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)
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.
