patients who develop diabetes after starting dialysis, it is suggested using an oral agent with glipizide or repaglinide, rather than insulin.
Instead of fluid replacement, management is principally dependent upon the administration of low doses of intravenous insulin.
Diabetes in Pregnancy
Poorly controlled diabetes can cause fetal malformations, fetal loss, and maternal morbidity. Women with diabetes should use effective contraception until optimal glycemic control is achieved before attempting pregnancy. Diabetic retinopathy may worsen, hypertension may develop, and renal function may deteriorate during pregnancy, requiring enhanced monitoring for these issues.
Glycemic control can change dramatically during pregnancy; thus frequent adjustment to management may be needed. Once pregnancy is established, glucose control should be managed more aggressively than in the nonpregnant state. Self-monitored blood glucose should occur before and after meals, with occasional early morning (i.e., 2–4 am) measurement.
For patients with type 1 and type 2 diabetes, insulin is the drug treatment of choice. Women receiving insulin glargine should be switched to detemir or NPH insulin. Glyburide and metformin may be alternatives, but are not recommended by the American Diabetes Association.
Renal Transplant Pharmacotherapy During Pregnancy
Renal transplant pharmacotherapy during pregnancy
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