Renal disease with pregnancy

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Renal Diseases in
pregnancy
By
Ahmed Elbohoty MD, MRCOG
Assistant Professor
of
Obstetrics and Gynecology
Ain Shams University
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Introduction
• UTI is a common cause of maternal morbidity & a
potential cause of perinatal morbidity & mortality
via preterm labour.
• Renal disease is an important predisposing factor
for preeclampsia & FGR.
• The combination of proteinuria & hypertension at
booking in 1st or early 2nd trimester suggests a pre-
existing renal disease & should prompt further
investigations, such as serum creatinine.
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Introduction
• The number of women with renal transplant
considering pregnancy is increasing & success rates
are high, but case selection is required.
• Acute renal failure in pregnancy is rare, but renal
impairment & oliguria commonly accompany
obstetric conditions, particularly haemorrhage
(abruptio placenta) & preeclampsia.
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Renal adaptation to pregnancy
• Renal plasma flow increases by 60–80% over non-pregnant
values by the middle of the second trimester
• Glomerular filtration rate (GFR)
– starts to increase at 6 weeks of gestation, and
– rises to 50% over non-pregnant values by the end of the first
trimester however,
– it decreases by about 15–20% during late pregnancy.
• Renal haemodynamic augmentation impacts on
– Creatinine fall from a mean of 62 micromol/L to 44 micromol/L
– Urea fall from a mean of 4.3 mmol/L to 3.2 mmol/L
– increased urinary protein excretion with the upper limit
for proteinuria is taken as 300 mg / 24 hours
• Dilatation of ureters & renal calyces which makes
UTI more common during the pregnancy3/24/20 elbohoty 4
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In renal disease
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• Creatinine values of 80 micromol/L or more during
pregnancy suggest renal dysfunction
• The assessment of renal function by creatinine
levels alone is prone to error in women with
advanced renal dysfunction (i.e. Cr > 125
micromol/L)
• Urinary creatinine excretion results from both glomerular
filtration and tubular secretion, but the proportion formed by
secretion increases with advancing renal dysfunction.
• Hence, 'GFR' can be overestimated by up to 50%. Renal
function in these circumstances is better assessed by
creatinine clearance.
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Urinary tract infection (UTI) - Incidence
• It is more common in pregnancy to develop upper
urinary tract infections.
• Incidence of asymptomatic bacteriuria in
pregnancy ranges from 4% – 7%, of these about
40% will develop symptomatic UTI.
• Cystitis complicates about 1% of pregnancies.
• Pyelonephritis develops in about 1% – 2% of
pregnant women.
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Risk factors
• Those with a history of previous UTI.
• Diabetics.
• Women receiving steroids or immunosuppression.
• Women with polycystic kidneys.
• Women with reflux nephropathy.
• Women with congenital anomalies of urinary tract,
such as duplex kidney or ureter.
• Women with neuropathic bladder, such as those
with spina bifida or multiple sclerosis.
• Women with urinary tract calculi.
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Screening
• A midstream urine (MSU) specimen performed as
part of routine antenatal screening may reveal
asymptomatic bacteriuria.
• Additional MUS are indicated in women at
increased risk (every 4 to 6 weeks) & those with
symptoms of UTI.
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Diagnosis
• A clinical diagnosis should always be confirmed by
with culture of MSU sample.
• Bacteriuria is considered significant if there are
>100,000 organisms in 1 ml or urine.
• Urine culture revealing non-specific or mixed
growth should be repeated on a fresh MSU.
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Symptoms
• Cystitis:
– urinary frequency
– Dysuria
– suprapubic pain.
– haematuria, proteinuria
• pyelonephritis :
– Fever & rigors
– loin &/or abdominal pain
– vomiting
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Management
• All bacteriuria in pregnancy should be treated to
prevent pyelonephritis & preterm delivery
• For asymptomatic bacteriuria: A 7-day course of
treatment with an antibiotic is recommended
according to C&S
• Regular urine culture should be obtained after
treatment to ensure eradication of organisms.
• About 15-30 % will have recurrent bacteriuria
during pregnancy & will require a second course of
antibiotics.
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Pyelonephritis
• It complicates approximately 2% of pregnancies,
mostly during the second and third trimesters.
• Symptoms include backache, fever, rigors,
costovertebral angle tenderness, symptoms of
acute cystitis, nausea and vomiting.
• Women may also present with threatened preterm
labour.
• Bacteraemia can develop in 15–20% of these
women, and a small proportion will go on to
develop septic shock.
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Management
• Choice of antibiotic depends on sensitivities of
causative organisms.
• But, in suspected pyelonephritis, treatment should
begin before the results of culture are available.
• Penicillins (amoxycillin) & cephalosporins are safe
& appropriate.
• Augmentin (co-amoxiclav) increases the risk of
necrotizing enterocolitis in the neonate in case of
preterm deliveries.
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Urinary tract infection (UTI) - Management
• Cefadroxil 500mg bd is effective against the
majority of urinary pathogens.
• Nitrofuratoin is better avoided in the 3rd trimester
as it may cause neonatal jaundice
• Trimethoprim should be avoided in 1st trimester
because of its antifolate action.
• For acute cystitis, a 7-day course of antibiotics is
recommended & antibiotics should be continued
for 14 days for pyelonephritis.
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Management of pyelonephritis
• Hospital admission should be considered
– Antibiotics should be given by IVI.
– Treatment should continue with oral antibiotics once the
woman has been apyrexial for 24 hours.
– Treatment should be at least 14 days
– IV fluids may also be required.
– Renal function should be checked.
• Women who do not respond to treatment within 48–72
hours should be offered imaging of the urinary tract by
ultrasound to exclude any abnormalities
(hydronephrosis, congenital anomalies, renal abcess &
renal calculi.)
• Women admitted with pyelonephritis should be
considered for antenatal thromboprophylaxis for the
duration of their illness3/24/20 elbohoty 17
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Oral antibiotics
– Amoxycillin 500 mg … tds
– Cefadroxil 500 mg … bd
– Cephalexin 250 mg … tds
– Nitrofurantoin 100 mg … tds
• Not preferred in 3rd
trimester; because of haemolytic anaemia
in newborn
– Trimethoprim 200 mg … bd
• Not 1st trimester; because of antifolate action.
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Intravenous antibiotics for pyelonephritis
– Cefuroxime 750 mg – 1.5 g … tds
– Amoxycillin 1 g … tds
– Gentamicin 5 – 7 mg/kg … daily as one dose &
then further doses as determined by serum
gentamicin concentrations.
• For resistant organisms, or women allergic to penicillins
& cephalosporins.
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Duration of treatment
– Asymptomatic bacteriuria :7days
– Acute cystitis : 7 days
– Pyelonephritis : at least 14 days
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Prophylaxis of UTI
– Cephalexin 250 mg … od
– Amoxycillin 250 mg … od
– Nitrofrontoin 50 mg….od
• Continuous prophylactic antibiotics are only
usually indicated for those with ≥ 2 confirmed
(with a positive culture) UTI or with prescence
of risk factors.
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Renal stones
• The incidence of renal stones in pregnant women is
the same as for the general population
• More common in the second and third trimesters of
pregnancy
• associated with an increased risk of urinary tract
infection
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Investigations
• Urinalysis and microscopy culture and sensitivity of
a midstream urine sample
• Full blood count and urea and electrolytes
• Blood cultures if pyrexial
• Renal tract ultrasound will identify approximately
50% of renal stones in pregnant women
• If the diagnosis is uncertain,
– a plain abdominal radiograph could be considered, or
– magnetic resonance urography.
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Treatment
• Conservative management is successful in 70% of women:
– hydration
– analgesia
• paracetamol and opiates
• avoid non-steroidal anti-inflammatory drugs, especially in the third
trimester (renal and premature closure of ductus arteriosus in the fetus)
• epidural anaesthesia may relieve ureteric spasm and facilitate passage of
the stone
– broad-spectrum antibiotics for urinary tract sepsis.
• Consider intervention:
– If there is evidence of urinary tract obstruction on imaging
– if symptoms do not settle or
– renal function deteriorates consider
• Percutaneous nephrostomy (external urinary drainage) under ultrasound guidance
by an experienced interventional radiologist.
• Screen for asymptomatic bacteriuria every 4–6 weeks for the remainder of the
pregnancy.
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Long-term management
• Cystoscopy for stone removal by ureteroscopy
• Insertion of a double J stent
– (stents may become encrusted in pregnancy and may
therefore need replacing during pregnancy)
• Lithotripsy is contraindicated because of concerns
over the potential effects to the fetus.
• Follow up should include screening for
asymptomatic bacteriuria every 4–6 weeks for the
remainder of the pregnancy.
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Renal Impairment – Aetiology
• In women of childbearing age, the most common
causes of renal impairment are:
– Reflux nephropathy
– Diabetes
– Systemic lupus erythematosus (SLE)
– Other forms of glumerulonephritis
– Adult polycystic kidney disease
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Effect of Pregnancy on Renal Impairment
• Women with mild impairment (creatinine < 125 µmol/l)
tolerate pregnancy well, & usually do not suffer deterioration
in renal function because of pregnancy.
• Possible exceptions include women with:
1. scleroderma
2. periarteritis nodosa
3. membranoproliferative glomerulonephritis
4. IgA nephropathy ?
• Those with severe impairment (creatinine > 250 µmol/l) are
at increased risk of permanent loss of function during &
after pregnancy.
– 90% will have a permanent decline in function & even end-stage
renal failure (35% within 1 year after pregnancy).3/24/20 elbohoty 28
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• Scleroderma
– maternal deaths have been reported in association with
rapidly progressive scleroderma, as well as severe pulmonary
complications, infections, hypertension and renal failure.
– There have also been reports of severe disease reactivation
after apparently straightforward pregnancies.
• Periarteritis nodosa
– Successful pregnancies with periarteritis nodosa are
uncommon, mainly as a result of the associated
hypertension.
– Many reported cases involve maternal demise
– These cases are rare, and management should always include
consultation with a periarteritis nodosa expert.
• IgA nephropathy and membranoproliferative
glomerulonephritis/focal glomerular sclerosis
– Some believe that coagulation changes of pregnancy
exacerbate the natural course of the disease. This view is not
universally accepted.3/24/20 elbohoty 29
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Effect of Pregnancy on Renal Impairment
Prospects Category
Mild Moderate Severe
Pre-pregnancy plasma
creatinine
≤125 125–250 >250
Pregnancy
complications
26% 47% 86%
Successful obstetric
outcome
96% 90% 51%
Long-term sequelae >3% 25% 53%
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Effect of Renal Impairment on Pregnancy
• Maternal
– Deterioration in renal function during pregnancy
– Escalation of proteinuria leading to nephrotic syndrome
– Hypertension with or without superimposed pre-eclampsia
– Deterioration of anaemia
– Acceleration of disease progression
– VTE and pulmonary oedema especially in nephrotic syndrome
• Fetal
– Preterm delivery (usually iatrogenic)
– Uteroplacental insufficiency, e.g. fetal growth restriction and fetal or neonatal loss
– Miscarriage
– Polyhydramnios
• Effects of associated medical condition and medicines
• Outcome depends on the level of pre-existing hypertension and degree of
renal impairment.
• Those with severe renal impairment (creatinine > 250 µmol/l) & hypertension
have a less than 50% chance of successful pregnancy, often developing severe
early-onset preeclampsia with marked FGR.3/24/20 elbohoty 31
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Pre-pregnancy M a n a g e m e n t
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• Appropriate counselling
• Women who are advised to delay pregnancy
require advice regarding reliable contraception
• the timing of a pregnancy will be made on an
individual basis.
–women receiving haemodialysis may be advised
to wait until after a renal transplant to
contemplate pregnancy
–The importance of achieving good glycaemic
control prior to conception should be discussed
with women with diabetes.
–good control of the woman’s blood pressure prior
to conception.
–SLE in actvity should be in remission
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• Women with a heritable renal disease should be
offered referral to a clinical geneticist where
appropriate.
• Baseline investigations should be guided by the
woman’s underlying problem
• If the disease type is uncertain investigations to
determine disease type may be undertaken, which may
include imaging or a renal biopsy
• Serum urea and creatinine with an estimated
glomerular filtration rate and review of any changes
over the preceding year to assess the degree of renal
impairment
• Protein creatinine or albumin creatinine ratio to
quantify proteinuria/ albuminuria
• Full blood count to assess for anaemia
• Medication review
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Drug Indication Advice Alternatives
Angiotensin-converting-
enzyme (ACE) inhibitors
and angiotensin II
receptor blockers (ARB)
Antihypertensive
Reduces proteinuria
Renoprotection
Stop preconception due
to an increased risk of
congenital
abnormalities
Alternative
antihypertensives include
labetalol, methyldopa or
nifedipine
Statins Lipid control Stop preconception
Prednisolone Immunosuppressant Safe to continue
Azathioprine Immunosuppressant Safe to continue
Hydroxychloroquine Immunosuppressant Safe to continue
Calcineurin inhibitors,
ciclosporin and
tacrolimus
Immunosuppressant Safe to continue
Mycophenolate mofetil
(MMF)
Immunosuppressant Risk of congenital
abnormalities. Avoid
pregnancy
Sirolimus ImmunosuppressantRisk of congenital
abnormalities. Avoid
pregnancy
Cytotoxic agents,
such as
cyclophosphamide
and chlorambucil
Teratogenic. Avoid
pregnancy while
taking and for3
months afterwards3/24/20 elbohoty 36
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Pregnancy M a n a g e m e n t
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• Multi-disciplinary care by clinicians with expertise in management of these high-
risk pregnancies.
– Obstetrician, nephrologist, dietician, specialized midwife.
– The frequency of antenatal visits and assessments of fetal wellbeing should be made on
an individual basis, taking into consideration the woman’s clinical condition and degree
of renal impairment.
• Assessment and plan from booking visit:
• Full blood count, serum creatinine and electrolytes, uric acid, liver function tests
• Hb < 95 g/L give erythropiotien
• Assessment of proteinuria as
– > 1 gm is an indication for thromboprophylaxis
– to differentaite between future deterioration or superimposed preeclampsia
• Screening for asymptomatic bacteriuria with a midstream urine sample for culture
at lest once per trimester
• Review of current medications
• Venous thromboembolism risk assessment
• Folic acid 400 micrograms once daily (5 mg for diabetic women)
• Aspirin 75 mg once daily from 12 weeks of gestation until the birth of the baby for
prophylaxis to reduce the risk of hypertensive disorders in pregnancy
• Proper control of hypertension below 140/90 mmHg.
• Early Dating of pregnancy by ultrasound scan, anomaly scan at 18-20 weeks and
Growth surveillance with serial biometry and Doppler measurements should be
offered from 26 weeks of gestation.
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Hospital admission is considered
during
• worsening hypertension
• increasing serum creatinine
• large increases in proteinuria..
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diagnosis of preeclampsia can be
supported by
• FGR
• thrombocytopenia
• abnormal liver function
• Exclusion of lupus flare:
– Skin affection
– Complement consumption
– Increase in dDNA
• The diagnosis of pre-eclampsia is complicated by the fact that half of
pregnant renal transplant recipients have prepregnancy hypertension.
• The development of new proteinuria after 20 weeks of gestation is
diagnostically useful in women who are known to have no proteinuria in
early pregnancy.
• Alternatively, an increase in blood pressure to more than 160/110 mmHg or
an increase in treatment to maintain blood pressure at less than 160/110
mmHg or a 100% increase in proteinuria (from a level in early pregnancy to
a protein/creatinine ratio of greater than 30 mg/mmol) should be
considered suggestive of superimposed pre- eclampsia.3/24/20 elbohoty 43
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Timing of delivery
• The decision to electively deliver a baby in women
with chronic renal disease is complex and will
involve multiple maternal/fetal factors, including
gestation, type of disease and severity of renal
functional impairment.
• The following can be used as general
guidelines/prompts for delivery.
• Uncontrollable hypertension
• Irreversible and progressive deterioration in renal function
beyond the 15–20% seen near term
• Symptoms/signs of severe pre-eclampsia/impending eclampsia
• Signs of placental dysfunction, such that the risks of in utero
demise are greater than the risks of prematurity
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Magnesium sulphate
• It can be used for both fetal and maternal indications in women
with renal transplants.
• Dose
– The loading dose: 4 g is given irrespective of renal function
– Maintenance infusion: levels are halved in those with significant renal
impairment and/or oliguria.
• Observation should be undertaken for clinical signs of toxicity
during the loading dose and then up to every 4 hours including:
– maternal blood pressure
– respiratory rate
– oxygen saturation
– patellar reflexes
– fetal heart rate at baseline
• Serum concentration of magnesium can be checked at 4–6 hours
and consensus advice is to maintain a concentration of less than
3.5 mmol/L.
• Clinical assessment of toxicity may not correlate with serum
concentration of magnesium3/24/20 elbohoty 45
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Postnatal
• Check renal function soon after delivery and again
at 6 weeks post-delivery
• Ensure a VTE risk assessment has been made
• A postnatal review should be organised with the
woman’s obstetrician and her renal physician.
• The decision regarding the timing of the reviews will
be made on an individual basis
• Evaluate proteinuria and renal function outside of
pregnancy for women with renal disease first
detected in pregnancy
• A plan for postnatal contraception should be agreed
with the woman in the antenatal period3/24/20 elbohoty 46
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• The prevalence of renal transplantation in the UK is
2–6 per 10 000 women of childbearing age, with
30–40 pregnancies in renal transplant recipients
annually.
• The risk of acute rejection in the first year is
estimated to be 10–15%
• The majority of women with renal transplants will
have a successful pregnancy outcome.
• Rates of adverse maternal and fetal outcomes,
including pre-eclampsia, fetal growth restriction
and preterm delivery, are higher.
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Renal Transplants
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When?
• Conception is not advised within the first year
following renal transplantation when doses of
immunosuppressants are higher and graft stability
is more difficult to assess.
• Prognosis:
– pre-pregnancy renal function is satisfactory (serum
creatinine <125 micromol/L)
– graft rejection
– the presence of coexisting hypertension and proteinuria.
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Other factors related to the original
renal disease
• renal disease aetiology and previous vascular
disease burden need consideration.
• diabetic nephropathy are likely to have neuropathy
and retinopathy, and diabetic control will impact
pregnancy risk if simultaneous pancreas
transplantation was not undertaken.
• The antibody profile in women with a history of
lupus may also impact on pregnancy risk.
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Preconceptional care
• Criteria for considering a pregnancy
– Good general health for at least 12- 24 months post transplantation
– Good stable allograft function (serum creatinine preferably below 125
micromol/L)
– No recent episodes of acute rejection and no ongoing rejection
– Normotensive or minimal antihypertensive requirement
– Normal allograft ultrasound (no graft pelvicalyceal dilation)
– Recommended immunosuppressants at maintenance doses
• Prednisolone < 15 mg per day
• Azathioprine < 2 mg per day
• Ciclosporin or tacrolimus
• Pre-pregnancy
– Medication review
– Check calcineurin inhibitor levels
– Offer preconceptual advice for co-morbidities, such as diabetes mellitus
– Genetic issues
• Consider the input of a clinical geneticist for women with heritable renal
disease
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Medications
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Medications shift
• Mycophenolate mofetil can be switched to
azathioprine, which is considered safe in pregnancy.
• A 3-month time period following drug switch
facilitates the recommended ‘wash-out’ period for
mycophenolate mofetil prior to pregnancy, allows
confirmation of graft stability and can be used for
prepregnancy folate administration (400 mcg/day).
• ACEi and angiotensin receptor antagonists must be
discontinued during pregnancy.
• Statins should be stopped prior to conception.
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Antenatal management• The general principles of pregnancy management and decisions regarding elective delivery are the same as for women with chronic renal disease.
• Offer the same counselling that would occur at pre-pregnancy, if this has not been done
• Baseline assessment of renal function and proteinuria
– Proteinuria needs to be interpreted in the context of prepregnancy values. Proteinuria can be expected to double in pregnancy. If the woman
was taking an ACEi or angiotensin receptor antagonist prior to pregnancy, a further doubling can be anticipated when these teratogenic drugs
are discontinued.
– The frequency of renal function monitoring during pregnancy should be determined by the stability of renal function and the emerging clinical
picture, including concern regarding possible pre-eclampsia. Renal function and pre-dose tacrolimus/ciclosporin levels are checked no less than
monthly during pregnancy.
• Blood pressure should be maintained at less than 140/90 mmHg.
• Measure calcineurin inhibitor levels (tacrolimus/ciclosporin)
– Outside of pregnancy, calcineurin inhibitors (tacrolimus and ciclosporin) are titrated to a trough concentration within a range that prevents graft
rejection. Metabolismof these drugs is increased in pregnancy and serumlevels will fall. Regular monitoring of pre-dose ciclosporin or
tacrolimus blood levels is required, with dosing in pregnancy targeted to maintain the lower therapeutic level
– Clinicians should be aware that both ciclosporin and tacrolimus are metabolised by cytochrome p450 and that drugs that inhibit cytochrome
isoenzymes, including erythromycin and clarithromycin, can lead to calcineurin inhibitor toxicity. Alternative medications should be used where
possible.
• Test for GDMfor Women on calcineurin inhibitors and/or steroids
• Microbiology screening
– Screening for asymptomatic bacteriuria with a midstreamurine sample for culture
– Testing for hepatitis B, C, herpes simplex virus (HSV), cytomegalovirus (CMV), toxoplasmosis and rubella serology
• Venous thromboembolismrisk assessment
– Proteinuria adds to the hypercoagulable state of pregnancy and risk of venous thromboembolismand VTE prophylaxis is considered when the
urinary protein:creatinine ratio is more than 300 mg/mmol or the albumin:creatinine ratio is greater than 180 mg/mmol.
• Management of anaemia
– In normal pregnancy, erythropoietin concentration increases 2–4 fold. Even in the absence of significant transplant dysfunction, this increase
may not occur.
– Clinicians should be aware of the increased requirement for erythropoietin in pregnancy and consider treatment with erythropoietin stimulating
agents during pregnancy in anaemic pregnant women.
• Fetal surveillance
– Fetal growth scans should be performed at 26–28 and 32–34 weeks of gestation because of the risk of growth restriction.
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Timing of delivery
• Women should be offered a multidisciplinary
assessment at 30–34 weeks of gestation to discuss
mode of delivery with obstetric and transplant
surgical teams.
• Women taking more than 7.5 mg prednisolone per
day for more than two weeks during pregnancy
require intravenous hydrocortisone (50–100 mg
every 6–8 hours) during labour and until they are
able to tolerate oral medication.
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Management during labour
• Mode:
– Vaginal birth should be the aim
– Caesarean section reserved for obstetric indications.
• Onset:
– Associated indications for induction are usualy present
– Induction agents, including prostaglandins and oxytocin, are
safe to use in renal transplant recipients.
• Maternal monitoring:
– It is important to monitor maternal fluid balance,
temperature and cardiovascular status during labour.
– Women taking long-term steroids for immunosuppression
should receive steroid cover for labour or caesarean section.
• Fetal monitoring:
– Continuous electronic fetal monitoring is recommended
given the increased risk of placental dysfunction.
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CS
• Indications for a caesarean delivery should be
discussed with a consultant obstetrician in
conjunction with the surgical transplant team.
• The risk of trauma to the renal graft is estimated to
be 1–2%.
• Avoidance of renal graft trauma:
– The renal graft can also be located with ultrasound
immediately prior to skin incision.
– The uterine incision will usually be a transverse lower
segment incision.
– Consideration should be given to a midline skin incision
to reduce the risk of trauma to the allograft.3/24/20 elbohoty 56
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Postpartum and contraception
• Prior to discharge from hospital, blood pressure should be
stable and lower than 140/90 mmHg.
• In the context of pre- eclampsia or kidney injury,
haematological and biochemical parameters should be
improving.
• Women who require ongoing antihypertensive treatment can
have their medication rationalised and the 3–4 times daily
dosing that may have been required in pregnancy can be
converted to once or twice daily medication.
• Monitor fluid balance
• Thromboprophylaxis for 6 weeks postnatally with low-
molecular weight heparin if there is heavy proteinuria
• Check suitability of medicines with lactation
• A follow-up appointment should be made with the renal
transplant team. The timing of this appointment should be
individualised according to the pregnancy course and the
stability of transplant function.3/24/20 elbohoty 57
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Breastfeeding and medication
Prednisolone Systemic effects in the infant unlikely
with doses up to 40 mg daily
Azathioprine British National Formulary recommends
that women avoid breastfeeding.
Consensus opinion is there is no
absolute contraindication to
breastfeeding
Ciclosporin and tacrolimus British National Formulary recommends
that women avoid breastfeeding.
Consensus opinion is there is no
absolute contraindication to
breastfeeding
Mycophenolate mofetil No data, avoid breastfeeding
Sirolimus and everolimus No data, avoid breastfeeding
Furosemide No reports of adverse effects
Angiotensin-converting enzyme (ACE)
inhibitors
Captopril and enalpril
She can breast feed
Angiotensin receptor blocking agents Not recommended with breastfeeding
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Contraception
– Progestogen-only methods
• No adverse effects on renal allograft
– Combined oral contraceptive pill
• If normotensive and no other risk factors
• Use a low-dose pill
– Intrauterine contraceptive device
– Barrier
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59
Kidney donors during pregnancy
• doubling of the risk of gestational hypertension
and/or pre- eclampsia in kidney donors.
• aspirin prophylaxis in pregnancy for women who
have donated a kidney.
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60

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Dialysis
• Women on haemodialysis are relatively infertile.
• The incidence of pregnancy is around 0.3/100
patient years.
• Almost half of the pregnancies reported occured
within 2 years of starting dialysis.
• Less than 5% of reported pregnancies were
conceived after 10 years or more of dialysis.
• Early diagnosis of pregnancy in this group of women
remains a challenge because they are frequently
amenorrhoeic.
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61
Complications
• Increased risk of first and second trimester
miscarriage
• Risk of preterm birth (average gestational age at
delivery is 32–33 weeks) and a low birthweight
infant approximately 90%
• Polyhydramnios 18–40%
• Maternal hypertension or pre-eclampsia 75%
• Perinatal death 50% (related to prematurity)
• Anaemia
• preterm rupture of membranes
• placenta abruption.
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62

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Pregnancy care
• Prepregnancy counselling
– Pregnancy is more common and more successful after renal transplantation. Therefore postponing a pregnancy
until after a renal transplant is recommended
• Antenatal care
– Good blood pressure control
– Increase dialysis frequency
• Pregnancies are more successful with an increase in the frequency and duration of dialysis to over 20 hours
a week
– Maintain serum urea below 15–20 mmol/L
– Avoid maternal hypotension during dialysis (hypotension can impair uteroplacental perfusion)
– Ensure minimal fluctuations in fluid balance and volume changes
– Avoid hypercalcaemia
– Aspirin 75 mg once daily from 12 weeks
– Dietitian input
– Treat anaemia
• Increased requirement for exogenous erythropoietin
• May require parenteral iron
– Maintain close fetal surveillance
• Serial ultrasound scan for growth, liquor volume and Doppler
• Cardiotocogram with dialysis
• Peritoneal dialysis
– Continual ambulatory peritoneal dialysis can safely be continued during pregnancy. Its usefulness is limited by the
increasing size of the gravid uterus, which may make it impossible to continue effective peritoneal dialysis in later
pregnancy.3/24/20 elbohoty 63
63
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Acute Renal Failure in Pregnancy
• Rare in pregnancy
• mild degrees of renal impairment are more common &
it is usually related to preeclampsia or blood loss.
• Is usually complicates the early postpartum period.
• An isolated rise in urea (without creatinine) is often
observed following antenatal corticosteroid
administration.
• A rare cause of renal failure, that is most commonly
encountered postpartum is haemolytic uraemic
syndrome (HUS).
– The hallmark of this is a microangiopathic haemolytic
anaemia (diagnosis with a blood film) associated with acute
renal failure & thrombocytopenia.
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65
Most common causes are:
– Placental abruption
– Preeclampsia & related syndrome (e.g. HELLP)
– Infections
– Drugs, particularly non-steroidal anti-inflammatory
drugs
– Obstruction due to ureteric damage or stones
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Presentation
• The cause
• Oliguria
• a rising serum urea & creatinine
• a metabolic acidosis
• hyperkalaemia.
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67
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68

35. 3/24/20
35
Causes of ARF in pregnancy
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69
Treatment of the cause
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70

36. 3/24/20
36
Management
• Provide multidisciplinary management in a high-dependency
setting, combining the expertise of an obstetrician, renal
physician and neonatologist (if early delivery is anticipated)
• High dependency care
– Observations and consideration for invasive monitoring
– Monitor fluid balance (urinary catheter)
– Monitor serum urea and electrolytes
• Stop nephrotoxic medications
• Treat the underlying cause
• Consideration for renal replacement therapy (dailysis) in
women with:
– hyperkalaemia unresponsive to medical treatment
– volume overload (pulmonary oedema)
– severe metabolic acidosis
– uraemia3/24/20 elbohoty 71
71
The clinical approach to a pregnant
woman with AKI involves:
• fluid status assessment and consideration of fluid
replacement
• medication review
• appropriate diagnostic work-up early involvement of a
nephrologist for patients who do not respond to initial
management.
• Drug doses may need to be adjusted for a decrease in
glomerular filtration rate below 30 ml/minute including
antibiotics, anticoagulants, insulin and opiates.
• The use of NSAIDs is contraindicated in AKI
• Renal replacement may be indicted in severe AKI that fails to
respond to management or in women with chronic kidney
disease for whom superimposed AKI is more significant.
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Indications for renal replacement in
pregnancy
• metabolic acidosis
• hyperkalaemia
• fluid overload refractory to medical treatment.
• In addition, urea is teratogenic and a serum urea
above 17 mmol/l despite medical management is a
pregnancy-specific indicator for renal replacement
therapy.
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73
Management of hyperkalemia
• If AKI leads to hyperkalaemia, calcium salts for
cardiac stabilisation can be safely given in
pregnancy.
• Insulin with glucose can also be used as a
temporising measure to increase the intracellular
potassium shift while definitive treatment of the
AKI is undertaken.
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74

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38
Preeclampsia & Renal Failure
• Oliguria is almost universal in preeclampsia
• It is exacerbated by Syntocinon® & CS.
• Alone, it does not indicate renal failure, but should
prompt measurement of serum urea & creatinine.
• Renal failure is more common in acute fatty liver,
HELLP syndrome & eclampsia (6%) than in
‘straightforward’ preeclampsia.
• HELLP syndrome is the most common cause (50%)
of acute renal failure in the context of preeclampsia.
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75
HELLP
• AKI in HELLP can be severe enough to necessitate
temporary renal replacement therapy, but most
patients will recover renal function unless there is
underlying chronic kidney disease.
• Although HELLP parameters may deteriorate for 48
hours postpartum, recovery of haematological and
biochemical abnormalities should be expected.
• Where laboratory abnormalities do not remit after
delivery, and if platelet consumption and AKI
predominate the clinical picture, a differential diagnosis
of
– thrombotic thrombocytopenia purpura (TTP) and/or
– haemolytic uraemic syndrome (HUS) should be considered.
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76

39. 3/24/20
39
management of HELLP
• It is supportive and mirrors that of pre-eclampsia.
• A double-blind randomised controlled trial showed
that the use of steroids did not alter hospital stay,
recovery of laboratory parameters or complication
rates.
• Although the renal pathology is that of a
thrombotic microangiopathy, there are no
prospective trial data to either support or refute the
use of plasmapheresis.
3/24/20 elbohoty 77
77
Acute fatty liver of pregnancy
• Acute fatty liver of pregnancy is a rare obstetric
emergency with 5 cases per 100 000 maternities in
the UK.
• The disorder has been linked to fetal homozygosity
for disorders of beta-fatty acid oxidation leading to
an excessive fatty acid load in the mother, who is an
obligate heterozygote for the same mutation.
• AKI is a common complication of acute fatty liver of
pregnancy, with 14% of patients in the UK
developing renal impairment and 3.5% requiring
renal replacement therapy.3/24/20 elbohoty 78
78

40. 3/24/20
40
• Histological examination of the kidney: tubular free
fatty acid deposition, which links with the
pathogenesis in the liver.
• The main differential diagnosis of acute fatty liver of
pregnancy is HELLP because low platelets and
deranged liver function are part of the clinical
picture of both conditions. However, low serum
glucose, raised serum ammonia and prodromal
vomiting are more suggestive of acute fatty liver of
pregnancy.
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79
Management
• early diagnosis
• supportive care and prompt delivery.
• In most women there is recovery of liver
function and resolution of AKI after delivery.
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80

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SLE
• Systemic lupus erythematosus is an autoimmune
disease that affects women of childbearing age.
• Between 20% and 49% of women have renal
involvement and therefore lupus nephritis has the
potential to present for the first time in pregnancy
with AKI, proteinuria and hypertension.
• Distinction from pre-eclampsia is difficult and
specialist advice may be required.
• Increased lupus activity is described in pregnancy
with a 16% incidence of renal disease activation in
pregnancy and 10% of women with known lupus
nephritis develop acute renal failure in pregnancy.
3/24/20 elbohoty 81
81
Care
• Women with lupus remain vulnerable to a
postpartum flare of systemic lupus erythematosus
and should therefore remain under close
monitoring after delivery.
• Prednisolone, hydroxychloroquine and tacrolimus
can be safely used to treat lupus nephritis in
pregnancy.
• Mycophenolate mofetil is, however, teratogenic and
should be substituted with azathioprine
prepregnancy.3/24/20 elbohoty 82
82

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42
Thrombotic microangiopathy: TTP and
HUS
• Pregnancy-associated thrombotic microangiopathy
is rare, occurring in 1 in 25 000 pregnancies.
• Thrombi in the microvasculature lead to a
consumptive thrombocytopenia, mechanical
haemolysis and end-organ damage.
• Thrombotic microangiopathy has traditionally been
divided into two different clinical phenotypes:
– TTP
– HUS
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83
TTP HUS
Presentation primarily neurological
symptoms
predominant renal
dysfunction
Testing abnormalities in
ADAMTS13
complement pathway
dysregulation
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84

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43
Obstructive nephropathy
• It is rare in pregnancy.
• women with a single functioning kidney, including
women with a renal transplant, are more
susceptible to AKI when obstruction occurs.
3/24/20 elbohoty 85
85
Causes
– Autonomic neuropathy affecting bladder emptying
needs to be considered in women with diabetes with
microvascular complications and in multiple sclerosis,
and intermittent self-catheterisation may be required.
– Obstruction can also complicate urosepsis, for example,
as a result of abscess formation or pyonephrosis.
– A retroflexed uterus can lead to acute urinary retention
in the first trimester.
– Postpartum urinary retention occurs in up to 15% of
patients and has physiological, neurological and
mechanical causes.
– In the catheterised woman, excluding a blockage of the
catheter is the first diagnostic step in AKI.
– Renal stones are rare in pregnancy despite an increased
excretion of lithogenic substances by the kidney.3/24/20 elbohoty 86
86

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Presentation & diagnosis
• renal colic or infective symptoms
• Diagnosis is difficult in pregnancy because the
pelvicalyceal system and ureter dilate from as early
as 6–10 weeks of gestation
• Pathological obstruction is suggested on ultrasound:
– the ureter is dilated distal to the pelvic brim
– the obstruction does not decompress by positioning the
woman on all fours
– ureteric jets are absent even in the contralateral
position.
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87
Management
• Most patients will respond to expectant
management with
• Analgesia
• hydration and
• treatment of any underlying infection.
• If intervention is required:
– uteroscopic stone removal should be considered first-
line.
• AKI and infection are indications for intervention in
pregnancy with either percutaneous nephrostomy
or delivery if near term.
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88

45. 3/24/20
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SBA
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89
• You are asked to review a 32-year-old woman in the antenatal clinic who is
currently 13 weeks into her fourth pregnancy. She had an uncomplicated vaginal
delivery at term 7 years ago followed by two first-trimester miscarriages. She was
diagnosed with IgA nephropathy and needed a renal transplant (allograft) 2 years
ago. There is no other medical and no surgical history of note. She is not a smoker.
Currently, she is on prednisolone, azathioprine and tacrolimus. Her BMI is 26, her
blood pressure is 130/84 mmHg and she is not on any antihypertensive treatment.
Her recent blood test results are:
• haemoglobin: 10.2 g/dl
• serum albumin: 32 g/dl
• serum creatinine level: 110 micromol/l
• eGFR: 53
• urine protein:creatinine ratio: 15
• Her CMV titres were negative 4 months ago.
• Which of the following statement is most appropriate in her case regarding
pregnancy outcome and management?
• The chance of successful obstetric outcome is 97%
The chance of graft rejection is 20%
She will need serum azathioprine and tacrolimus levels every 2–4 weeks
Prophylactic anticoagulants should be started immediately
Prophylactic antibiotics are required to cover labour and any surgical procedure,
including episiotomy
•
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90

46. 3/24/20
46
• The correct answer is that the chance of successful
obstetric outcome is 97%. This is reduced to 75% if the
serum creatinine level is greater than 125 micromol/l.
Pregnancy appears to have a minimal adverse effect on
the long-term graft prognosis, provided that pre-
pregnancy renal function is satisfactory (serum
creatinine <125 micromol/l), and there is no graft
rejection. Prophylactic anticoagulation is not required
unless the women develops significant proteinuria or
has additional risk factors. Tacrolimus levels should be
checked every 2–4 weeks, but azathioprine levels are
not required. Prophylactic antibiotics are not required
on the basis of renal transplant alone.
3/24/20 elbohoty 91
91
• You are asked to review 21-year-old woman in maternity assessment unit who is currently at 26
weeks of gestation. She had been feeling unwell for the last 24 hours and presented with fever
with rigor, right loin pain, urinary frequency and vomiting. There is no history of abdominal
tightenings or vaginal loss and she reports normal fetal movements.
• On examination:
• pulse rate: 106 bpm
• blood pressure: 110/70 mmHg
• respiratory rate: 16 breaths per minute
• temperature: 38.2ºC
• moderate right renal angle tenderness
• well-grown baby with normal fetal heart rate on auscultation with hand-held Doppler.
• Urinalysis reveals 2+ proteinuria, 2+ red cells, 3+ leucocytes and nitrite positive.
• You have made a diagnosis of pyelonephritis.
• Which of the following statement is correct regarding pyelonephritis in pregnancy?
A. Women who do not respond to intravenous antibiotics within 24 hours should be offered
imaging of the urinary tract by ultrasound to exclude any abnormalities
B. Regular screening for asymptomatic bacteriuria should be offered to these women for the
remainder of their pregnancy because the recurrence rate of pyelonephritis is up to 40%
C. More common in pregnancy due to physiological dilation of the lower renal tract
D. Management in pregnancy consists of hospital admission, with hydration and treatment with
broad-spectrum intravenous antibiotics
E. Complicates 5–10% of pregnancies
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92

47. 3/24/20
47
• The correct answer is management in pregnancy consists of hospital
admission in most cases, with hydration and treatment with broad-
spectrum intravenous antibiotics. The antibiotics should be reviewed with
the urine culture results and adjusted according to the woman’s response
to treatment. Treatment should continue with oral antibiotics once the
woman has been apyrexial for 24 hours. Treatment courses of between 10
and 21 days have been recommended. Courses of 7 days or less are
associated with an increased incidence of relapse.
• The other possible answers are incorrect because:
• complicates 1–2% of pregnancies
• more common in pregnancy due to physiological dilation of the upper renal
tract (ureteral smooth muscle relaxation induced by progesterone or
compression of the ureters by the enlarging uterus)
• regular screening for asymptomatic bacteriuria should be offered to these
women for the remainder of their pregnancy because the recurrence rate of
pyelonephritis is up to 20%
• women who do not respond to intravenous antibiotics within 48–72 hours
should be offered imaging of the urinary tract by ultrasound to exclude
hydronephrosis, congenital abnormalities and renal calculi.
3/24/20 elbohoty 93
93
• You are asked to review the renal scan for Mrs Smith who is
currently at 35 weeks of gestation and has presented with right
loin pain, which started 1 week ago. She is haemodynamically
stable, apyrexial with minimal right renal angle tenderness.
Urinalysis is negative. Her renal function is normal, with serum
urea at 3.4 mmol/l and serum creatinine at 40 micromol/l. There is
mild hydronephrosis of right kidney, probably secondary to gravid
uterus, but it is an otherwise normal-looking kidney on renal scan.
• Which of the following statement is correct regarding physiological
renal adaptation to pregnancy?
• The 'physiological hydronephrosis' of pregnancy can be dismissed
as normal up to a pelvicalceal diameter of approximately 3 cm
Renal plasma flow increases up to 50% by the second trimester of
pregnancy
Creatinine values of 80 micromol/l or more during pregnancy
suggest renal dysfunction and should prompt further evaluation
Creatinine clearance rises by approximately 10%
Approximately 55% of pregnant women develop some oedema –
especially towards term – owing to physiological sodium and water
retention
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94

48. 3/24/20
48
• The correct answer is creatinine values of 80 micromol/l or more
during pregnancy suggest renal dysfunction and should prompt
further evaluation.
• The other possible answers are incorrect because:
• approximately 80% of pregnant women develop some oedema –
especially towards term – owing to physiological sodium and water
retention
• glomerular filtration rate starts to increase at 6 weeks of gestation,
and rises to 50% higher than non-pregnant values by the end of the
first trimester. Creatinine clearance rises by approximately 50%.
This results in fall in the serum urea and creatinine levels
• renal plasma flow rises very early in pregnancy and can increase by
60–80% by the second trimester of pregnancy.
• the 'physiological hydronephrosis' of pregnancy can be dismissed as
normal up to a pelvi-calceal diameter of approximately 2 cm.
3/24/20 elbohoty 95
95
• Mrs Smith is referred by her GP to the antenatal clinic for her
booking visit as she had a caesarean section in the past. She is
otherwise fit and healthy with no significant past medical history.
She is currently 11 weeks pregnant by her dating scan. She reports
no problems with her pregnancy so far. You were looking through
her booking bloods and MSU results done by her midwife 5days
ago. The MSU showed growth of E. coli > 105 colony forming units
per millilitre. She denies any urinary symptoms.
• You have made a diagnosis of asymptomatic bacteriuria.
• Which of the following statement is correct regarding
asymptomatic bacteriuria in pregnancy?
A. All pregnant women should be offered screening for
asymptomatic bacteriuria with urine dipstick tests in early
pregnancy as if untreated can lead to serious infection
B. Complicates 15–20% of pregnancies
C. Following successful treatment, 30% of women will have a
relapse of bacteriuria
D. If untreated, 5% of women will develop acute pyelonephritis
E. There is no association with preterm rupture of membranes
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96

49. 3/24/20
49
• The correct answer is following successful treatment, about
30% of women will have a relapse of bacteriauria.
• Note that:
• You should screen for asymptomatic bacteriuria early in
pregnancy with urine culture, not dipstick. In a prospective
international study, the dipstick tests missed 46% of all
pregnant women with asymptomatic bacteriuria.
• The incidence varies between 2% and 10% in non-pregnant
and pregnant women.
• Correct answer: Following successful treatment, monthly
screening of MSU is necessary, as about 30% of women will
have recurrent bacteriuria during their pregnancy requiring
second course of antibiotics.
• If untreated in pregnancy, 40% will develop symptomatic UTI
and 30% acute pyelonephritis.
• Increases the risk of preterm rupture of membranes, preterm
labour and low birth weight infants, if untreated. This is
thought to be as a result of either direct contamination of the
uterus or the action of systemic inflammatory mediators.3/24/20 elbohoty 97
97
• You are asked to review a 36-year-old woman in a joint obstetric–renal clinic who is
currently 16 weeks pregnant into her second pregnancy. She had an uncomplicated
caesarean section at term for breech presentation 13 years ago.
• She was diagnosed with reflux nephropathy and has been on haemodialysis for last 2
years. There is no other medical and surgical history of note. She is not a smoker. Currently
she is on calcium and vitamin D supplements, erythropoietin injection and pregnancy
vitamins.
• Her BMI at her booking visit is 20. Her BP is 120/78 mm Hg and she is not on any
antihypertensives.
• A recent blood test showed:
• haemoglobin: 102 gm/l
• serum potassium level: 4.8 mmol/l
• serum creatinine leve: 210 micromol/l
• serum urea level: 10 mmol/l
• eGFR: 10 ml/min/1.73m2
• normal bone profile
• normal plasma bicarbonate levels
• urine protein creatinine ratio: 95
• Which of the following statement is most appropriate in her case regarding pregnancy
outcome and management?
• Chance of successful pregnancy outcome is 30% with both haemodialysis and CAPD
(continuous ambulatory peritoneal dialysis)
Dialysis is usually associated with oligohydramnios
Duration of haemodialysis must be increased to more than 20 hours/week for improved
outcome
Maintain serum urea at 25–30mmol/L
Pregnancy rate is approximately 1 in 400 women per year3/24/20 elbohoty 98
98

50. 3/24/20
50
• The correct answer is duration of haemodialysis must be increased to more than
20 hours/week for improved outcome.
• Note that:
• Chance of successful pregnancy outcome is 50% with both haemodialysis and
CAPD. Poor prognostic features includes age >35 years, more than 5 years on
dialysis, delayed diagnosis of pregnancy leading to late increase in dialysis times.
• Dialysis is associated with polyhydramnios related to uraemia.
• Correct answer: Duration and/or frequency of haemodialysis must be increased to
more than 20 hours/week and almost to daily sessions. The disadvantages of
almost daily haemodialysis may include hypocalcaemia, alkalosis and hypokalemia.
Conversely, an increased dialysis frequency will allow for a more liberal diet and
protein intake, improving the nutritional status. Pregnancy outcomes are improved
when the sessions are prolonged to 4 hours occurs 6 times a week, the fluid
removal is limited to 400 ml per session, and the predialysis serum creatinine is
maintained at 4.5 mg/dL (397.8 micromol/l) or serum urea less than 15-20
mmol/L.
• The aim is to maintain serum urea at less than 15-20mmol/L
• Pregnancy rate is approximately 1 in 200 women per year.
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99