Lupus (2006) 15, 148155

www.lupus-journal.com

REVIEW

Lupus nephritis and renal disease in pregnancy

S Germain and C Nelson-Piercy*
Obstetric Medicine, Guys & St Thomas Hospitals, St Thomas Hospital, London, UK

Management of pregnant women with renal disease involves awareness of, and allowance for,
physiological changes including decreased serum creatinine and increased proteinuria. For women
with systemic lupus erythematosus (SLE), pregnancy increases likelihood of flare. These can occur
at any stage, and are more difficult to diagnose, as symptoms overlap those of normal pregnancy.
Renal involvement is no more common in pregnancy. Worsening proteinuria may be lupus flare but
differential includes pre-eclampsia. In women with chronic renal disease, pregnancy may accelerate
decline in renal function and worsen hypertension and proteinuria, with increased risk of maternal (eg,
pre-eclampsia) and fetal (eg, IUGR, IUD) complications, strongly correlating with degree of renal
impairment peri-conception. Pregnancy success rate varies from 20% to 95% depending on base-line
creatinine. Best outcome is obtained if disease was quiescent for 6 months pre-conception. Women
on dialysis or with renal transplants can achieve successful pregnancy but have higher maternal and
fetal complication rates. Acute on chronic renal failure can develop secondary to complications such
as HELLP and AFLP. Management needs to be by a multidisciplinary team involving physicians and
obstetricians, ideally beginning with pre-pregnancy counselling. Treatment of flares includes
corticosteroids, hydroxychloroquine, azothioprine, NSAIDs and MMF. Blood pressure is controlled
with methyldopa, nifedipine or hydralazine. Lupus (2006) 15, 148155.
Key words: nephritis; pregnancy; renal

Physiological changes in pregnancy

During pregnancy the urinary collecting system
markedly dilates, the result of a combination of
progesterone-induced ureteral smooth-muscle relaxation, and compression of the ureters by the enlarging
uterus or iliac vessels. A pelvicalceal diameter of
up to 2 cm is usually allowed as physiological
hydronephrosis of pregnancy. There is also an
increased risk of pathological hydronephrosis and of
pyelonephritis. For anatomical reasons this is more
frequently on the right than the left.
Renal plasma flow rises from early in pregnancy,
and by the second trimester has increased by 6080%.
It then falls throughout the third trimester, but at term
is still 50% greater than pre-pregnancy values.
The glomerular filtration rate (GFR) increases
by 55%, creatinine clearance rises by about 50% to
120160 mL/min, and there is a resultant fall in

*Correspondence: Catherine Nelson-Piercy, Consultant Obstetric

Physician, Guys & St Thomas Hospitals, 10th Floor, North Wing,
St Thomas Hospital, Lambeth Palace Road, London SE1 7EH, UK.
2006 Edward Arnold (Publishers) Ltd

serum urea (24.5 mmol/L) and creatinine levels

(2575 mol/L). Normal ranges differ in pregnancy
both from non-pregnant and between trimesters. For
example, with creatinine; first trimester 5268 mol/L,
second trimester 4464 mol/L, and third trimester
5573 mol/L.
Proteinuria is increased, due to increased excretion,
and levels of up to 300 mg/24 hours are considered
within the normal range in pregnancy. There is no
increase in glomerular capillary pressure, and no longterm adverse effects on glomerular morphology.
During pregnancy, there is physiological sodium
and water retention, with decreased ability to excrete a
sodium and water load, especially near term. This
means up to 80% of pregnant women develop some
oedema, especially in the late third trimester, so it is
not usually a pathological sign.
There are a number of renal vasodilators produced
in pregnancy. These include prostaglandins, endothelium derived relaxing factor (EDRF)/nitric oxide (NO)
and relaxin. EDRF/NO mediates both vasodilation and
hyperfiltration. Relaxin is produced by the corpus
luteum, stimulated by hCG, and increases in the luteal
phase and more markedly after conception. When
given exogenously to non-pregnant rats there is an
10.1191/0961203306lu2281rr

Renal lupus in pregnancy

S Germain and C Nelson-Piercy

149

increase in GFR, and in humans in the luteal phase

GFR also increases by 15%.
Hormonal changes include increased levels of
erythropoietin, renin and vitamin D, with reduced
PTH. Uric acid falls in early pregnancy, but then
increases with increasing gestation, and bicarbonate
levels are reduced to 1822 mmol/L.

Chronic renal failure in pregnancy

Effect of pregnancy on renal disease
Pregnancy may accelerate the decline in renal
function of 2% to 75% of women with chronic renal
disease, depending on the baseline creatinine. They
are also more prone to escalating hypertension and
worsening proteinuria during their pregnancy, even if
there is no superimposed pre-eclampsia. Up to
doubling of the quantity of proteinuria is generally
allowed as a physiological response to pregnancy,
but greater than this needs investigation for possible
pre-eclampsia or a lupus flare. Initially in all but
those with very severe renal impairment, the usual
increase in GFR occurs, leading to a fall in the
serum creatinine level early in pregnancy. However,
in those with moderate and severe renal impairment,
the serum creatinine level usually begins to rise
to and beyond pre-pregnancy levels during the
second trimester.
Effect of renal disease on pregnancy
Women with chronic renal disease have an increased
risk of both maternal and fetal complications during
pregnancy. These include miscarriage, intrauterine
growth retardation (IUGR), intrauterine death (IUD),
preterm delivery (and the associated morbidity and
mortality), and pre-eclampsia. The increased risk of
pre-eclampsia applies even to those women whose
renal function is good and BP normal on entering
pregnancy. Twenty-five percent of those with a baseline creatinine 125 mol/L develop maternal
complications, and this rises to 85% if creatinine
is 250 mol/L.

lastly, the underlying type of renal disease. In general,

women without hypertension or renal impairment
prior to conception have successful pregnancies, and
pregnancy does not adversely influence the progression of the renal disease.
Degree of renal impairment
The degree of renal impairment at conception strongly
correlates with the likelihood of renal deterioration,
maternal and fetal complications, and pregnancy
success rates. This is demonstrated in Tables 1 and 2.
Most of the studies comparing these various outcomes for the degree of renal dysfunction have based
the latter on serum creatinine levels. These may be
misleading if allowance is not made for the womans
size, and further studies using GFR instead would
be useful. The Cockcroft Galt equation to calculate
GFR from serum creatinine is not applicable in
pregnancy.
Women with more severe renal impairment are more
likely to have an accelerated decline and/or a permanent
worsening of renal function as a result of the pregnancy
(Table 1). If creatinine is 125 mol/L at conception
then in only 2% will renal function deteriorate during
pregnancy, with no significant progression to end-stage
renal failure or deterioration post-partum. At the other
end of the spectrum, if creatinine is 170 mol/L at
conception, then in 6575% renal function will worsen
during pregnancy, 5060% will have further deterioration post-partum and 3340% will develop end-stage
renal failure. Even in the middle ground, with creatinine
125170 mol/L, renal function will deteriorate further
during pregnancy in 40%.
Table 1

Effect of pregnancy on renal impairment

Degree of renal impairment

Mild

Moderate

Creatinine (mol/L)
Loss of function
Postpartum deterioration
End-stage renal failure

125
2%

125170
40%
20%
2%

Severe
170220
65%
50%
33%

220
75%
60%
40%

Source: Nelson-Piercy C. Renal disease. In Handbook of Obstetric

Medicine, third edition. Taylor Francis, 2006.

Table 2 Effect of degree of renal impairment on pregnancy

outcome

Factors affecting outcome

Degree of renal impairment

Mild

Moderate

Severe

At the time of conception, there are a number of

important factors that will influence the likelihood of a
successful pregnancy outcome and any adverse
effect of pregnancy on the underlying renal disease.
First, the presence and degree of renal impairment;
second, the presence and severity of hypertension;
third, the presence and degree of proteinuria; and

Creatinine (mol/L)
Maternal complications
eg, pre-eclampsia
IUGR
Preterm delivery
Pregnancy success

125
25%

125250
50%

250
85%

8595%

30%
55%
6090%

60%
70%
2030%

Source: Nelson-Piercy C. Renal disease. In Handbook of Obstetric

Medicine, third edition. Taylor Francis, 2006.
Lupus

Renal lupus in pregnancy

S Germain and C Nelson-Piercy

150

The severity of renal impairment also determines

the risk of maternal and fetal complications during
pregnancy. If creatinine is 125 mol/L there is a
8595% pregnancy success rate, although 25% will
develop maternal complications such as pre-eclampsia.
Whereas, with creatinine 250 mol/L, pregnancy
success rate is only 2030%, 85% develop maternal
complications, 60% of babies are growth restricted,
and 70% preterm.
Another important factor in determining development of fetal complications is maternal urea level. If
urea 10 mmol/L, polyhydramnios may develop, and
the accompanying risks of preterm rupture of the
membranes and cord prolapse. This is because the high
maternal urea level leads to an osmotic load on the
fetus, and resultant fetal polyuria. Once the maternal
urea level is 2025 mmol/L, there is also a risk of
fetal death.
Dialysis and pregnancy
Fertility is markedly reduced in women on haemodialysis or chronic ambulatory peritoneal dialysis
(CAPD), and the pregnancy rate is only about one in
200 women per year. The chance of a successful
pregnancy outcome is also reduced to about 30%. Poor
prognostic features for pregnancy in dialysis patients
include age 35 years, more than five years on
dialysis, and delayed diagnosis of pregnancy (leading
to late increase in dialysis times).
If a woman is able to become pregnant, then her
dialysis requirements will markedly increase. Both the
duration and frequency of dialysis usually need to be
increased, to a total of 20 hours per week, with
sessions on five to six days per week. Continued
adherence to fluid restriction is important to avoid
large fluid shifts during dialysis, as fluctuations in
blood pressure and fluid balance are already more
common in pregnancy. Dietary restrictions can usually
be lifted. The aim should be to maintain the predialysis urea at 1520 mmol/L, to avoid the fetal
complications discussed previously.
The procoagulable state of pregnancy may
also mean increased heparin doses to prevent
clotting of dialysis lines. Anaemia is exacerbated by
pregnancy, and transfusion requirements increase.
Erythropoietin and intravenous iron can be used
safely in pregnancy, and doses or frequency may also
need to be increased. Conversely, doses of vitamin D
and calcium may need to be reduced. Pregnant
women on dialysis have an increased risk of
hypertension and pre-eclampsia, miscarriage, intrauterine death, preterm labour, preterm rupture of
membranes, polyhydramnios related to uraemia, and
placental abruption. The increased heparinization
Lupus

requirements during haemodialysis also increase the

risk of bleeding. Women on CAPD are at risk of
peritonitis.
Renal transplants and pregnancy
Fertility usually returns to normal post-transplant, and
it is important to educate these women regarding the
need for contraception, as they may have been anovulatory and oligo/amenorrhoeic previously and not
required contraception. If women wish to get pregnant,
they should be advised to wait about one to two years
after transplantation, with no recent episodes of
rejection, to allow graft function to stabilize and
maintenance levels of immunosuppressive drugs to be
reached, to minimize any risk to the fetus. Successful
pregnancy outcome for those transplant recipients who
become pregnant and do not miscarry before 12 weeks
is now 95%.
Renal allografts adapt to pregnancy in the same way
as normal kidneys, with an initial increase in GFR and
dilatation of the collecting system, and then a fall in
GFR in the third trimester. As discussed for chronic
renal disease in general, any adverse effects of
pregnancy on the renal allograft will depend on the
baseline serum creatinine. Poor graft function at
conception, higher baseline serum creatinine, and the
presence of hypertension, increases the risk of deterioration in graft function. Pregnancy usually has no
adverse long-term effect on renal allograft function or
survival in women with baseline creatinine levels
100 mol/L. Conversely, renal graft survival is only
65% at three years, if women enter pregnancy with
serum creatinine 130 mol/L. More than 10% of
women are likely to develop new long-term problems
following pregnancy, but it is difficult to ascertain
whether this is actually as a direct result of pregnancy.
The risk of long-term problems is higher in women
developing pregnancy complications prior to 28
weeks gestation. About 10% of women will die within
one to seven years after pregnancy, and about 50%
within 15 years.
Pregnancy outcome is best in those without
hypertension, proteinuria, recent episodes of graft
rejection, and in those with normal or near-normal renal
function (serum creatinine 125 mol/L). For a baseline creatinine 125 mol/L the chance of a successful
pregnancy outcome beyond 12 weeks is 97%, but this
is reduced to 75% for creatinine 125 mol/L. Women
with diabetes, and those with poor graft function, have
a higher complication rate. The incidence of problems
overall is about 50%, including graft rejection (10%),
hypertension/pre-eclampsia (30%), IUGR (2040%),
preterm delivery (4560%), and infection (especially
urinary tract infection).

Renal lupus in pregnancy

S Germain and C Nelson-Piercy

151

Renal lupus and pregnancy

Flares during pregnancy
Pregnancy increases the likelihood of a lupus flare,
from about 40% to about 60%. These are not usually
more severe than in non-pregnant women, and recent
evidence does not suggest that flares are more likely
immediately postpartum. Lupus flares may occur at
any stage of pregnancy or the puerperium. It is not
possible to predict when, or if, an individual patient
will flare, although flare is more likely if disease has
been active within six months of conception. The type
of flare can to some extent be predicted by a womans
previous disease patterns.
Flares are not prevented with prophylactic
steroids or routine increases of dose, so such prophylactic therapy is not recommended either ante- or
postpartum.
One difficulty diagnosing a flare during pregnancy is
that many of the features also occur in normal pregnancy, such as oedema, palmar and facial erythema,
fatigue, anaemia, raised ESR, musculoskeletal pain and
hair loss. Another difficulty is that active lupus has overlapping features with other pregnancy complications.
Lupus nephritis
For a woman with SLE, renal involvement is no more
common in pregnancy, although lupus nephropathy
may manifest for the first time in pregnancy.
As already discussed for chronic renal disease,
pregnancy does not seem to jeopardize renal function
in the long term in general, but this will depend on
factors such as baseline creatinine. The presence of
anti-phospholipid antibodies (anticardiolipin antibodies or lupus anticoagulant, APLs) does have a potential
deleterious impact on renal outcome, as well as
increasing the risk of thrombosis and adverse obstetric
outcome. Women should be advised to delay pregnancy until at least six months after a lupus nephritis
flare, to reduce their risk of a further flare during
pregnancy.
Worsening proteinuria in pregnancy could herald a
lupus flare, but the differential diagnosis would also
include the physiological response to pregnancy, the
effect of discontinuing an ACEi during pregnancy, and
pre-eclampsia. Up to a doubling of baseline proteinuria may be expected in pregnancy but more than this
would be indicative of either worsening lupus
nephritis or pre-eclampsia. Distinguishing between
active renal lupus and pre-eclampsia is notoriously
difficult, and the two conditions may be superimposed.
Hypertension, proteinuria, thrombocytopenia and renal
impairment are all signs they have in common, so

diagnosis of lupus flare requires other features, such as

increasing anti-dsDNA titre, fall in complement levels
C3 and C4, red blood cells or cellular casts in the
urinary sediment, and other symptoms of flare such as
arthralgia and skin rash. Conversely, hyperuricaemia
and abnormal liver function tests are unusual in a lupus
flare, and point more towards pre-eclampsia. The only
definitive investigation to reliably differentiate
between the two is a renal biopsy, but this is rarely
undertaken in pregnancy. It may be indicated though
prior to fetal viability, since confirmation of active
lupus nephritis allows immunosuppressive treatment
of the SLE, and delaying of delivery. Beyond 2428
weeks gestation, when the fetus is viable, delivery
may be the most appropriate course if the mother or
her fetus is at risk. This will both cure pre-eclampsia
and allow administration of drugs such as cyclophosphamide for a renal flare.
Effect on pregnancy
Overall, SLE pregnancies have an increased risk of
spontaneous miscarriage, pre-eclampsia, IUGR, fetal
death, and preterm delivery. The degree of risk
depends on a number of factors including the presence
of lupus nephritis, hypertension, APLs, active disease
at the time of conception, and first presentation of SLE
during pregnancy. Pregnancy outcome is particularly
affected by renal disease, and even quiescent renal
lupus is associated with increased risk of fetal loss,
pre-eclampsia and IUGR, particularly if there is hypertension or proteinuria. Anti-phospholipid syndrome
(APS) is also associated with a worse prognosis.
Conversely, for women in remission, or without the
risk factors mentioned above, the risk of pregnancy
loss and pre-eclampsia is probably no higher than in
the general population. Another complication of
pregnancy in women with SLE or APS, although very
rare, is chorea.

Management of renal disease in pregnancy

Pre-pregnancy counselling
Management should begin with pre-pregnancy counselling. Assessment of pre-conceptual renal function,
proteinuria, blood pressure, anti-Ro/La antibodies and
APLs enables accurate counselling and provides a
baseline with which to compare trends in pregnancy. In
view of the increased risk of pre-eclampsia, treatment
with low-dose aspirin should be considered, especially
in those with hypertension and renal impairment or a
previous poor obstetric history, and folic acid should
be started. Timing of pregnancy should be discussed,
inparticular, stressing that outcome is improved if
Lupus

Renal lupus in pregnancy

S Germain and C Nelson-Piercy

152

conception occurs during disease remission and at

least six months after a flare. Realistic, evidence based,
estimates should be given for likely success and
chance of complications, and the possibilities of prematurity and handicap discussed. If renal impairment
is severe (baseline creatinine 250 mol/L), then
women should usually be advised against pregnancy,
because of the very high risks of maternal and fetal
complications and low chance of success, and appropriate contraception discussed.

Table 3

Use of drugs in pregnancy

Yes

No/caution

Cyclosporin
Tacrolimus
Azathioprine
Prednisolone
Penicillins
Gentamicin
Alpha-blockers
Calcium antagonists

MMF
Cyclophosphamide
Rapamycin
ACE inhibitors and A2RB (OK in first trimester)
Beta-blockers (OK in later pregnancy)
Diuretics
Statins

ACE: angiotensin converting enzyme; A2RB: angiotensin II receptor

blockers.

General management
Pregnancy care is best undertaken by a multidisciplinary team in combined clinics, involving both physicians and obstetricians with expertise in the care of
renal disease in pregnancy.
It is important to establish baseline values in early
pregnancy for Fbc, U and E, serum creatinine, uric
acid, liver function, anti -dsDNA and complement
titres and to quantify any proteinuria. The woman
should have regular assessment of renal function by
serum creatinine and urea, as well as creatinine
clearance and 24-hour protein excretion or protein
creatinine ratio. It may be useful to give the woman
urine testing strips so she can monitor the presence and
severity of any proteinuria or haematuria. The woman
should be assessed regularly for evidence of disease
activity, and other markers, such as dsDNA and
complement titres, repeated as indicated.
Anaemia is common and haematinics should be
prescribed. Maternal hypocalcaemia and hypercalcaemia are both potential problems, and calcium status
should be carefully monitored. Doses of calcium and
vitamin D may need to be altered in pregnancy.
The fetus should be monitored with regular
ultrasound scans for growth and liqor volume. Doppler
assessment of uterine artery blood flow at 2024
weeks is useful in predicting pre-eclampsia and IUGR,
and assesment of the umbilical flow is helpful in the
presence of IUGR.
As already discussed, the indications for renal
biopsy during pregnancy are mostly limited to situations where a delay before delivery is desirable (ie,
before 32 weeks gestation) and a diagnosis of a steroid
or chemotherapy-responsive lesion is suspected.
See Table 3 for a summary of the safety of the
various immunosuppressant, anti-hypertensive, and
other drugs in pregnancy. They are discussed in more
details in the following sections.
Management of lupus flares and medication
Hydroxychloroquine is often used to prevent flares.
It should not be stopped in early pregnancy, as this
Lupus

could precipitate a flare, and its long half-life means

that the fetus would continue to be exposed to the
drug for several weeks even after discontinuation.
Doses at the level used for malarial prophylaxis appear
to be safe for the fetus, but there have been concerns
that higher doses used for rheumatic disorders,
could result in fetal retinopathy. Evidence from a
randomized control trial of pregnancies in women
exposed to hydroxychloroquine though, have shown
the congenital abnormality rate is no higher than
the background population, and there were fewer
flares, less prednisolone used, and a decreased
SLEPDAI (SLE in Pregnancy Disease Activity Index).
Disease flares must be actively managed.
Corticosteroids are the drugs of choice, usually
increased oral prednisolone or pulsed intravenous
methyl predisolone. Pregnant women receiving
steroids are at increased risk of gestational diabetes
mellitus and of premature rupture of membranes. If
they are on a dose of 7.5 mg prednisolone for 2
weeks, then parenteral steroids will be required to
cover the stress of labour and delivery, regardless of
the mode of delivery.
Azathioprine can be added as a steroid sparing
agent. It is safe to use in pregnancy, with no adverse
fetal effects reported despite many years experience with its use. The fetus lacks the enzyme to
convert azathioprine to its active metabolites.
There are also only very low levels of the active
metabolites of azathioprine in breast milk, and some
authorities would argue that the benefits of breast
feeding outweigh any potential risk of neonatal
immunosuppression.
NSAIDs can be used as second line treatment, in the
first and second trimesters, but are usually stopped in
the third trimester by 3234 weeks, because they can
cause oligohydramnios (due to effects on the fetal
kidney), premature closure of the ductus arteriosus
(due to inhibition of prostaglandin synthetase), and
neonatal haemorrhage (due to inhibition of platelet
function).

Renal lupus in pregnancy

S Germain and C Nelson-Piercy

153

Like azathioprine, mycophenolate mofetil (MMF)

is an antiproliferative immunosuppressant. It is however more selective than azothioprine and is gaining
popularity for use in SLE as well as transplantation. It
will be discussed in more detail in the section regarding management of renal transplants (see below).
Cyclophosphamide carries an increased risk of congenital defects (1622%) and it should be discontinued
at least three months pre-conception. Rarely, it is indicated later in pregnancy for severe maternal disease.
Admission should be considered if the woman
develops worsening hypertension, deteriorating renal
function or proteinuria, superimposed pre-eclampsia
or polyhydramnios.
Anti-hypertensives
Careful monitoring and control of blood pressure both
pre-pregnancy and antenatally is important. Treatment
for hypertension is no different from the management
of pregnant women without renal disease, however the
threshold for treatment may be lower, since good
control of hypertension is important to preserve renal
function.
For control of hypertension, the drug of choice is
methyldopa, with nifedipine or hydralazine as secondline agents. Long-term use of hydralazine and methyldopa may rarely induce a SLE-like syndrome, but
they are not contraindicated in SLE. Beta-blockers
have been associated with impaired fetal growth
when use long-term throughout pregnancy and started
in the first trimester, although labetalol may be
used as third line treatment in the second or third
trimesters, or intra-partum parenterally for acute severe
hypertension.
The angiotensin-converting enzyme (ACE) inhibitors
should not be used in pregnancy because they may
cause oligohydramnios, hypocalvaria, renal tubular
dysgenesis, renal failure, hypotension, decreased skull
ossification in the fetus and an increased risk of
intrauterine death. Women on ACE inhibitors should
be swapped to an alternative agent, usually methyldopa, when pregnancy is confirmed. This does not
need to be done preconception as ACE inhibitors are
not associated with structural malformations in the
first trimester. There is less evidence available for the
use of angiotensin II receptor blockers in pregnancy,
but as they are similar to the ACE inhibitors, should
also be avoided.
Management of women with renal transplants
Most of the management is the same as detailed
above. Additional points concern the increased risk of
infection, side-effects of drugs and rejection.

An MSU specimen should be taken and sent at each

visit and any infection treated promptly. Some women
require prophylactic antibiotics. Cytomegalovirus
(CMV) titres should be checked in each trimester if the
woman is CMV negative at the onset of pregnancy.
If renal function is deteriorating, then additional
differential diagnoses are cyclosporin nephrotoxicity,
and acute and/or chronic rejection. Features of
acute rejection include fever, oliguria, graft swelling
and tenderness, and altered echogenicity of renal
parenchyma and blurring of corticomedullary junction
on ultrasound. The definitive diagnosis of rejection
is only possible with renal biopsy.
The levels of immunosuppressive drugs are usually
maintained at pre-pregnancy levels, although sometimes doses of cyclosporin need increasing. Women
will require reassurance regarding the relative safety of
their drugs, as reduction or cessation of immunosuppressive therapy may provoke rejection. Prednisolone
and azothioprine have already been discussed, and
the dose of the latter may be monitored via maternal
white-cell count. Other drugs include cyclosporin and
tacrolimus, both of which appear to be safe for use in
pregnancy, although plasma levels should be measured
regularly. Pregnancy success rates are similar in
women taking azathioprine and cyclosporin, but the
incidence of IUGR is higher (3040% versus 20%) in
women taking cyclosporin. MMF is generally contraindicated in pregnancy, as it is toxic in animals, and
the limited data available from human pregnancies
suggest an increased risk of malformations. However,
there is no pattern to the reported malformations and
very few reported cases are available for analysis. In
women where MMF is used because of an episode of
rejection and it is deemed to be the only drug to
adequately control disease or rejection, changing to a
safer alternative such as azathioprine in preparation for
pregnancy may not be appropriate. After counselling,
women may opt to go ahead with pregnancy despite
the unknown risk of teratogenesis, when balanced
against the risk of deterioration in renal function if
MMF is stopped.
Caesarean section is only required for obstetric indications, although the overall section rate is increased
compared to background rates. The renal allograft
does not obstruct vaginal delivery. Prophylactic antibiotics should be given to cover any surgical procedure,
including episiotomy.
Neonatal problems are largely related to prematurity, but also include thymic atrophy, transient leukopenia or thrombocytopenia, septicaemia, and CMV
and hepatitis B infection. Congenital abnormalities are
no more common in the offspring of mothers taking
anti-rejection doses of the earlier mentioned immunosuppressive drugs, apart from possibly MMF.
Lupus

Renal lupus in pregnancy

S Germain and C Nelson-Piercy

154

Acute renal failure in pregnancy

Incidence
Acute renal failure (ARF), on the background of
normal renal function, is rare in pregnancy in the West
(0.005%), although remains a common cause of
maternal mortality in the developing world. Transient
mild-to-moderate renal impairment is more common.
ARF usually presents post-partum. Pregnant women
with underlying renal disease, such as lupus nephritis,
are at increased risk of a number of complications that
can lead to acute on chronic renal failure.

Management
This obviously depends on the underlying cause, and
is generally the same as for the management of ARF in
non-pregnant individuals, although there are a few
points specific to pregnancy and pregnancy-related
conditions. Fluid overload must be prevented, especially in pre-eclampsia, because of the susceptibility of
these women to pulmonary oedema. Plasmapheresis is
not needed for HELLP syndrome, which usually
improves with conservative therapy.

Conclusion
Diagnosis
The causes of ARF in pregnancy are listed in Table 4.
Many are associated with a coagulopathy. The commonest cause of ARF in the context of pre-eclampsia
is HELLP (Haemolysis, Elevated Liver enzymes, and
Low Platelets) syndrome (about 50%).
The underlying cause of ARF may be obvious, for
example in the case of abruption and postpartum
haemorrhage, although abruption occurs in 16% of
women with HELLP syndrome and this may be the true
underlying cause. Blood loss may not be recognized or
may be underestimated, and hypotension may be absent
or masked by co-existent pre-eclampsia. If ARF develops, especially post-partum, in a woman with features
of pre-eclampsia, combined with a microangiopathic
haemolytic anaemia and thrombocytopenia, it may be
difficult to differentiate between thrombotic thrombocytopenic purpura (TTP)/haemolytic uraemic syndrome
(HUS), HELLP syndrome and acute fatty liver of
pregnancy (AFLP). Indeed the conditions are closely
related and HUS or AFLP may evolve from HELLP.
HELLP syndrome is far more common, and is characterized by abnormal liver function, a coaguloapthy (not
seen in HUS) and a lower grade haemolysis. Pointers
to HUS are profound thrombocytopenia, and florid
microangiopathic haemolytic anaemia. Features of
AFLP are abormal liver function, hypoglycaemia, high
uric acid, and profound coagulopathy.

Important physiological adaptations to pregnancy

present a challenge to the clinician managing women
with renal disease in pregnancy. Minor degrees of
renal impairment will be missed unless pregnancyspecific normal ranges for serum creatinine are used.
Lupus flares are more common in pregnancy and the
puerperium but they are harder to diagnose because
many of the symptoms, signs and laboratory abnormalities may occur in normal pregnancy. A particular
difficulty is the diagosis of pre-eclampsia which is
more common in lupus nephritis, when there is preexisting hypertension and worsening proteinuria.
Antiphospholipid antibodies increase the risk of capillary thrombotic microangiopathy in the kidney, renal
artery stenosis and adverse pregnancy outcome. Most
of the drugs used to manage SLE and after renal transplantation are safe in pregnancy. Pre-pregnancy counseling ensures thorough assessment of disease activity
and complications, and outcome for women with lupus
nephritis is optimal when disease has been quiescent
for at least six months at conception. Pregnancy in
these complicated women should be managed with
multidisciplinary care in combined clinics with
involvement from obstetricians, rheumatologists,
obstetric physicians, nephrologists, fetal medicine
practitioners, haematologists, neonatologists and
anaesthetists.

References
Table 4 Causes of acute renal failure in pregnancy
Infection
Blood loss
Volume contraction
Post-renal failure
Drugs
Other

Septic abortion; puerperal sepsis; pyelonephritis

Postpartum haemorrhage; placental abruption
Pre-eclampsia; eclampsia (6%); HELLP
syndrome (7%); hyperemesis gravidarum
Ureteric damage or obstruction
NSAIDs; antibiotics
HUS/TTP; AFLP (60%); glomerulonephritis

HELLP: haemolysis, elevated liver enzymes, and low platelets; NSAIDs:

non-steroidal anti-inflammatory drugs; HUS: haemolytic uraemic
syndrome; TTP: thrombotic thrombocytopenic purpura; AFLP: acute fatty
liver of pregnancy.
Lupus

1 Armenti VT, Radomski JS, Moritz MJ, Gaughan WJ, McGrory CH,
Coscia LA. Report from the National Transplantation Pregnancy
Registry (NTPR): outcomes of pregnancy after transplantation.
Clin Transpl 2003; 131141.
2 Davison J, Baylis C. Renal disease. In de Swiet M ed. Medical
Disorders in Obstetric Practice, 4th edn. Blackwell Science, 2002:
198266.
3 Epstein FH. Pregnancy and renal disease. N Engl J Med 1996; 335:
277278.
4 Hou SH. Pregnancy in women with chronic renal insufficiency and end
stage renal disease. Am J Kid Dis 1999; 33: 235252.
5 Jones DC. Hayslett JP. Outcome of pregnancy in women with moderate or
severe renal insufficiency. N Engl J Med 1996; 335: 226232.

Renal lupus in pregnancy

S Germain and C Nelson-Piercy

155
6 Jungers P, Houllier P, Forget D et al. Influence of pregnancy on the course
of primary chronic glomerulonephritis. Lancet 1995; 346: 11221124.
7 Jungers P, Chauveau D. Pregnancy in renal disease. Kidney Int 1997;
52: 871885.
8 Moroni G, Ventura D, Riva P et al. Antiphospholipid antibodies
are associated with an increased risk for chronic renal insufficiency
in patients with lupus nephritis. Am J Kidney Dis 2004; 43: 2836.

9 Moroni G, Ponticelli C. The risk of pregnancy in patients with lupus

nephritis. J Nephrol 2003; 16: 161167.
10 Ostenson M. Disease specific problems related to drug therapy in
pregnancy. Lupus 2004; 13: 746750.
11 Oviasu E, Hicks J, Cameron JS. The outcome of pregnancy in women
with lupus nephritis. Lupus 1991; 1: 1925.

Lupus

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.