IN THE NAME OF GOD

Kidney Replacement therapy & pregnancy

Dr sahar vahdat

Assistant professor of Nephrology

IUMS

1

Intruduction

Pregnancy is uncommon in women with end-stage renal disease (ESRD)

as Fertility rates are low in women on dialysis

Advancements in the delivery of dialysis and obstetric care have led to

improved live birth rates in women on dialysis, so pregnancy for young

women with ESRD is now more feasible and safer

However, these pregnancies remain high-risk for both maternal and

fetal complications, necessitating experienced multidisciplinary care

While transplantation remains the best option for many women

with ESRD desiring pregnancy, pregnancy on dialysis is now an

option for women who are unlikely to get a kidney transplant during their reproductive years

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Pregnancy Incidence

A recent meta-analysis noted a large increase in number

of reported cases of pregnancy in women on

hemodialysis (from 2000 to 2014)

This increase may reflect more intensified hemodialysis

regimens (use of high flux membranes, nocturnal therapy),

increased use of erythropoietin or a change in counseling practices

Pregnancy rates in women on peritoneal dialysis (PD) are lower than on hemodialysis:

A hypothesis is that hypertonic dextrose solutions and the fluid filled peritoneum interfere with ovum transit to the uterus

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Pregnancy Outcomes

More recent data from centers using intensified hemodialysis regimens during pregnancy report live birth rates greater than 80%

The analysis concluded that longer weekly dialysis times were

associated with lower rates of preterm delivery and small for

gestational age offspring

Women who initiate dialysis during pregnancy have improved

outcomes compared with those who conceive on dialysis. It is

hypothesized that the presence of residual renal function in the former group is protective

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Cont..

Offspring of mothers with ESRD have higher rates of prematurity, growth restriction, polyhydramnios, and stillbirth

There are several complications that are unique to PD including:exit site infections, catheter malposition and drainage difficulties, polyhydramnios,

and peritonitis

Catastrophic complications such as placental abruption and uterine trauma from the

PD catheter have been reported

Preterm deliveries, premature rupture of membranes, and stillbirth have been reported in association with acute peritonitis

Early reports demonstrated high rates of maternal morbidity, including severe

uncontrolled hypertension, preeclampsia, hemolysis, elevated liver enzymes

and low platelets syndrome as well as the need for frequent blood transfusions

5

Management of pregnant women on hemodialysis

Medication management

Discontinue teratogenic medications (ACE inhibitors, ARBs,

statin)

Double dose of water soluble vitamins

Add folic acid 5 mg/day

Consider low-dose aspirin for preeclampsia prevention

6

Management of pregnant women on hemodialysis

Dialysis Prescription Increase dialysis time: if no residual renal function, >36 h. If residual

renal function, time tailored to individual metabolic parameters with goal pre-HD BUN <50 mg/dL

Increase dialysate potassium concentration to 3 mEq/L

Increase dialysate bath calcium concentration to 3 mEq/L (1.5

mmol/L)

Sodium phosphate to dialysate or oral supplementation to

maintain serum phosphorus levels if necessary

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Management of pregnant women on hemodialysis

Blood pressure and volume

Target BP <140/90 mm Hg post-dialysis

Frequent clinical volume assessments to avoid intradialytic

hypotension and manage ultrafiltration volume

Dry weight increases throughout pregnancy by up to 0.5

kg/week during the second and third trimesters. Frequent

clinical assessments of volume status are the best way to

determine ultrafiltration targets

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Management of pregnant women on hemodialysis

Anemia

Intravenous iron to maintain optimal iron stores

Erythropoietin-stimulating agent to target hemoglobin 10–

11 g/dL

ESAs do not cross the placenta and are considered safe

in pregnancy

Iron sucrose is the preferred form of intravenous iron

during pregnancy

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Management of pregnant women on hemodialysis

Diet

Daily protein intake of 1.5–1.8 g/kg/day

Unrestricted diet including liberalized dietary phosphate

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Hypertensive disorders of pregnancy in women with

ESRD

Hypertension is a common medical comorbidity in women with ESRD

Hypertensive disorders of pregnancy, including gestational hypertension and

preeclampsia, are difficult to diagnose in this population because there are no

standard diagnostic criteria

Hypertension usually improves with intensified dialysis, and therefore

worsening hypertension after 20 weeks of gestation should raise the concern

for superimposed preeclampsia.

Slowing fetal growth, new fetal growth restriction and alterations in placental

Doppler blood flow are also more suggestive of placental causes of

hypertension

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Delivery

Delivery should take place in a center with neonatal intensive

care facilities, given higher rates of preterm delivery

There is no contraindication to a vaginal delivery in women

on hemodialysis

cesarean section should be reserved for the usual obstetric

indications

In pregnancies with no evidence of maternal or fetal

complications, patients are often induced at 37 or 38 weeks of

gestation

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Women with significant residual renal function should be able

to achieve adequate clearance with standard PD

prescriptions

Increasing dialysate volume and/or the number of exchanges

can be used to intensify PD dose

However as pregnancy progresses, the uterus limits larger

exchange volumes

Frequent exchanges via continuous ambulatory PD or

continuous cycling PD or addition of hemodialysis to

supplement PD clearance are often used

Management of the Pregnant Patient on Peritoneal dialysis

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Postpartum

no known contraindications to breastfeeding in women with ESRD on

hemodialysis

ACE inhibitors may be used post-partum for women who benefit

from renin-angiotensin-aldosterone system blockade for blood

pressure management. Captopril, enalapril, are the preferred ACE

inhibitors to use in the post-partum period as they are absent in

breast milk

ESAs and iron can be continued Emotional support is also essential

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pregnancy after renal transplantation

Renal transplantation has not only improved the survival of patients with end-

stage renal disease but also provided such patients with an opportunity to

restore their fertility Potential

Pregnancy is then common, occurring in 12% of women at childbearing age

Generally, the optimal timing of pregnancy in these individuals is at least 2

years after successful transplantation

pregnancy is permissible if graft function is optimal:

1. serum creatinine <1.5 mg/dL

2. protein excretion of <500 mg/24 hours

3. neither concurrent fetotoxic infections

4. nor the use of teratogenic or fetotoxic medications

5. stable immunosuppressive dosing at maintenance levels

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Antepartum evaluation

routine prenatal laboratory tests: complete blood count, blood type

indirect Coombs

rubella

syphilis

cervical cytology

screening for gestational diabetes

baseline and serial tests to monitor renal function are indicated

urine culture, serum creatinine and 24-hour urine collections for total

protein and creatinine clearance

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Cont..

viral infections are common with suppression of the immune

system and that present risks for both the mother and fetus

These include cytomegalovirus (CMV), herpes genitalis

(HSV), human papilloma (HPV), human immunodeficiency

virus (HIV), hepatitis B (HBV) and hepatitis C (HCV)

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Immunosuppressive drugs in

pgnarency

Glucocorticoids The most commonly used glucocorticoids are the short acting agents:

prednisone, prednisolone and methyl prednisolone

Adrenal insufficiency and thymic hypoplasia unlikely if the dose of prednisone has been decreased to 15 mg prednisone and prednisolone can

cross the placenta, but maternal‐ to cord‐blood ratios are approximately

10:1

Cases of cleft palate or mental retardation

increased frequency of premature rupture of membranes

aggravate hypertension serious maternal infection : Doses of prednisone greater than 20 mg/day

Treatment of rejection with steroids, if necessary, is not contraindicated, however, during pregnancy

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Azathioprine

In high doses (6 mg/kg), azathioprine is teratogenic in animals. In

human studies low birth weights, prematurity, jaundice, respiratory

distress syndrome and aspiration have been reported in kidney

transplant recipients Azathioprine has been associated with a dose‐related

myelosuppression in the fetus, but leukopenia is not usually a

problem in the neonate if the maternal WBC is maintained at values higher than 7500/mm

Azathioprine is used during pregnancy in many transplant recipients

64–93% of azathioprine administered to mothers appears in fetal blood as inactive metabolites

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Cyclosporin

Human data showed that adminstration of cyclosporin was

associated with low birth weights and a higher incidence of maternal

diabetes, hypertension and renal allograft dysfunction

Cyclosporin metabolism appears to be increased during pregnancy

and higher doses may be required to maintain plasma levels in the

therapeutic range Some of the pregnancies were complicated by pre‐eclampsia

Cyclosporine increases production of thromboxane and endothelin

Because of this, some physicians have suggested that the dose be limited to 2–4 mg/kg per day

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Tacrolimus

There is a paucity of data concerning the effect of tacrolimus

on pregnancy.

During pregnancy, the hepatic cytochrome P450 enzymes may

be inhibited, which can lead to increased serum level of

tacrolimus. The dose may therefore have to be significantly reduced to prevent toxicity (sometimes by as much as 60%)

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Sirolimus

Sirolimus (Rapamune), a macrolide antibiotic, has been

linked to small-for-gestational-age infants and delayed

bone ossificationcurrent recommendations are to avoid rapamycin for 6 wk

before pregnancy

22

Mycophenolate mofetil

There is concern based on animal studies that the risk of birth defect or abortion is increased in pregnant women exposed to MMF

Because precise data are limited at the moment do not recommend its use

all allograft recipients of childbearing potential who are taking

mycophenolate mofetil must receive contraceptive counseling and should

use two reliable forms of contraception simultaneously

These women should be made aware that this drug reduces blood levels of

the hormones in oral contraceptives and could theoretically reduce their

effectiveness

They should continue contraceptive use for 6 weeks after stopping mycophenolate mofetil and before attempting pregnancy

23

Criteria for transplant recipients contemplating pregnancy

At least 2year post‐transplantation

Stable renal function with creatinine < 1.5 mg/dl

No recent episodes of acute rejection

BP ≤140/90 mmHg on medications

Proteinuria <500 mg/day

Prednisone ≤15 mg/day

Azathioprine ≤2 mg/kg/day

Cyclosporin ≤4 mg/kg/day

Normal allograft ultrasound

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Management guidelines

Women who are not rubella immune should receive the rubella

vaccine before transplantation, because live virus vaccines are contraindicated post‐transplantation

Women are usually advised to wait at least 1 year after living related

donor transplantation and 2 years after cadaver transplantation

However, waiting 5 or more years may result in impaired renal function post‐partum that fails to recover, because of gradually

deteriorating renal function secondary to chronic rejection

25

Cont..

Contraceptive counselling should begin immediately after

transplantation, because ovulatory cycles may begin within 1–2

months of transplantation in women with well functioning grafts

Low dose oestrogen–progesterone oral contraceptive preparations

are advised

The risk of infection from the use of intrauterine devices is increased in

immunocompromised patients. The efficacy of IUDs may be reduced because of the anti‐inflammatory properties of immunosuppressive

agents

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Complications

Chronic hypertension and preeclampsia are the most common

maternal complications

Prematurity and low birth weight (<2500 g) is the greatest risk for the

infant

A number of rare and unusual emergencies have been reported that

include:

allograft rejection

overwhelming sepsis

eclampsia

stroke

rupture of the uterus renal vessel anastomosis

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Labour and delivery

Vaginal delivery is recommended in most transplant recipient women

Cesarean section should be performed only for standard obstetric

reasons

Care must be taken to avoid fluid overload and infection. At the time of

delivery, instrumentation should be minimized

In the perinatal period, the steroid dose should be augmented to cover the stress of labour and to prevent post‐partum rejection

Hydrocortisone, 100 mg every 6 h, should be given during labour and

delivery

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Breastfeeding

Breastfeeding is discouraged for patients taking any

immunosuppressive drugs

Cyclosporin measurement in maternal blood and breast milk

revealed a mean breast milk/maternal blood level ratio of 0.84

These levels can be toxic to a newborn

Similar recommendations exist for tacrolimus or other

immunosuppressive agents

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