PG Classroom - CME: Renal Disease and Pregnancy

INTRODUCTION   

Physiologic changes occurring in pregnancy involve nearly every organ system, and the kidneys are no exception. This article focuses not only on renal diseases that occur in pregnancy but also on how pregnancy affects chronic renal diseases. Patients with end-stage renal disease (ESRD) requiring renal replacement therapy and patients after renal transplantation pose additional interesting scenarios and possible complications. This subject is quite vast and the authors believe it important to ask two questions in the setting of pregnancy and renal disease: How does pregnancy affect kidney disease? How does kidney disease affect pregnancy?

RENAL FUNCTION DURING PREGNANCY

The renal system undergoes monumental physiologic and anatomic changes during a normal pregnancy. An understanding of these changes is necessary in order to further understand how they may lead to or worsen renal disease.

Renal plasma flow increases by 50-70% in pregnancy, and this change is most pronounced in the first two trimesters. This is one of the factors that lead to an increased glomerular filtration rate (GFR). The GFR peaks around the 13th week of pregnancy and can reach levels up to 150% of normal. Therefore, both BUN and creatinine levels, the plasma markers of GFR, are decreased. This decrease has clinical significance in that a normal BUN or creatinine level in a pregnant female may actually indicate underlying renal disease.

Similarly, in the initial part of pregnancy, increased levels of progesterone enhance relaxation of the arterial smooth muscles and thus decrease peripheral vascular resistance. Therefore, a blood pressure fall of approximately 10 mm Hg occurs in the first 24 weeks of pregnancy. The blood pressure gradually returns to a prepregnancy level by term; thus, a consistent normal or prepregnancy blood pressure may suggest the presence of a condition that predisposes patients to hypertension.

A change in tubular function with increased glucosuria also occurs. In addition, a reset in the osmostat occurs, resulting in increased thirst and decreased serum sodium levels (by approximately 5 mEq/L) compared with nonpregnant females. Effects of progesterone also result in a state of mild respiratory alkalosis and a blood gas of 7.44/30 pCO2/HCO322 is representative.

The anatomic changes are primarily in the collecting system. A dilatation of the ureters and pelvis occurs and is presumed to be secondary to the smooth muscle–relaxing effect of progesterone. This dilatation is often more pronounced on the right secondary to dextrorotation of the uterus and dilatation of the right ovarian venous plexus. This can lead to urinary stasis and, as discussed later, an increased risk of developing urinary tract infections (UTIs). There is also an increase in overall kidney size by about 1-1.5 cm.

As a rule, all the physiologic changes maximize by the end of the second trimester and then start to return to the prepartum level, whereas changes in the anatomy take up to 3 months postpartum to subside.

RENAL DISEASE OCCURRING DURING PREGNANCY  

Urinary tract infections

UTIs are the most common renal disease occurring during pregnancy and range from asymptomatic bacteriuria to pyelonephritis. UTIs have been associated with small for gestational age (SGA) babies, premature labor, and intrauterine fetal death.

Pregnant females are at increased risk for development of UTIs, primarily because of the anatomic and physiologic changes that occur in normal pregnancy. As mentioned previously, the collecting system is dilated during pregnancy, most likely secondary to the smooth muscle–relaxing properties of progesterone. This dilatation almost always resolves 2-4 days after delivery. In addition, increased vesicoureteral reflux occurs.

  • Asymptomatic bacteriuria

    • Aggressively treat asymptomatic bacteriuria with oral antibiotics. A clean-voided specimen containing more than 100,000 organisms per milliliter is considered evidence for infection.

    • Up to 30% of patients develop pyelonephritis if asymptomatic bacteriuria is left untreated.

    • Treatment with a 10-day course of oral antibiotics is warranted and reduces the incidence of pyelonephritis to approximately 3%.

    • Effective therapies include nitrofurantoin, ampicillin, amoxicillin, or sulfonamides.

    • Urinalysis with culture should be performed and evaluated on a monthly basis after resolution.

    • If bacteriuria is persistent, suppressive therapy is probably indicated. Nitrofurantoin (100 mg at night) is a proven effective suppressive treatment.

  • Cystitis

    • Cystitis is associated with symptoms of dysuria, urgency, and frequency, usually without systemic signs.

    • Aggressively treat cystitis with oral antibiotic regimens.

    • Keep in mind that symptoms of cystitis and pyuria accompanied by a "sterile" urine culture finding may be the consequence of urethritis caused by Chlamydia trachomatis, a common pathogen of the genitourinary tract.

    • Mucopurulent cervicitis usually coexists, and erythromycin therapy may be effective.

  • Pyelonephritis

    • Pyelonephritis, a bacterial infection of the kidneys, occurs in up to 2% of pregnant women. Onset is usually abrupt and is characterized by fevers, chills, flank pain, anorexia, nausea, and vomiting. Costovertebral tenderness can usually be elicited by physical examination.

    • The most likely etiologic organisms include Escherichia coli and Klebsiella, Enterobacter, and Proteus species.

    • Up to 15% of patients have concurrent bacteremia. Complications other than bacteremia include hemolysis, sepsis, adult respiratory distress syndrome, and death.

    • Pyelonephritis requires hospitalization and administration of intravenous antibiotics and intravenous fluid administration. Continue treatment with intravenous antibiotics until fever resolves. Effective regimens include ampicillin plus gentamicin or a third-generation cephalosporin. Continue oral administration of antibiotics and suppressive therapy throughout the pregnancy.

Hypertension

A variety of hypertensive disorders can occur in pregnancy. Terminology varies according to source, but the authors use the system recommended by the National High Blood Pressure Education Program, which describes the following 5 entities (NHBPEP, 2000):

  • Gestational hypertension

    • Gestational hypertension is defined as blood pressure of 140/90 mm Hg or greater with no episodes of hypertension before pregnancy.

    • Transient hypertension is a term used to describe gestational hypertension in which preeclampsia does not develop, with blood pressure returning to normal levels within 12 weeks postpartum.

    • Proteinuria usually does not occur, although it is a sign of worsening disease if present.

    • Patients with gestational hypertension are usually asymptomatic, but they may have symptoms or signs similar to preeclampsia (abdominal pain, thrombocytopenia). This type of hypertension usually affects nulliparous females.

    • This phenomenon of transient hypertension of pregnancy is actually a retrospective diagnosis and is confused with preeclampsia at the time of onset and with essential hypertension postpartum until the blood pressure returns to normal. It is actually prudent to manage it as preeclampsia when first diagnosed. There have been studies that have followed patients found to have isolated elevated blood pressure readings during pregnancy and the earlier such a high reading is observed after 20 weeks of gestation, the more likely it will evolve into preeclampsia.

    • Gestational hypertension usually occurs in the third trimester and may predict the development of hypertension later in life.

  • Chronic hypertension

    • Chronic hypertension is associated with underlying or preexisting hypertension. The diagnosis is usually established by a blood pressure of 140/90 mm Hg or greater before pregnancy or before 20 weeks' gestation, or by persistent hypertension long after delivery.

    • This diagnosis can be difficult to make, especially if no prior blood pressure readings are available or if the patient is not seen until late in pregnancy.

    • Complications of chronic hypertension include (but are not limited to) ventricular hypertrophy with congestive heart failure, risk of cerebrovascular accidents, superimposed preeclampsia, and an increased risk in the incidence of abruptio placenta, growth restriction, and fetal death.

  • Preeclampsia

    • Preeclampsia is a more severe disease of pregnancy that includes a triad of hypertension, edema, and proteinuria. It is one of the leading causes of maternal morbidity and mortality as well as adverse outcomes in the fetus. Preeclampsia has often been dubbed the disease of theories because physicians and epidemiologists could not point to a concrete pathogenic mechanism for the disease. However, there has been a recent revival in the research for identifying causative factors and for identifying clinically applicable diagnostic screening tests for this fascinating disease.

    • Pathophysiology

      • Utero-placental ischemia: A combination of genetic and environmental factors is thought to result in inadequate invasion of the uterine spiral arteries by the placental trophoblasts. There is a resulting inability of the uterine vessels to transform from low-caliber resistive channels to a high-caliber capacitance system. This results in utero-placental ischemia that then results in generalized endothelial dysfunction.

      • Generalized endothelial dysfunction: The utero-placental ischemia, mentioned above, results in oxidative stress for the release of a soluble cytokine, the sFlt-1 (soluble fms-like tyrosine kinase-1), and a decrease in placental growth factor (PIGF) and vascular endothelial growth factor (VEGF). There is a resultant antiangiogenesis balance in the body that causes the widespread endothelial dysfunction and microvascular compromise that is the hallmark of this disease.

    • Screening tests

      • Screening tests have traditionally been epidemiological and helped to identify non-modifiable risk factors.

      • Many clinical tests proposed (e.g., hyperinsulinemia, decreased urinary calcium excretion, sensitivity to angiotensin) lack clinically applicable predictive values.

      • Recently, urinary PlGF values and sFlt-1 values have shown great promise as a means of identifying preclinical preeclampsia and appear to be tied very well to the actual pathogenesis of the disease, as explained above.

    • Symptoms often include epigastric or right upper quadrant pain. This pain may be secondary to hepatic ischemia and edema leading to stretching of the Glisson capsule.

    • Proteinuria is an important sign and is defined as greater than 300 mg of protein in a 24-hour urine collection or persistent random urine samples of more than 30 mg/dL.

    • Additional laboratory data may reveal thrombocytopenia, likely secondary to platelet activation and aggregation in the microvasculature.

    • Schistocytes and anemia may be present in more severe disease, thus indicating microangiopathic hemolytic anemia.

    • With regard to the kidneys, a decrease in the GFR occurs secondary to intrarenal vasospasm. This may manifest as a "prerenal" picture. Acute renal failure (ARF) may develop, and acute tubular necrosis (ATN) may ensue if this hypoperfusion persists.

    • HELLP syndrome (Hemolysis, Elevated liver enzymes, and Low Platelets) is observed when severe preeclampsia or eclampsia is accompanied by significant liver involvement.

    • The following risk factors are associated with the development of preeclampsia:

      • Age older than 35 years

      • Age younger than 16 years

      • First pregnancy

      • Multiple pregnancies

      • History of chronic hypertension

      • Obesity

      • African American race

  • Eclampsia

    • Eclampsia is essentially the occurrence of seizure activity with no other explainable cause in the setting of preeclampsia.

    • The condition can largely be prevented with appropriate prenatal care.

  • Preeclampsia superimposed on chronic hypertension

    • Generally, this condition is defined as new-onset proteinuria (ie, >300 mg/d) after 20 weeks' gestation in a hypertensive patient or as a sudden increase in proteinuria or blood pressure in a patient with hypertension and proteinuria before 20 weeks' gestation.

    • This type of preeclampsia tends to be severe.

Management of hypertension

Much attention has been given to the management of these patients. Nonpharmacologic treatments include bed rest and alcohol avoidance. Weight loss and salt restriction are not recommended.

  • ACE inhibitors are contraindicated because they are associated with oligohydramnios and patent ductus arteriosis. Oligohydramnios can lead to pulmonary hypoplasia, respiratory failure, and neonatal death. In addition, limb contractures and abnormal fetal skull calcifications are associated with oligohydramnios. No risks have been shown if used in the first trimester, although patients using ACE inhibitors at the time of pregnancy should have their regimen promptly changed.

  • Diuretics are generally avoided during pregnancy because they may lead to intravascular volume depletion and organ hypoperfusion. More importantly, diuretics cause placental hypoperfusion. They are used with caution in patients with significant edema. However, if preeclampsia develops, diuretics must be promptly discontinued.

  • Beta-blockers have no major contraindications, although neonatal bradycardia, hypoglycemia, and respiratory depression are of concern. These adverse effects are generally easily treated. Labetalol is not associated with neonatal bradycardia and is being used with increasing frequency, especially for hypertensive emergencies.

  • Alpha-methyldopa, a centrally acting agent, has long been the drug of choice for essential hypertension. Clonidine (another centrally acting agent) is also used.

  • Calcium channel blockers are being used with increasing frequency; however, they are generally limited to severe hypertension that is unresponsive to other medications. Calcium channel blockers may cause tocolysis in the third trimester. Congenital abnormalities are not associated with their use.

  • Hydralazine, an arterial vasodilator, is a commonly used drug and is a first-line agent for hypertensive emergencies. For essential hypertension, it is generally reserved as a second- or third-line agent.

  • Experience with the use of minoxidil and prazosin is limited. Minoxidil has been associated with congenital abnormalities in one case report.

Management of preeclampsia

The goals of management are termination of the pregnancy with minimal trauma to the mother and the fetus, infant survival, and restoration of health to the mother. A rise of blood pressure of 10 mm Hg or more should prompt hospitalization and attempts to prevent preeclampsia, which requires well-controlled blood pressure in a hypertensive mother.

  • Several prevention strategies have been evaluated, including dietary (eg, calcium supplementation, fish oils, sodium restriction) and medical (eg, low-dose aspirin, antioxidants). These treatments have not been shown to definitively decrease the incidence of preeclampsia.

  • Basic management includes early prenatal detection and accurate knowledge of the age of the fetus. Maintain a low threshold for hospital admission, especially if worsening hypertension or proteinuria is present. Hospitalization should include serial blood pressure measurements and weight determination. A 24-hour urinary protein excretion rate should be quantitated as well as CBC counts and BUN and creatinine levels. Liver enzyme levels should be determined.

  • In mild preeclampsia, physical activity should be significantly reduced. Close monitoring is essential, not only for the possibility of worsening symptoms, but also for the condition of the cervix and the duration of gestation. Many patients can be monitored until the onset of labor.

  • If eclampsia is severe or if symptoms worsen (eg, headache, visual disturbances, epigastric pain, oliguria), it can be assumed that eclampsia (seizures) is imminent, and the pregnancy must be terminated.

Acute renal failure

Acute renal failure in pregnancy follows a bimodal distribution. There are peaks in the first trimester (related to unregulated and/or septic abortion) and the late third trimester (related to obstetric complications). The incidence of ARF due to sepsis has fallen significantly in the last 30 years relative to the incidence secondary to obstetric complications (e.g., abruptio placenta, amniotic fluid embolism, postpartum hemorrhage).

ARF is conventionally and conveniently divided into 3 categories: prerenal, intrinsic (or "renal"), and postrenal. Sepsis secondary to illegal abortion, while now less common in industrialized nations, is still a common cause of renal failure worldwide. Milder forms of ARF are observed in industrialized countries, and only about 1 case in 15,000 pregnancies requires dialysis.

  • Prerenal

    • Prerenal causes include the following hypovolemic states:

      • Hemorrhage

      • Volume depletion from GI or renal losses, burns, fluid sequestration, or low cardiac output states (e.g., chronic heart failure and other diseases of myocardium, valvulopathy, arrhythmia, pericardial diseases, tamponade)

      • Systemic vasodilatation (e.g., sepsis, anaphylaxis)

      • Disseminated intravascular coagulation

    • Sepsis from illegal abortions is often due to Clostridium welchii.

  • Renal

    • Acute tubular necrosis

      • ATN is the most common pathologic finding for ARF in pregnancy.

      • ATN typically occurs after an acute ischemic or toxic event.

      • Ischemic ATN is often considered to be a continuum of prerenal azotemia. Indeed, the causes of the two conditions are identical. In pregnancy, these causes are often related to hemorrhage, abruptio placenta, amniotic fluid embolism, and retained dead fetus.

      • In addition, nephrotoxic medications are implicated. Remember that gentamicin is occasionally administered in pregnancy, especially in pyelonephritis.

    • Cortical necrosis

      • The presentation of cortical necrosis is similar to that of ATN and is differentiated only by arteriogram and/or biopsy. It was a common finding in ARF because of septic abortion.

      • No specific treatment for cortical necrosis is available, so these tests may not be necessary other than for prognostic value.

    • Thrombotic microangiopathies

      • Both TTP and HUS can be seen in pregnancy. Incidence of HUS is actually increased in pregnancy, whereas TTP remains the same. Both of these microangiopathies need to be distinguished from HELLP syndrome.

      • Plasma exchange is required for both TTP and HUS.

    • Postrenal

      • Postrenal causes, i.e., obstructions, are rare but must be considered in all patients with ARF because of the ease of reversibility. Diagnosis, however, may be difficult.

      • The collecting system undergoes a physiologic dilatation secondary to the smooth muscle–relaxing effects of progesterone. Therefore, ultrasound, which relies heavily on visualization of the dilated collecting system for the diagnosis of obstruction, may be difficult to interpret.

      • Use of intravenous or retrograde pyelography may be necessary, realizing that this modality exposes the fetus to radiation.

    • Dialysis-requiring ARF

      • Renal failure severe enough to warrant dialysis usually also warrants termination of pregnancy.

      • If subacute and if the fetus is still viable, an early initiation (approximately BUN 50) is preferred to prevent uremic insult to the fetus.

In an effort to prevent dialysis-related hypotension, frequent HD sessions (5-7 sessions/wk) are scheduled.    

PREGNANCY IN PREEXISTING RENAL DISEASE            

Historically, pregnancy has been commonly regarded as very high risk to the female with chronic renal disease. Attempts have been made to clarify these risks in the settings of chronic renal insufficiency, dialysis, and transplanted kidneys.

In general, patients receiving dialysis have a marked decrease in fertility, yet pregnancy occasionally occurs. Certainly, a return of fertility in transplant recipients is the rule. These transplant patients have other special considerations, including the use of immunosuppressive medications and the risk of opportunistic infections.

The following discussion addresses pregnancy as it affects patients with chronic renal insufficiency, those with ESRD requiring dialysis, and those who have received a renal transplant. Keep in mind the effects of pregnancy on kidneys and the effects of kidney disease on pregnancy.

Chronic renal insufficiency

The concerns of pregnancy with chronic renal insufficiency are twofold. First, the effects of the pregnancy on renal function must be considered. Second, the effects of the renal insufficiency on the pregnancy are a concern.

Effect of pregnancy on renal function

Accelerated deterioration of renal function occurs in some patients with chronic renal insufficiency. In general, however, the prognosis depends on the degree of renal dysfunction at the time of conception as well as the presence and extent of comorbidities, specifically, hypertension and proteinuria. Renal function is most likely preserved, especially with mild renal insufficiency.

Katz et al found that 16% of pregnant patients with mild renal insufficiency (serum creatinine level, <1.5 mg/dL) had a decline in renal function. About 6% of these patients progressed to peripartum ESRD. Cunningham et al found that patients with moderate or severe renal insufficiency were much more likely to have accelerated renal impairment. About 20% of pregnant patients with moderate renal insufficiency (serum creatinine level, 1.5-2.4 mg/dL) progressed to ESRD. Severe renal insufficiency (serum creatinine level, >2.5 mg/dL) progressed to ESRD within a year after delivery in 45% of patients.

The cause of accelerated renal impairment in some pregnant patients is not entirely clear. Worsening hypertension is certainly a poor prognostic indicator and is probably a direct contributor to worsening renal function. UTIs are common and also probably trigger a decline. Some evidence suggests that proteinuria, which almost always increases in pregnancy with any underlying renal impairment, may have a detrimental effect on the kidneys.

With the exception of lupus nephritis, the etiology of the renal insufficiency seems irrelevant with regard to prognosis in pregnancy. It was previously believed that diabetic nephropathy did not appear to worsen during pregnancy. Recently, it has been shown that diabetic nephropathy has accelerated progression in 45% of patients. Again, as in other causes of renal insufficiency, the level of renal impairment at the time of conception is the most important determinant of the effect of pregnancy on the progression of disease.

As mentioned previously, lupus nephritis is a special consideration. This is a common cause of renal insufficiency in women of childbearing age. Exacerbations (flares) increase the risk of renal failure. Approximately half of patients experience an exacerbation of lupus during pregnancy, although it is much less common in patients who have been in remission for more than 6 months. Fetal loss occurs in up to 50% of patients.

The presence of lupus anticoagulant and the anticardiolipin antibody increases the risk; therefore, screen all lupus patients for these antibodies. Prior to 34 weeks' gestation, a therapeutic abortion is generally recommended if a lupus flare is associated with worsening renal function or worsening hypertension. Delivery is recommended after 34 weeks' gestation. Monitor the infant for neonatal lupus, specifically for rash, thrombocytopenia, and congenital heart block.

Treatment for lupus flares includes prednisone or azathioprine. Cyclophosphamide is avoided because it is teratogenic in the first trimester, and it may cause bone marrow suppression in the child. Prednisone, although usually well tolerated, may worsen hypertension and lead to further complications.

Effect of renal insufficiency on pregnancy

In general, fetal survival rates are good, approaching 95% in most studies. Hou suggests, however, that the success rate of pregnancy is no better than 52% in dialysis patients. Complications, including SGA infants, preterm labor, and stillbirth, are increased even in mild renal insufficiency. Factors associated with increased perinatal mortality and preterm labor was impaired renal function, early or severe hypertension, and nephrotic-range proteinuria.

Management

Prenatal visits should be frequent. Some authorities suggest visits every 2 weeks until 28 weeks' gestation and then weekly. Counseling of the risk of worsening renal impairment is important. Check blood pressure at every visit. Measure protein excretion, usually by dipstick. If any worsening proteinuria is discovered, obtain a 24-urine collection. Perform screening for asymptomatic bacteriuria, and treat it aggressively. Erythropoietin has been used for anemia but should be used with caution because it can worsen hypertension.

Pregnancy in patients receiving dialysis

ESRD requiring dialysis is associated with a marked decrease in fertility. Pregnancy, however, occurs in approximately 1% of patients, usually within the first few years of starting dialysis. The cause of infertility is not entirely clear but is probably multifactorial. It has been estimated that up to 42% of women receiving dialysis who are of childbearing age have regular menses, but many more are likely anovulatory. Anemia probably also plays a role. In fact, some investigators suggest that the regular use of erythropoietin improves the pregnancy rate.

In general, however, pregnancy is a contraindication while on dialysis. The fetal outcome is quite poor. Only 23-55% of pregnancies result in surviving infants, and a large number of second-trimester spontaneous abortions occur. In addition, surviving infants have significant morbidities. Approximately 85% of surviving infants are born premature, and 28% are born SGA. Maternal complications occur as well. Several maternal deaths have been reported. Hypertension worsens in more than 80% of pregnant females on dialysis and is a major concern.

The diagnosis of pregnancy is also difficult because levels of beta-human chorionic gonadotropin (beta-hCG) are normally elevated in patients receiving dialysis. If pregnancy is considered likely and the beta-hCG level is high, obtain an ultrasound to aid in diagnosis.

Some general recommendations apply to patients who become pregnant while receiving dialysis. Place the patient on a transplant list (if not on already) because outcomes with allograft transplant patients are markedly better. During hemodialysis, pursue uterine and fetal monitoring and make every attempt to avoid dialysis-induced hypotension. Some evidence indicates that judicious use of erythropoietin may improve fetal survival; however, no findings from randomized studies support this. Erythropoietin can also increase hypertension and must be used cautiously. Increased frequency of dialysis may improve mortality and morbidity. Aggressive dialysis to keep BUN levels less than 50 mg/dL may be pursued with daily dialysis. Controlling uremia in this fashion may avoid polyhydramnios, control hypertension, and improve the mother's nutritional status.

Pregnancy in patients after transplantation

In general, a return of fertility is the rule in female transplant patients of childbearing age. In fact, pregnancy occurs in up to 12% of these patients. Pregnancy success rates are also quite good, with greater than 90% fetal survival rates after the first trimester. In the appropriate setting, pregnancy can be anticipated, planned, and even encouraged.

As with patients with chronic renal insufficiency, factors such as uncontrolled or worsening hypertension, worsening proteinuria, and poor prepregnancy renal function are important prognostic indicators for the risk of renal function deterioration. Whether pregnancy itself induces a significant risk to the transplanted kidney's function is unclear. Obstruction of the transplant ureter by the pregnant uterus is quite rare but has been reported. Further long-term studies are indicated. Current opinion holds that the graft function is not adversely affected by pregnancy in the setting of women with a creatinine level of less than 1.4 mg/dL who are treated with prednisone and/or azathioprine.

An elevated prepregnancy creatinine level (i.e., >1.4 mg/dL) is not only associated with a higher risk of renal decline but also with a decreased fetal survival rate. The fetal survival rate is approximately 74% in patients with a creatinine level of more than 1.4 mg/dL, while it increases to about 96% in patients with a creatinine level of less than 1.4 mg/dL.

Immunosuppressive drugs in pregnancy

Prednisone crosses the placenta with a maternal-to-cord ration of 1:10. Fetal complications from the use of prednisone include neonatal adrenal insufficiency and thymic hypoplasia. These are unlikely to occur if the dose is less than 15 mg/d. If acute rejection of the kidney occurs during pregnancy, there is generally no hesitation in the use of high-dose steroids.

Azathioprine is teratogenic in animals, but this has not been found in humans. Although azathioprine apparently crosses the placenta, the immature fetal liver cannot convert it to its active form, 6-mercaptopurine. Use of azathioprine is associated with SGA babies and dose-related myelosuppression in the fetus.

Cyclosporine has not been associated with an increase in congenital anomalies but has been associated with SGA babies. Preeclampsia is also an associated complication (up to 29%), presumably from thromboxane and endothelin production. Tacrolimus crosses the placenta and has been associated with hyperkalemia and renal insufficiency. Insufficient data are available on the use of mycophenolate mofetil and sirolimus.

MANAGEMENT OF PREGNANCY                  

Clearly, a multidisciplinary approach is necessary, with physicians, nurses, and nutritionists representing renal, obstetric, and pediatric standpoints. Prepregnancy counseling, prenatal monitoring, and skilled obstetric management are critical to a successful pregnancy. Prepregnancy counseling should help select appropriate scenarios to encourage pregnancy. Encourage patients who have had a transplant to wait a year after a living relative donor transplant and 2 years after a cadaveric renal transplant before attempting pregnancy. In addition, renal function should be stable, with a serum creatinine level of less than 2.0 mg/dL. Blood pressure should be controlled, and proteinuria should be closely monitored.

In addition, medications should be reviewed. Discontinue ACE inhibitors, and make every attempt to decrease prednisone to 15 mg/d or less, azathioprine to 2 mg/kg/d or less, and cyclosporine to 5 mg/kg/d or less.

Infections pose an additional risk to these immunocompromised patients. Prepregnancy workups should also include a check of immune status for hepatitis B virus, herpes simplex virus (HSV), cytomegalovirus (CMV), and Toxoplasma species. In addition, if rubella titers are low, administer the vaccine before transplant because these live virus vaccine is contraindicated after transplantation.

Prenatal monitoring should include daily blood pressure measurements, usually taken by the patient. Biweekly physician visits with laboratory work consist of CBC counts, electrolytes, BUN and creatinine levels, and (if indicated) a cyclosporin level. Perform monthly ultrasounds and urine cultures. Determine immunoglobulin M (IgM) levels to CMV and Toxoplasma species for seronegative women every trimester. In the last trimester, check levels of IgM for HSV. In addition, biweekly fetal surveillance with a biophysical profile is indicated in the third trimester.

Obstetric management

The most common cause of mortality and morbidity in patients with any renal disease is preterm labor. Magnesium can be cautiously used to avoid toxicity and respiratory depression. The literature reflects a debate about elective early delivery (34-36 wk) in patients with chronic renal insufficiency or those receiving dialysis, especially when fetal lung maturity is present. In patients who have had a transplant, however, delaying delivery until the onset of labor is generally thought to be the most prudent step, provided, of course, that the mother and fetus show no signs of distress.

 
     

 
         
     

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