PREGNANCY IN THE CHRONIC

DIALYSIS PATIENT
dr Frensi Ayu Primantari
 INCIDENCE AND DIAGNOSIS
• Infertility is common in dialysis patients with the
incidence of pregnancy in the end-stage kidney disease
(ESKD) being appoximately 2.2% per year in US.
• The luteal homone surge and the estradiol peak that
occurs mid to late menstruation with ovulation are
absent in uremia, possibly due to hyperprolactinemia
state found in ESKD
• While transplantation is the most effective way to
restore fertility in these patients, intensification of the
dialysis prescription by switching from intermittent
dialysis to nocturnal hemodialysis increased the
conception rate to 16,5% in a small series.
• The preponderace of anovulatory cycles with dialysis
makes amenorrhea difficult to interpret in woman with
suspected pregnancy
• While this should be investigated with β-human
chorionic gonadothropin (β-hCG) serum testing ,
caution should be exercised when interpreting hCG test
result in ESKD owing to high number of false positive
result
• The half life of circulating hCG is increased in this
patients, making the test unrelieble for calculation of
gestational age as well.
• Obstetric ultrasound is favored for estimation of
gestational age in pregnant women with ESKD, with the
mean gestational age at which the diagnosis of
pregnancy is made being 16,5 weeks
 DIALYSIS PRESCRIPTION IN THE
PREGNANT PATIENT
• Poor outcome for pregnacy in ESKD have been
attributed to uremia-induced disturbance in
hormonal homeostasis and the ensuing effects
on placentation and fetal growth.
• The increasing succes with fetal and maternal
outcomes with dialysis over the last decade
are largely due to intensification of the dialysis
prescription, with the best results coming
from long, nocturnal dialysis based regimens
• Nocturnal dialysis with a mean dialysis duration
of 36 hours preconception and 48 hours during
pregnancy in a cohort of seven pregnancies
resulted in a mean gestational age of 36,2 weeks
and mean birth weight of 2.417,5 ± 657 g.
• In a study by Hladunewich et al that compared
outcomes between a Canadian and American
cohort of pregnant dialysis women, the live birth
rates were 86,4% and 61,4% respectively (p =
0,03), and the mean gestational ages was 36,2
weeks and 27 weeks, respectively (p = 0,002).
• Notably, the Canadian cohort recieved a mean of 43
hours dialysis compared to 17 hours of dialysis
provided in the US.
• Intense dialysis regimens of five to seven times a week,
with each session lasting 8-10 hours, are associated
with improved outcomes leading to improved live birth
rates, decrease in prematurity, and improved live birth
rate, decrease in prematurity, and improved blood
pressure (BP) control.
• Intensive dialysis improves urea clearance, lowers
peripheral vascular resistance, and ameliorates
fluctuations in volume status
Commonly Used Drugs in Hemodialysis
and Their Use in Pregnancy
Drug Safety data Dosing and Pharmacology
Erythropoietin FDA category C Dosing similar to nonpregnant
state, typical pregnancy
requirement is double the
baseline dose, placental kinetics
unknown
Paricalcitol FDA category C Similar to nonpregnant state
Calcitriol FDA category B Similar to nonpregnant state
Calcium acetate FDA category C Similar to nonpregnant state
Savelamelar/lantha FDA category C No safety data/guidelines availble
num
Intravenous iron FDA category B Similar to nonpregnant state
Heparin FDA category C Similar to nonpregnant state,
does not cross the placental
barrier
• Daily dialysis offers the advantage of decreased
risk of hypotension owing to decreased fluid
removal per session and allow for high protein
intake to meet caloric needs of the fetus and
mother.
• It is also hypothesized that inceased solute
clearance with daily dialysis reduces placental
urea and thus reduces fetal osmotic diuresis and
resulting complications such as polyhidramnions.
• While maternal and fetal outcomes do not significantly
differ between hemodialysis and peritonela dialysis,
intensification of the dialysis prescription is easier on
hemodialysis. As with hemodialysis, a patient’s
treatment requirements will increase with peritoneal
dialysis especially during the later half of gestation
• A switch to continous cyclical peritoneal dialysis (CCPD)
with an increased frequency of small volume
exchanges, with suplemental manual exchanges, is
often required in late pregnancy to achieved adequate
clearance
• Using tidal peritoneal dialysis to successfully optimize
solute clearance in pregnancy with restricted
abdominal volumes has been reported.
• There are no changes in peritoneal dialysis efficacy in
pregnancy as measured by standard peritoneal
equilibration test (PET) of glucose and creatinine and
ultrafiltration efficacy
• Rarely, complications such as lacerations of the gravid
uterine veins from trauma to the peritoneal dialysis
catheter and preterm delivery from peritonitis during
pregnancy have been reported
• Dializers used during pregnancy range from standard high-
flux dializers to non-reuseable biocompatible dialyzers with
blood flows ranging from 200-400 ml/mnt
• There is a little data reported on vascular access for
maintanance hemodialysis in pregnancy in fluencing the
outcome
• In patients dialyzing with arteriovenous fistulae, the risk of
anuerysmal dilatation of fistual due to histologic changes in
the vessel wall associated with the hormonal changes in
pregnancy and altered pregnancy-related hemodynamics
must be factored into the routine examination of the
pregnant dialysis patient. Heparin does not cross the
placental barrier and can be used safely with hemodialysis
in pregnancy, without necessaitating a dose reduction
• The physiologic weight gain associated with
pregnancy, which is recomended to be 1-1,5 kg
within th 1st trimester and thereafter 0,3-0,5
kg/wk, should be factored into dry weight
assesment. With daily dialysis, fluids gains should
be minimal, and BP goal of < 140/90 mmHg
should be achievable with minimal
antihypertensives
• Persistent elevations in BP despite optimal fluid
removal should raise the suspicion of Pre-
eclampsia
• Target values of the main laboratory parameters suggested for
pregnant women on dialysis are similar to those advised in non-
pregnant dialysis patients. The pregnant patient is predisposed to
respiratory alkalosis as a result of progesterone-induced
hyperventilation
• Hence, a bicarbonate solution concentration as low as 25 mM is
preferred to standard higher concentrations to avoid superimposed
metabolic alkalosis
• With a standard 2,5 mEq/L calcium dialysate solution, the mother
will need 2 g of oral calcium per day to keep a positive calcium
balance and ensure the fetal calcium requirement of 25-30 g during
pregnancy
• The placenta secretes calcitriol which also aids in positive calcium
balance
• Intensive dialysis regiment during pregnancy can result in
hypophosphatemia
• Mot patients often do not require any phosphate binder, and at
times, addition of phosphorus to dialysate may be necessary
• In patients with hyperphosphatemia, calcium containing binders are
prefered due to their safety profile
• There is no experience with savelamer or lanthanum in pregnancy.
There is limitted data currently on the effect of pregnancy on
dialysis-associated metabolic bone disease profile
• Activated vitamin D analogs such as paricalcitol (pregnancy category
C) and calcitriol (prenancy category B) are dosed based on the
individual nephrologist’s discretion
 MANAGEMENT OF ANEMIA
• Anemia is common in pregnancy due to volume expansion
• Daily iron losses are also frequent in pregnancy
• In pregnant patients with ESKD, this physiologic anemia is exaggregated,
and most patients will require erythropoietin and iron supplementation
• Accentuated anemia and increased erythropoiesis-stimulating agents
(ESA) requirements are attributed to cytokine-induced erythropoietin
resistance and the effect of plasma volume expansion leading to
hemodilution
• ESA is not associated with fetal congenital anomalies at usual dose, and if
patients are on ESA when they become pregnant, the dose is typically
doubled for the length of pregnancy
• Intravenous iron supplementation can be given in pregnant dialysis
patients, given the expected physiologic need for an extra 700 to 1,150 mg
of elemental iron during pregnancy
• The US Food And Drug Administration has labelled intravenous iron is
category B for pregnancy
 NUTRITION
• Protein intake should be increased to meet
the metabolic needs of the mother and the
growing fetus. For this, a daily protein intake
of 1,8 g/kg is recomended
• Folate supplementation is higher than usual
doses is recomended for the pregnant mother
on dialysis and prevention of neural tube
defects
 PREGNANCY OUTCOMES
• FETAL OUTCOMES
• With intensification of dialysis dose, the rate of live births has escalated
from 23% in the 1970s to high of 87%
• In the Canadian cohort and in the nocturnal hemodialysis cohort reported
by Barua et al, the mean duration of the pregnancy was 36 weeks
compared to 32 weeks on previous reports
• Enhanced solute clearance with these regimens appears directly related to
fetal outcomes with significant negative corellation noted between blood
urea nitrogen (BUN) and birth weight/gestational age
• In a large registry perfomed in US, there was a non-significant trend
toward better survival and decreased prematurity in patients who
recieved > 20 hours of dialysis per week
• The ability to maintain maternal BP throughout pregnancy with minimal to
no antihypertensives also offers improved fetal perfusion, in regimens
such as described by Barus et al
• The ustralian and New Zeland Dialysis and
Transplantation (ANZDATA) registry compiled
all pegnancy data in dialysis patients between
1996 and 2008
• The registry noted superior live birth rates
among women who concieved prior to dialysis
initiation compared with those on dialysis at
the time of conception (91% vs 63%, p = 0,03)
• This study further noted that this significant
difference in live birth rate was secondary to
early pregnancy losses (<20 weeks of
gestation) in established dialysis patients
• However, beyond 20 weeks, these pregnancies
were similar with no significant difference in
gestational age or birth weight
 MATERNAL COMPLICATION
• Hypertension is the major clinical concern with
regard to the pregnant mother on dialysis
• This could manifest as gestational hypertension,
preeclampsia, or eclampsia.
• High placental urea leads to increased fetal solute
diuresis resulting in complication s such as
polyhidramnions
• Other frequently reported coplication s include
gestational DM, Premature Rupture of
Membrane, chorioamnionitis, placental
abruption, and hemorrage postpartum
 MANAGEMENT OF HYPERTENSION IN
PREGNANCY
• Hypertension is notable for earlier onset (<24 weeks) in
pregnant dialysis patients compared to pregnant
woman without ESKD. About 80% of all pregnant woen
on dialysis have a BP of 140/90 mmHg or above and
40% have severe hypertension as defined by systolic BP
> 200 mmHg or dialstolic BP > 110 mmHg
• Improved surveillance measures that include weekly
weight change assesments and daily BP measurements
at home are therefore recomended. Fluid status is first
determined when the mother is found to be
hypertensives
• Once euvolumia is establised, persistent elevations in BP are
managed with medications.
• Safe options include methyldopa (Class B), labetalol (Class C ;
selectives β-Blockers are associated with intrauterine growth
restriction), and calcium channel blockers (class C) and magnesium
laoding for seizure prophylaxis should be cautions with careful
monitoring of serum level
• Recently endothelial dysfunction and cardiovascular outcomes in
CKD and ESKD patients have been linked to an increase in soluble
fms-related tyrosine kinase 1, an inhibitor vascular endothelial
growth factor (VEGF). The antiangiogenic milieu created by a
relative VEGF deficiency with pre-eclampsia is redlected with
persistent elevations of sFlt1 in this population at baseline, making
it possible nontraditional cardiovascular risk marker in these
women, in addition to serving as a marker for superimposed
preeclampsia
 LABOR AND DELIVERY
• Pregnant woman on dialysis are considered high risk pregnancies and
need close coordination care between the nephrologist and obstetrician
• Biweekly antenatal monitoring to screen for fetal well being, biometry,
amniotic fluid index, cervical length, and umbilical artery pulsatility should
begin at 26 weeks of gestation and increased to weekly profiles near term.
Combinations of calcium channel blockers and magnesium should be
avoided due to profound maternal hypotension
• Caesarean sections are performed for obstetric indications and can be
performed in patients on peritoneal dialysis if indicated
• Newborn should be monitored in high risk neonatal care unit
• The baby’s BUN and creatinin will initially be elevated. This leads o solute
diuresis necessating careful monitoring of volume status and electrolytes
• A snapshot of key concept during and after the course of the pregnancy is
summarized in table 32.2
 Highlights of Hemodialysis
Management during Pregnancy
Prepregnancy During Pregnancy After Delivery
High-risk for fetal loss (<20 Best result with intense Readjust dry weight and
weeks) dialysis regimens of 5-7 antihypertensives
times/wk of 8-10 h/session
Stop ACEI and ARB before Expected weight gain 1-1,5 Watch for postpartum
or right after conception kg in first trimester and preeclampsia
0,3-0,5 kg/wk thereafter
Confirm pregnancy with Oral calcium and
obstetric ultrasound in phosphate supplements
addition to β-hCG results may be needed
Preconseption counseling ESA dose is tipically
about higher risks of early doubled for the length of
pregnancy losses, stillbirth, pregnancy
fetal prematurity, and
preeclampsia
 Highlights of Hemodialysis
Management during Pregnancy
Prepregnancy During Pregnancy After Delivery
Intravenous iron to
supplement in the extra
700-1,100 mg of elemental
iron needed
Protein intake of 1,8
g/kg/d and folate dose of
4-5 mg/d
Close surveillance for
preeclampsia
SUMMARY AND RECOMENDATION
• In summary, while the management of pregnancy in a
patient on dialysis remains complex and chalenging, huge
strides have been made over the last decade in terms of
gestational age, live birth rate and minimizing maternal
complications with intesification of the dialysis prescription
• Having an international registry for pregnancy outcomes in
dialysis patients will help pool experience with the complex
interface of pregnancy-related physiologic needs and
absence of the optimal renal adaptive response to this
state
• Close multispeciality monitoring and communication is the
key to succesful maternal and fetal outcomes, which will
hopefully be the standard of care with pregnancy in this
population