1) Pregnancy causes physiological changes that affect the urinary system, increasing risks of urinary tract infections (UTIs). UTIs are commonly caused by E. coli and other bacteria and can lead to acute pyelonephritis if left untreated. 2) Asymptomatic bacteriuria, though not causing symptoms, increases risks of pyelonephritis and adverse pregnancy outcomes if left untreated. Screening and treatment reduces these risks. 3) Acute pyelonephritis is a serious infection requiring prompt treatment, usually intravenous antibiotics, to prevent maternal and fetal complications like preterm labor. Outpatient management may be appropriate for select cases.

1. Chapter 44
Renal Disorders
David J. Williams, PhD, and John M. Davison, MD
Among the many physiologic changes that occur in normal pregnancy, Escherichia coli (70% to 80%), Klebsiella, Proteus, Enterobacter, and
few are as profound as those affecting the urinary system.1 These Staphylococcus saprophyticus.
healthy alterations and various diagnostic pitfalls for the unwary clini- If urine from a symptomatic pregnant woman is cloudy and posi-
cian are discussed in Chapter 7. Improvements in our knowledge about tive on dipstick testing for nitrite (produced by most uropathogens)
gestational physiology in antenatal care generally, technology for fetal and leukocyte esterase (produced by white blood cells), a UTI is likely
surveillance, and neonatology services have meant better care and out- and empiric treatment can be started.9 These urine sticks are not sensi-
comes for women with renal problems and their newborns.2,3 With this tive enough to be used for screening for asymptomatic bacteriuria in
is mind, this chapter focuses on urinary tract infection (UTI), acute early pregnancy,10 and microscopy and culture of a clean catch mid-
and chronic renal disease in pregnancy, and the management of preg- stream urine sample is necessary. Hematuria and proteinuria are unre-
nant women on dialysis or with renal allografts. liable indicators of a UTI, but they are important signs of renal disease
(discussed later).
Urinary Tract Infection Asymptomatic Bacteriuria
The incidence of asymptomatic bacteriuria (i.e., significant growth of
a uropathogen in the absence of symptoms) is 2% to 10%, which is Maternal and Fetal Risks
the same during pregnancy as it is in sexually active nonpregnant During pregnancy, untreated asymptomatic bacteriuria will develop
women.4 However, the structural and immunologic changes to the into acute pyelonephritis in up to 30% of women, but if treated, less
urothelium of the renal tracts during pregnancy5 make it more likely than 1% of pregnant women develop pyelonephritis.4,6,7 A systematic
that a lower UTI will ascend to cause acute pyelonephritis.4,5 During review of 14 studies confirmed that antibiotic treatment of asymptom-
pregnancy, 12.5% to 30% of women with untreated asymptomatic atic bacteriuria significantly reduced the incidence of pyelonephritis
bacteriuria develop acute pyelonephritis,4,6-8 a serious infection with compared with placebo or no treatment (odds ratio [OR], 0.25; 95%
significant morbidity for the mother and fetus. confidence interval [CI], 0.14 to 0.48).11 After successful treatment of
asymptomatic bacteriuria, monthly screening of midstream urine is
necessary, because about 30% of women will have a relapse of bacte-
Diagnosis of Urinary Tract Infections riuria, making them vulnerable to acute pyelonephritis again.4
During pregnancy, symptoms suggesting a UTI are dysuria and offen- Asymptomatic bacteriuria has been associated with an increased
sive-smelling urine. Others usually associated with a UTI are urinary risk of preterm delivery and low birth weight.12 Treatment of asymp-
frequency, nocturia, urge incontinence, and strangury (i.e., the urge to tomatic bacteriuria has been shown to reduce the incidence of low-
pass urine having just done so), but these symptoms are also found in birth-weight infants (OR, 0.66; 95% CI, 0.49 to 0.89)11 but have no
healthy pregnant women. effect on preterm delivery.6 It has been suggested that the underlying
Microscopy and culture of a freshly voided midstream urine sample renal pathology, which is commonly associated with bacteriuria, is
allow quantification of pyuria (i.e., leukocytes in the urine) and growth responsible for poor pregnancy outcomes.6 Additional good-quality
of a urinary pathogen. A bacterial UTI is the most common cause of studies are needed to settle this issue.
pyuria and is considered significant if microscopy of a sample of
unspun midstream urine reveals more than 10 leukocytes per micro- Management of Asymptomatic Bacteriuria
liter. Urine culture is conventionally recognized as significant if there Contrary to much published advice, not all pregnant women need to
is growth of more than 105 colony-forming units per milliliter (CFU/ be screened for asymptomatic bacteriuria. There are two main reasons.
mL) of a single recognized uropathogen, in association with pyuria.9 First, the prevalence of asymptomatic bacteriuria varies between
Low counts of bacteriuria10 (24 to 104 CFU/mL) may still be significant populations, and where it is low (<2.5%), it is hard to justify the cost-
if symptomatic women have a high fluid intake or are infected with a effectiveness of screening. In populations in which the prevalence of
slow-growing organism. If left untreated, most symptomatic women asymptomatic bacteriuria is more than 5%, the case for screening is
with low-count bacteriuria will have 105 CFU/mL 2 days later.9 During much stronger.7 Second, approximately 1% to 2% of the 90% to 98%
pregnancy, the most common uropathogens are bowel commensals, of asymptomatic women who test negative for bacteriuria in the first

2. 906 CHAPTER 44 Renal Disorders
trimester will develop a symptomatic UTI.8,13 This means that one (>110 beats/min) at 20 weeks’ gestation or later and who have received
third of all women who develop a UTI in late pregnancy would have tocolytic agents and injudicious fluid replacement.23
been missed on first-trimester screening.8,13 Women at increased risk
for pyelonephritis or renal impairment should be screened for asymp- Fetal Risks
tomatic bacteriuria every 4 to 6 weeks throughout pregnancy. Acute pyelonephritis can trigger uterine contractions and preterm
labor.24 Antibiotic treatment of pyelonephritis reduces uterine activity,
but patients with recurrent infection or marked uterine activity are at
Treatment of Urinary Tract Infections increased risk for preterm labor.24 Because uterine activity often occurs
There is no consensus about the optimal treatment of asymptomatic in the absence of cervical change and because tocolysis with β-mimet-
bacteriuria14 or the empiric treatment of symptomatic UTIs in preg- ics aggravates the cardiovascular response to endotoxemia,23 tocolytic
nancy.15 Most urinary infections during pregnancy (approximately therapy should be used with care and only in those with cervical
75%) are caused by E. coli, which is usually sensitive to nitrofurantoin changes.25
(89%), trimethoprim with or without sulfamethoxazole (87%), ampi-
cillin (72%), or cephalosporins.16,17 Until well-structured trials are Management of Acute Pyelonephritis
done, the most cost-effective treatment for asymptomatic bacteriuria Women suspected of acute pyelonephritis from their history, symp-
or a first episode of cystitis is nitrofurantoin monohydrate macrocrys- toms, and signs should be admitted to the hospital. Laboratory tests
tals (100 mg twice daily for 3 days) or trimethoprim (200 mg twice should include a full blood cell count, serum creatinine concentration,
daily for 3 days).17 Nitrofurantoin should be avoided after the onset of levels of electrolytes, and urine culture. If there are systemic symptoms
labor in patients with glucose-6-phosphate dehydrogenase deficiency, or septic shock, a blood culture may be useful. Pregnant women
although no well-documented cases of hemolysis in neonates have with pyelonephritis and septic shock need intensive care. For these
been recorded,18 and trimethoprim should be avoided in the first tri- women, assessment of the state of hydration is critical and often
mester because it is a folic acid antagonist associated with an increased requires invasive hemodynamic monitoring with a central venous
risk of neural tube defect.19 pressure line. This can optimize fluid balance, aiming for a urine
Screening for recurrent infections should begin 1 week after com- output greater than 30mL/hr to minimize renal impairment and
pletion of initial treatment and then be done every 4 to 6 weeks for reduce the risk of pulmonary edema. Intravenous antibiotics should
the remainder of pregnancy. Recurrent infections or a first infection in be started empirically (discussed later) until the sensitivities of blood
a pregnant woman at high risk for pyelonephritis should be treated and urine cultures are known. These women often have transient
with a 7- to 10-day course of an antibiotic that reflects antibacterial renal impairment, thrombocytopenia, and hemolysis, suggesting that
sensitivities.17 Women who have had two episodes of asymptomatic the alveolar capillary endothelium is damaged by endotoxin.22 A blood
bacteriuria or cystitis should be considered for low-dose antibiotic film and lactate dehydrogenase concentration can be used to diagnose
prophylaxis—guided by the sensitivities of the most recent infective hemolysis.
organism—for the remainder of pregnancy and until 4 to 6 weeks after Trials investigating the outpatient management of pyelonephritis
birth.20 Suitable regimens for long-term antibiotic prophylaxis include in pregnancy have identified a group of women who can be managed
nitrofurantoin (50 to 100 mg each night), amoxicillin (250 mg each at home.25 These women should be less than 24 weeks’ gestation, be
night), cephalexin (125 to 250 mg each night), or trimethoprim (100 relatively healthy, and understand the importance of compliance. They
to 150 mg each night).20 These women should also be investigated for should have an initial period of observation in the hospital to demon-
structural abnormalities of the renal tracts or renal calculus using strate an ability to take oral fluids and receive intramuscular cefurox-
ultrasonography. ime or ceftriaxone. After satisfactory laboratory tests, they can go home
and are seen again within 24 hours for a second intramuscular dose of
cephalosporin. They then start a 10-day course of oral cephalexin
Acute Pyelonephritis (500 mg four times daily) or appropriate antibiotic with regular out-
The same uropathogens that cause asymptomatic bacteriuria and patient follow-up.24 Following this regimen, 90% of women will
cystitis are responsible for acute pyelonephritis.21 The prevalence of improve as outpatients, and 10% will require hospital admission
asymptomatic bacteriuria in a pregnant population dictates the inci- because of sepsis or recurrent pyelonephritis. Women with acute
dence of acute pyelonephritis. Screening and treating a high-risk popu- pyelonephritis who are beyond 24 weeks’ gestation should be admitted
lation for asymptomatic bacteriuria reduces the incidence of acute for at least 24 hours to observe the maternal condition as described
pyelonephritis to less than 1%.8,11 Unless acute pyelonephritis is treated earlier and to monitor uterine activity and the fetal heart rate.25
promptly, there is considerable maternal and fetal morbidity.21 Gram-negative bacteria causing pyelonephritis in pregnancy are
often resistant to ampicillin,26 and intravenous cefuroxime (750 mg to
Maternal Symptoms and Signs 1.5 gm, depending on severity of condition, every 8 hours) is an effec-
Most women with acute pyelonephritis present in the second or third tive first choice until culture sensitivities are known.15 Women allergic
trimester.21 More than 80% of women present with backache, fever, to β-lactam antibiotics can be given intravenous gentamicin (1.5 mg/
rigors and costovertebral angle tenderness, and about one half have kg every 8 hours) for the initial treatment of acute pyelonephritis.
lower urinary tract symptoms, nausea, and vomiting.21 Bacteremia A single-dose regimen (7 mg/kg every 24 hours) should be avoided
occurs in 15% to 20% of pregnant women with acute pyelonephritis,21 during pregnancy to reduce the very small risk of cranial nerve VIII
and a small proportion of these women will develop septic shock and damage to the fetus.17 Serum concentrations of gentamicin should be
increased capillary leak, leading to pulmonary edema.22 It is important, measured and dose adjustments made according to identified levels.
however, to differentiate the hypotension due to reduced intravascular Intravenous antibiotics should be continued until the patient has been
volume (i.e., fever, nausea, and vomiting) from that caused by septic afebrile for 24 hours. Oral antibiotics should then be given for 7 to 10
shock. Women with pyelonephritis at risk for serious complications days, according to bacterial sensitivities, or if not available, as if for
are those who present with the highest fever (>39.4 °C) and tachycardia symptomatic lower UTI.17

3. CHAPTER 44 Renal Disorders 907
Failure of these measures to improve the maternal clinical condition
within 48 to 72 hours suggests an underlying structural abnormality. Preeclampsia
Ultrasonography is an easy but inconclusive way of excluding stones. If
clinical suspicion is high, a plain abdominal radiograph can identify 90% Preeclampsia and the Kidney
of renal stones, and a one-shot intravenous urogram (IVU) at 20 to 30 Preeclampsia rarely causes acute renal failure severe enough to require
minutes can identify the remainder.25 The risk to the fetus from radiation dialysis.32 In a cohort of South African women with severe preeclamp-
of one or two radiographs is minimal, especially when compared with sia and renal impairment, 7 (10%) of 72 required temporary dialysis,
the clinical benefit of identifying an obstructed, nonfunctioning kidney. and none developed chronic renal failure.32 All women with severe
Urinary tract obstruction can also be detected using magnetic resonance preeclampsia who needed dialysis had hemorrhage, which often was
urography, especially during the second and third trimesters.27 caused by abruptio placentae.32 Preeclampsia causing mild transient
After one episode of pyelonephritis, pregnant women should have renal impairment (serum creatinine up to 125 μmol/L or 1.41 mg/dL)
monthly urine cultures to screen for a recurrence.25 The risk of recur- is common, but with appropriate management, there should be com-
rent pyelonephritis can be reduced with antimicrobial prophylaxis plete recovery of renal function.
chosen according to the sensitivities of initial bacterial infection20,28 or Women with preexisting renal disease are more vulnerable to pre-
with nitrofurantoin (100 mg every night) continued until 4 to 6 weeks eclampsia, especially when it is associated with chronic hypertension33
after delivery.25 (see Chapter 35). A meta-analysis of trials investigating the effective-
ness of low-dose aspirin (50 to 150 mg/day) in pregnant women with
moderate to severe renal disease revealed a significant reduction in the
risk of preeclampsia and perinatal death.34
Acute Renal Failure Conversely, 2% to 5% of women with preeclampsia are later found
in Pregnancy to have underlying renal disease,35 but if preeclampsia is severe, up to
20% of women will have chronic kidney disease (CKD).36 Women who
Acute renal failure has become a rare but serious complication of have had preeclampsia should therefore be checked for persistent
pregnancy. In early pregnancy, acute renal failure is associated with postpartum hypertension and proteinuria. Gestational hypertension
septic abortion (a complication largely confined to the developing usually resolves within 3 months of delivery, but severe proteinuria due
world) and dehydration related to hyperemesis gravidarum. Around to preeclampsia can take up to 12 months to disappear. Women who
the time of delivery, acute renal failure is most commonly caused by have had preeclampsia are more likely to have persistent microalbu-
gestational syndromes such as preeclampsia and abruptio placentae minuria compatible with microvascular disease and are at increased
(Table 44-1). However, pregnancy is a prothrombotic state that is asso- risk for cardiovascular disease in later life.37,38
ciated with heightened inflammation29 and major changes to the vas- Women who develop high levels of proteinuria (>10 g/24 hr) tend
cular endothelium,30 particularly the glomerular capillary endothelium.31 to have earlier-onset preeclampsia and deliver at an earlier gestational
These physiologic changes predispose pregnant women to acute glo- age compared with preeclamptic women who have less marked pro-
merular capillary thrombosis. Whereas nonpregnant patients who teinuria (<5 g/24 hr).39 After correction for prematurity, however,
suffer an acute prerenal insult (e.g., hemorrhage, dehydration, septic massive proteinuria (>10 g/24 hr) has no significant effect on neonatal
shock) may develop transient acute tubular necrosis if inadequately outcome.39 Increasing proteinuria is not therefore an indication for
treated, the same prerenal insult in pregnancy is more likely to develop delivery. We suggest that pregnant women who develop a proteinuria
into renal cortical necrosis with permanent renal impairment. This is level of more than 1 to 3 g in 24 hours accompanied by other maternal
even more likely to occur if a prerenal insult coexists with a pregnancy- risk factors for thrombosis should be considered for thromboprophy-
related condition that induces a consumptive coagulopathy or endo- laxis with enoxaparin (40 mg SC each day) or Fragmin (5000 units SC
thelial damage (e.g., preeclampsia). each day).
Management is aimed at identification and correction of the pre- The diagnosis of preeclampsia is difficult if there is chronic hyper-
cipitating insult and optimal fluid resuscitation, which is best guided tension and preexisting proteinuria, especially because these two
by monitoring the central venous pressure and pulmonary artery parameters become increasingly marked in late pregnancy. Hyperuri-
wedge pressure. If oliguria persists despite euvolemia with deteriorat- cemia and intrauterine growth restriction are common features of
ing renal function or fluid overload, fluid restriction followed by renal preeclampsia and chronic renal impairment, but the presence of
replacement therapy is indicated. increased levels of hepatic transaminases and thrombocytopenia
support a diagnosis of preeclampsia.40
TABLE 44-1 CAUSES OF ACUTE RENAL Preeclampsia: Management of Renal
FAILURE IN PREGNANCY Impairment and Fluid Balance
Most common causes Severe preeclampsia The cure for severe preeclampsia is delivery of the infant and placenta.
Placental abruption Delivery may halt the general progression of preeclampsia, but post-
Causes in early pregnancy Septic abortion partum maternal renal function usually deteriorates before improv-
Hyperemesis gravidarum ing.32 It is advisable to recommend delivery for women who have
Ovarian hyperstimulation syndrome preeclampsia and an increase in the serum creatinine concentration
Rare causes Amniotic fluid embolus
from about 70 μmol/L (0.79 mg/dL) to more than 120 μmol/L
Hemolytic uremic syndrome/
thrombotic thrombocytopenic (1.36 mg/dL) to prevent ongoing renal impairment.
purpura Fluid balance is critical to the management of acute renal failure
Acute fatty liver of pregnancy during pregnancy. Too little intravascular fluid leads to prerenal failure,
Acute obstruction of renal tracts which is especially damaging to chronically impaired kidneys, whereas
too much fluid risks pulmonary edema, adult respiratory distress syn-

4. 908 CHAPTER 44 Renal Disorders
drome, and maternal death.41 Transient oliguria (<100 mL over 4 hours) They are characterized by microangiopathic hemolytic anemia and
is a common observation in the first 24 hours after a healthy pregnancy. thrombocytopenia. The congenital and acquired forms of HUS/TTP
If a preeclamptic woman is not obviously hypovolemic and has a serum are more common in late pregnancy.46 Women with HUS/TTP develop
urea level of 5 mmol/L or less and serum creatinine level of 90 μmol/L platelet thrombi attached to von Willebrand factor multimers in end-
or less, repeated fluid challenges to increase urine output are unneces- organ microvessels. This typically results in a multiorgan disorder with
sary and increase the maternal risk of pulmonary edema. Women with abdominal ischemia and renal or neurologic impairment.47 A plasma
severe preeclampsia and renal impairment (i.e., serum creatinine level metalloprotease (ADAMTS13), which normally cleaves von Willebrand
of more than 120 μmol/L or 1.36 mg/dL) should have their fluid balance factor multimers to prevent microthrombi, is deficient in some women
guided by a central venous pressure catheter or, when available, a pul- with congenital HUS/TTP,48 and antibodies that neutralize ADAMTS13
monary artery flotation catheter on a high-dependency unit familiar have been found in women with acquired HUS/TTP.49
with this equipment.42 The rate of fluid replacement should take account HUS/TTP is more common in women (approximately 70% of
of central venous filling pressure, pulmonary wedge pressure, hourly cases) and more common in association with pregnancy (approxi-
urine output, and insensible loses. After the patient is euvolemic, the mately 13% of cases).46 During pregnancy, the levels of ADAMTS13
rate of intravenous fluid replacement should equal the previous hours’ fall progressively.50 This may explain why women with a congenital
urine output plus insensible losses; this is usually 30 mL/hr if the patient deficiency of ADAMTS13 or with other risk factors for thrombosis
is afebrile. The amount of intravenous fluid replacement can be reduced (e.g., obesity, thrombophilia) are predisposed to peripartum
after the mother can take oral fluid and her renal impairment starts to HUS/TTP.
improve. Intravenous fluid regimens that stick to a fixed hourly replace-
ment can lead to fluid overload in oliguric women and to reduced Hemolytic Uremic Syndrome, Thrombotic
intravascular volume in those having a diuresis. Fluid replacement Thrombocytopenic Purpura, and Preeclampsia
should include blood to replace blood loses and then isotonic sodium Preeclampsia shares many similarities with HUS/TTP. Both syndromes
chloride or compound sodium lactate (i.e., Hartmann’s solution). Dex- occur most frequently in the third trimester or immediately after
trose solutions are hypotonic and lead to maternal hyponatremia (5% delivery. It is, however, important to differentiate them, because
dextrose contains only 30 mmol/L of NaCl, compared with 150 mmol/L management is different. Women with HUS/TTP often present with
of NaCl in a 0.9% sodium chloride solution). gastrointestinal or neurologic abnormalities,46 and they are more likely
Low-dose “renal” dopamine infusion (3 μg/kg/min) was previously to have severe renal impairment, hemolysis, and thrombocytopenia
used to increase renal blood flow in people with acute renal failure, but compared with women who have preeclampsia. Because disseminated
it is no longer thought to be beneficial. It is recommended that once intravascular coagulation (DIC) is rare in HUS/TTP, the prothrombin
hypovolemia has been corrected, as judged by the central venous pres- time and kaolin clotting time are usually normal.47 Women with
sure or pulmonary wedge pressure, preeclamptic women with oliguria preeclampsia are also more likely to have elevated levels of hepatic
(<200 mL/12 hr) and a serum urea level higher than 14 mmol/L transaminases, heavy proteinuria, and abnormal clotting compared
(39 mg/dL) and serum creatinine level higher than 500 mmol/L with women with HUS/TTP.40 However, in many women, the
(5.65 mg/dL) may benefit from a furosemide infusion (5 mg/hr) in an distinction between preeclampsia and HUS/TTP can be determined
effort to prevent fluid overload and hemodialysis.43 only by the course of the illness after delivery,51 but acute renal failure
After acute tubular necrosis is established with oliguria and a rising due to preeclampsia usually becomes transiently worse before
serum creatinine level despite adequate intravascular volume and improving.32
blood pressure, fluid intake should be restricted to avoid fluid over-
load. In these circumstances, dialysis is indicated. There are no good Management of Hemolytic Uremic Syndrome
studies that have followed up women with acute renal failure related and Thrombotic Thrombocytopenic Purpura
to preeclampsia, but those with the most severe renal impairment will Maternal survival from HUS/TTP greatly improved since treatment
undoubtedly be left with a degree of permanent renal impairment that with plasmapheresis (i.e., infusion of fresh plasma and removal of old
may not manifest until later life.32 plasma).52 Until recently, it was unclear why plasmapheresis worked,
Hypertension due to preeclampsia is caused by vasoconstriction but the discovery of antibodies to ADAMTS13 (removed with old
around a reduced plasma volume.40 For this reason and despite the lack plasma) and a congenital deficiency of ADAMTS13 (replenished with
of evidence from randomized trials, women with severe preeclampsia infusion of fresh plasma) gives reason to this process. However, severe
often receive plasma volume expansion before therapeutic vasodila- deficiency of ADAMTS13, which is not a routine laboratory measure-
tion. Unless there are signs of pulmonary edema (i.e., basal crackles ment, is not present in all cases of HUS/TTP, and plasmapheresis
and PO2 < 95% on air), 500 mL of colloid or crystalloid given over 30 is effective in pregnant women who have milder deficiencies of
to 60 minutes or 250 mL per hour until the pulmonary wedge pressure ADAMTS13.53
is 10 to 12 mm Hg can improve maternal and fetal well-being in cases Steroids are often added to the plasma exchange regimen and are a
of severe preeclampsia.45,46 A vasodilator given alone can cause pro- rationale choice for acquired HUS/TTP with an autoimmune pathol-
found hypotension that may threaten maternal renal, cerebral, and ogy, but there are no randomized, controlled trials of their use. Anti-
uteroplacental blood flow. platelet regimens with aspirin and dipyridamole may also be beneficial
in conjunction with plasma exchange.54 Conversely, administration of
platelets to thrombocytopenic patients with HUS/TTP can result in a
Hemolytic Uremic Syndrome precipitous decline in clinical status.
and Thrombotic
Thrombocytopenic Purpura Acute Renal Cortical Necrosis
Hemolytic uremic syndrome (HUS) and thrombotic thrombocytope- In the developed world, acute renal cortical necrosis (ARCN) has
nic purpura (TTP) are similar syndromes (designated HUS/TTP). become a rare complication of pregnancy. The reduced incidence of

5. CHAPTER 44 Renal Disorders 909
septic abortion and improved management of peripartum obstetric
emergencies have prevented prerenal impairment developing into Nephrotoxic Drugs during Pregnancy
acute tubular necrosis and then renal cortical necrosis. In the develop- Nonsteroidal anti-inflammatory drugs (NSAIDs), including the more
ing world, however, obstetric emergencies are still responsible for most selective cyclooxygenase-2 (COX-2) inhibitors, when given to the
cases of ARCN.55 Acute renal failure after septic abortion or peripar- mother in the peripartum period, reduce renal blood flow and have
tum obstetric emergencies developed into ARCN in 20% of women been associated with acute renal impairment in the mother and fetus.61
after a prolonged period of acute tubular necrosis.56 Women with reduced intravascular volume, especially with preexisting
ARCN is most commonly caused by abruption of the placenta with renal impairment, are particularly vulnerable and should be prescribed
hemorrhage, amniotic fluid embolus, and sepsis associated with DIC.57 NSAIDs with caution. Aminoglycosides are also nephrotoxic and
After hemorrhage or sepsis with hypotension, prerenal failure without should be prescribed with care and attention to drug plasma levels in
adequate resuscitation leads to acute tubular necrosis. If anuria persists women with mild renal impairment.
for longer than a week, ARCN should be suspected. A definitive diag-
nosis can be made with renal biopsy, but it is often missed because of
the patchy nature of cortical necrosis. Selective renal angiography can
confirm the diagnosis, but it introduces another nephrotoxic agent and Acute Renal Obstruction in Pregnancy
is usually unnecessary. Because of the serious nature of the precipitat- The renal tracts may be obstructed during pregnancy by renal calculi
ing illness and the limited availability of renal replacement therapy in (discussed later), congenital renal tract abnormalities, or a gestational
the developing world, the maternal mortality rate is still high.56 overdistention syndrome. Women born with congenital obstructive
For women who survive the acute illness, renal function usually uropathies at the pelviureteral junction (PUJ) or vesicoureteric junc-
returns slowly over the next 6 to 24 months. Long-term renal function tion (VUJ) are at increased risk of urine outflow obstruction in the
depends on the extent of cortical necrosis, which is often incomplete. second half of pregnancy, even if they have had surgical correction in
Hyperfiltration through remnant glomeruli usually leads to a subse- childhood.62 Congenital abnormalities of the lower urinary tracts,
quent progressive decline in renal function. including the bladder and urethra, are varied and usually require
extensive surgical correction in childhood. During pregnancy, these
women are at increased risk for recurrent urine infections and, less
Acute Fatty Liver of Pregnancy commonly, for outflow obstruction requiring temporary nephrostomy
Acute fatty liver of pregnancy (AFLP) causes reversible peripartum or a ureteric stent.63
liver and renal impairment in 1 of 5000 to 10,000 pregnancies.58 The Women with a single kidney and urologic abnormalities are par-
diagnosis is based on clinical and laboratory findings of impaired liver, ticularly vulnerable to develop post-renal failure in relation to gesta-
renal function, and clotting function, rather than on histologic or tional obstruction of their solitary kidney. An incomplete obstruction
radiologic evidence of a fatty liver.58 Women with AFLP usually present can cause renal impairment with an apparently good urine output.
with nausea, vomiting, and abdominal cramps. Impaired renal func- High backpressures compress and damage the renal medulla, leading
tion and reduced plasma antithrombin levels are early findings of to a loss of renal concentrating ability and production of dilute urine
AFLP that may precede liver dysfunction.58 In established cases of that is passed through an incomplete obstruction. It is also important
AFLP, depressed function of the liver with prolonged prothrombin for the obstetrician to remember that a congenitally single kidney is
time, hypoglycemia, and DIC are more markedly abnormal than levels often associated with other abnormalities of the genital tracts, such as
of liver transaminases, which may only be moderately elevated.58 In a a unicornuate uterus.64
series of 28 women with AFLP, other ubiquitous laboratory findings at During pregnancy, the renal tracts can rarely and spontaneously
the time of delivery were elevated levels of serum total bilirubin (mean, become grossly overdistended. If untreated, overdistention occasion-
7.5 mg/dL), serum creatinine (mean, 205 mmol/L or 2.3 mg/dL), and ally can lead to rupture of the kidney or renal tracts.65 Women with
uric acid (mean, 11 mg/dL).58 overdistention of the renal tracts initially present with severe loin pain,
A recessively inherited fetal inborn error of mitochondrial fatty acid most commonly on the right side and radiating to the lower abdomen.
oxidation may explain up to 20% of AFLP cases.59 Mitochondrial fatty The pain is positional and inconstant; it is characteristically relieved
acid oxidation is important for normal renal and liver function and by lying on the opposite side and tucking the knees up to the chest. A
may therefore explain the dual vulnerability of these organs in women palpable tender flank mass may suggest renal tract rupture.65 Rupture
with AFLP. of the kidney almost always occurs in a previously diseased kidney,
In women with AFLP, maternal renal impairment is aggravated by usually in association with a benign hamartoma or renal abscess.65
hypotension from hemorrhage, which is most likely to follow an emer- Urinalysis can reveal gross or microscopic hematuria. A renal ultra-
gency operative delivery.58,60 The combination of renal dysfunction, sound can detect a hydronephrotic kidney with a grossly dilated
hemorrhage, and DIC resulting from liver failure during pregnancy or pelvicaliceal system. Occasionally, a urinoma is evident around the
after delivery requires intensive care with a multidisciplinary team of kidney, indicating rupture of the renal pelvis that can sometimes seal
hepatologists, nephrologists, intensive care specialists, and obstetri- spontaneously.
cians. Management is supportive and aimed at maintaining adequate The pain from the overdistention syndrome varies from mild
fluid balance for renal perfusion, replacing blood, correcting the coag- to very severe. Women with mild symptoms can usually be managed
ulopathy with fresh frozen plasma and possibly with antithrombin with advice on positional relief and regular analgesia. Women with
concentrate and fresh platelets. Hypoglycemia should be corrected severe unremitting pain, hematuria, and grossly distended renal tracts
with 10% dextrose solutions. Temporary dialysis may be necessary, but on ultrasound in the absence of structural or infected masses usually
with good supportive care, recovery of normal renal and liver function have immediate pain relief after decompression of the system with
is usual.58 Perinatal survival in association with AFLP is improving, but a ureteric stent or nephrostomy. Rupture of the kidney necessi-
it depends on the early recognition of the maternal condition, close tates immediate surgery and almost invariably an emergency
fetal surveillance, timely delivery, and excellent neonatal care. nephrectomy.65

6. 910 CHAPTER 44 Renal Disorders
TABLE 44-2 STAGES OF CHRONIC KIDNEY
Chronic Kidney Disease DISEASE
Normal Pregnancy and Stage Description GFR*
Renal Assessment 1 Kidney damage with normal or ≥90
increased GFR
The glomerular filtration rate (GFR), measured as 24-hour creatinine 2 Kidney damage with mildly 60-89
clearance, increases by more than 50% shortly after conception. decreased GFR
Serum creatinine (and urea nitrogen levels, which average 70 μmol/L 3 Moderately decreased GFR 30-59
(0.8 mg/dL) and 5 mmol/L (13 mg/dL), respectively, in nonpregnant 4 Severely decreased GFR 15-29
women, decrease to mean values of 50 μmol/L (0.6 mg/dL) and 5 Kidney failure <15 or dialysis
3 mmol/L (9 mg/dL) in pregnant women. Near term, a 15% to 20%
*Glomerular filtration rate (GFR) reported as mL/min/1.73 m2.
decrement in GFR occurs, which affects serum creatinine levels
From the National Kidney Foundation: K/DOQI clinical practice
minimally. guidelines for chronic kidney disease: Evaluation, classification and
Serum creatinine values of 80 μmol/L (0.9 mg/dL) and urea nitro- stratification. Am J Kidney Dis 39(Suppl 1):S1-S266, 2002.
gen of 6 mmol/L (14 mg/dL), which are acceptable in nonpregnant
subjects, are suspect in pregnant women. However, the physician
should use caution in assessing renal function by serum creatinine Women with CKD are less able to make the renal adaptations
levels alone, because the creatinine is filtered and secreted by the characteristic of and essential to healthy pregnancy. Their inability to
kidney, and the ratio of creatinine to inulin clearance normally falls to boost renal hormones often leads to normochromic normocytic
between 1.1 and 1.2. As renal disease progresses, a greater portion of anemia, reduced plasma volume expansion, and vitamin D defi-
urinary creatinine is formed as a result of secretion (clearance ratios ciency.75,76 The gestational rise in GFR is impaired in women with
rise to between 1.4 and 1.6 when the serum creatinine level is 1.4). The moderate renal impairment and usually absent in those with a serum
GFR may be overestimated by 50%. creatinine level higher than 200 μmol/L (2.26 mg/dL).68,77,78 If pre-
Formulas (e.g., the Cockroft-Gault formula) that use serum creati- eclampsia develops there is often a mild deterioration in renal func-
nine in relation to age, height, and weight to calculate GFR should not tion, but the addition of a prerenal insult, such as significant peripartum
be used in pregnancy because weight or body size does not reflect hemorrhage, can seriously threaten maternal renal function.
kidney size. The use of estimated GFR (eGFR) from the Modification
of Diet in Renal Disease (MDRD) formula, whereby the serum creati-
nine value is adjusted for age, gender, and race, cannot be recom- Renal Dysfunction and the Impact
mended for use in pregnancy because it significantly underestimates of Pregnancy
the GFR.66 Ideally, evaluation of renal function in pregnancy should be
based on the clearance of creatinine rather than its serum concentra- Mild Renal Impairment: Chronic Kidney Disease
tion. Creatinine levels may increase by up to 12 μmol/L (0.15 mg/dL) Stages 1 and 2
shortly after ingestion of cooked meat (because cooking converts pre-
formed creatine into creatinine), and the timing of the blood sample Most women with CKD who become pregnant have mild renal dys-
during a clearance period must take into account meals and their function, and pregnancy usually succeeds without affecting renal prog-
content. nosis. However, complications such as preeclampsia, intrauterine
fetal growth restriction, and preterm birth are more common (Table
44-3).69,68
Renal Dysfunction and A case-controlled study of 360 women with primary glomerulone-
Preconception Counseling phritis and only mild pre-pregnancy renal dysfunction (serum creati-
CKD is often clinically and biochemically silent until renal impair- nine level less than 110 μmol/L), minimal proteinuria (<1 g/24 hr),
ment is advanced. Symptoms are unusual until GFR declines to less and absent or well-controlled hypertension, showed that pregnancy
than 25% of normal, and more than 50% of renal function can be lost had little or no adverse effect on long-term (up to 25 years) maternal
before the serum creatinine level rises above 120 μmol/L (1.36 mg/dL). renal function.79 The situation is quite different for women who have
However, women who become pregnant with a serum creatinine level moderate to severe renal impairment (CKD stages 3, 4, or 5).
above 125 μmol/L (1.4 mg/dL) are at increased risk for an accelerated
decline in renal function and poor pregnancy outcome.67-70 Moderate to Severe Renal Impairment: Chronic
CKD is universally classified into five stages according to the level Kidney Disease Stages 3 through 5
of renal function (i.e., GFR) (Table 44-2). CKD stages 3 through 5 Small, mainly uncontrolled, retrospective studies have shown that
(GFR < 60 mL/min) affect approximately 1 in 250 women of child- women with the worst pre-pregnancy renal function are at greatest risk
bearing age (20 to 39 years),71 but due to reduced fertility and an for an accelerated decline in renal function caused by pregnancy (see
increased rate of early miscarriage, pregnancy in these women is less Table 44-3). Proteinuria and hypertension add to this risk.68,70,77,80,81
common. Studies of CKD in pregnancy have mostly classified women One retrospective series of women with CKD (87 pregnancies) found
on the basis of serum creatinine values, but we estimate that approxi- that those with initially moderate renal impairment (serum creatinine
mately 1 of 750 pregnancies are complicated by CKD stages 3, 4, or level of 124 to 168 mmol/L or 1.4 to 1.9 mg/dL) had a 40% risk of a
5.72,73 Some women are discovered to have CKD for the first time pregnancy-related decline in renal function, which persisted after
during pregnancy. Approximately 20% of women who develop early delivery in about one half of those affected, whereas 13 (65%) of 20
preeclampsia (≤30 weeks’ gestation), especially those with heavy pro- women with severe renal impairment (i.e., serum creatinine level
teinuria, have previously unrecognized CKD.74 higher than 177 mmol/L or 2.0 mg/dL) had a decline in renal function

7. CHAPTER 44 Renal Disorders 911
TABLE 44-3 PRE-PREGNANCY RENAL FUNCTION IN CHRONIC RENAL DISEASE WITH ESTIMATES FOR
PREGNANCY OUTCOME (>24 WEEKS) AND IMPACT ON MATERNAL RENAL FUNCTION
Loss of Renal Function*
Serum Creatinine
Level
IUGR Preterm Delivery Preeclampsia Perinatal Deaths Pregnancy Persists after Delivery ESRF in 1 Year
mmol/L (mg/dL)
(%) (%) (%) (%) (%) (%) (%)
<125 (<1.4) 25 30 22 1 2 — —
125-180 (1.4-2.0) 40 60 40 5 40 20 2
>180 (>2.0) 65 >95 60 10 70 50 35
*Estimates are based on literature from 1985 to 2007, with all pregnancies attaining at least 24 weeks’ gestation.
ESRF, end-stage renal function; IUGR, intrauterine growth restriction.
Data from references 67-70, 72, 77, 78, 83, 165-169.
during the third trimester that persisted in almost all and deteriorated and infection increase the risk of complications at all levels of renal
to end-stage renal failure in 7 (35%) of 20.67,82 impairment.
The first prospective study to assess the rate of decline of maternal A question should be asked: Is pregnancy advisable? If a woman
renal function before and after pregnancy in 49 women with pre-preg- with chronic renal disease wishes to have a family, the sooner she starts,
nancy CKD stages 3 to 5 confirmed these earlier observations.70 Spe- the better. In some of these patients, renal function continues to decline
cifically, women with a pre-pregnancy eGFR less than 40 mL/min/1.73 m2 with time. Women are not always counseled before conception. A
and proteinuria level of more than 1 g in 24 hours, but not either factor patient with suspected or known renal disease may present already
alone, showed an accelerated decline in renal function after their preg- pregnant, and the question then becomes whether to continue the
nancy compared with before pregnancy. Chronic hypertension, which pregnancy.
predisposes women to preeclampsia, may explain why those with Ideally, all women with CKD should be made aware of the risks
milder renal dysfunction also have a gestational decline in renal func- pregnancy may have on their own long-term renal function and preg-
tion. This risk is reduced when hypertension is controlled. nancy outcome before they conceive. Folic acid (400 mg daily) should
be given as usual around conception until at least 12 weeks’ gestation.
Low-dose aspirin (50 to 150 mg/day) should be started in early preg-
Impact of Chronic Kidney Disease on nancy to reduce risk of preeclampsia and improve perinatal outcome.34
Perinatal Outcome Regular drugs should be reviewed so that fetotoxic drugs (e.g., angio-
Maternal hypertension, proteinuria, and recurrent urinary infection tensin-converting enzyme [ACE] inhibitors, angiotensin II receptor
often coexist in women with CKD, and it is difficult to apportion the blockers) can be stopped as soon as pregnancy is confirmed.85
contribution that each factor makes to a poor pregnancy outcome. It There are reports of women with severe chronic renal failure having
appears, however, that each factor is individually and cumulatively successful pregnancies managed without dialysis.86 In one woman, the
detrimental to fetal outcome.67,70,76,77 Although women with severe serum creatinine level was 700 μmol/L (8 mg/dL) at the time of spon-
renal impairment have the greatest difficulty conceiving, the highest taneous delivery.87 Dialysis has also been instituted prophylactically
rate of miscarriage, and poorest fetal outcome, there is a spectrum during pregnancy to increase the chances of a successful outcome.88
of poor outcomes, including preeclampsia, fetal growth restriction, Nevertheless, we believe that these women should not take additional
preterm delivery, and perinatal death, correlating with the level of renal health risks. The aim should be to preserve what little renal function
dysfunction.68,69,70,78,83 remains and to achieve renal rehabilitation by dialysis and transplanta-
tion, after which the question of pregnancy can be considered if
appropriate.
Preconception Counseling The literature that forms the basis of our views is primarily retro-
Initiating and sustaining pregnancy are related to the degree of func- spective. Most patients described had only mild dysfunction, and
tional impairment. Fertility is diminished as renal function falls. When women with greater dysfunctional disease were limited in number.
the preconception serum creatinine level exceeds 280 μmol/L (3 mg/ Confirmation of any preconception guidelines requires definitive
L), corresponding to a GFR of less than 25 mL/min, normal pregnancy observational trials that must be prospective.
is unusual; however, successes have been documented in women with
moderate to severe disease, including some treated with dialysis because
of accelerated maternal renal deterioration.84 Antenatal Strategy and
Ideally, pregnancy is probably best restricted to women with pre- Decision Making
conception serum creatinine levels below 180 μmol/L (2 mg/dL) and
a diastolic blood pressure of 90 mm Hg or less. If the patient has Patients should be seen at least at 2-week intervals or less until 32
hypertension requiring more than one drug for control, prognosis weeks’ gestation, after which assessment should be weekly. Routine
becomes substantially poorer. Some clinicians extend this limit serial antenatal observations should be supplemented with the
to 250 μmol/L (2.8 mg/dL), whereas others believe it should be following:
no higher than 140 μmol/L (1.5 mg/dL). Whatever level is used, we
reiterate that degrees of impairment not causing symptoms or disrupt- 1. Assessment of renal function using serum creatinine levels and
ing homeostasis in nonpregnant individuals can still jeopardize preg- protein excretion using the protein to creatinine ratio on a spot
nancy. Clinical complications such as hypertension, proteinuria, urine sample on approximately a monthly basis

8. 912 CHAPTER 44 Renal Disorders
2. Careful monitoring of blood pressure for early detection of hyper- of fluid balance, renal function, and blood pressure and a further
tension and treatment to keep blood pressure at 140/90 mm Hg or review of drug therapy are necessary. Breastfeeding should be encour-
less aged in women with CKD, but is sometimes not possible for those with
3. Early detection of superimposed preeclampsia, with checks of blood severe CKD. Information is still lacking on whether some immunosup-
urea nitrogen, full blood cell count, liver function tests, blood pres- pressive drugs appear in breast milk, but prednisolone, azathioprine,
sure, and proteinuria and ACE inhibitors are barely detectable in breast milk. Women who
4. Biophysical assessment of fetal size, development, and well-being have heavy proteinuria associated with preeclampsia should be fol-
5. Early detection of asymptomatic bacteriuria or confirmation of lowed until the proteinuria disappears or a diagnosis of renal disease
UTI every month is made.
Renal Function
If renal function deteriorates, reversible causes should be sought, such
as a UTI, subtle dehydration, or electrolyte imbalance, which is occa- Problems Associated with
sionally precipitated by inadvertent diuretic therapy. Near term, a 15%
to 20% decrement in function, which affects serum creatinine levels
Specific Kidney Diseases
minimally, is permissible. Failure to detect a reversible cause of a sig- In 1991, Imbasciati and Ponticelli90 reviewed outcomes for more than
nificant decrement is reason to end the pregnancy by elective delivery. 1000 patients with a variety of specific disorders, which were usually
When proteinuria occurs and persists but blood pressure is normal and documented by kidney biopsy. In this review and in other editorials,3
renal function is preserved, the pregnancy can be allowed to continue. therapeutic abortions were excluded from calculation of pregnancy
success rates and the discussion of the underlying factors.
Blood Pressure
Most of the specific risks of hypertension appear to be mediated
through superimposed preeclampsia. There is still controversy about Acute and Chronic Glomerulonephritis
the incidence of preeclampsia in women with preexisting renal disease. The acute form of glomerulonephritis is a rare complication of preg-
The diagnosis cannot be made with certainty on clinical grounds alone nancy, and it can be mistaken for preeclampsia. For patients with
because hypertension and proteinuria may be manifestations of the chronic glomerulonephritis, one view warns of aggravation because of
underlying renal disease. Treatment of hypertension in pregnancy is the hypercoagulable state accompanying pregnancy, with patients
considered in Chapter 35. more prone to superimposed preeclampsia or hypertensive crises
High blood pressure in the presence of an underlying kidney dis- earlier in pregnancy. The consensus, however, is that if renal func-
order is treated more aggressively than are other hypertensive compli- tion is stable and hypertension is absent, most pregnancies are suc-
cations of pregnancy. This is done because such actions preserve cessful.76 In a review of 906 pregnancies in 557 women, these
function longer. Although diastolic levels of 100 mm Hg or less may generalizations were endorsed90 and several specific issues were
be permissible in many pregnant women with underlying essential highlighted:
hypertension, a diastolic goal of 90 mm Hg or less should be set for
patients with renal disease. Complications developed more frequently in women who
already had some dysfunction or hypertension in early
Fetal Surveillance and Timing of Delivery pregnancy.
Serial assessment of fetal well-being is essential because renal disease De novo hypertension or worsening of preexisting
can be associated with intrauterine growth restriction, and when com- hypertension occurred in 25% of pregnancies but usually
plications do arise, the judicious moment for intervention is influenced reverted after delivery, suggesting superimposed preeclampsia,
by fetal status. Current technology should minimize the risk of intra- a diagnosis that is not easy to confirm in this group of patients.
uterine fetal death and neonatal morbidity and mortality. Regardless In 10% of pregnancies, hypertension persisted after delivery,
of gestational age, most infants weighing 1500 g or more are better off especially in patients with focal and segmental
in a special care nursery than in a hostile intrauterine environment. glomerulosclerosis, membranoproliferative glomerulonephritis,
Deliberate preterm delivery may be necessary if renal function deterio- and IgA nephropathy.
rates substantially or for the usual maternal and fetal causes, such as Higher rates of fetal loss observed in these women can be
uncontrollable hypertension, and signs adduced by monitoring of fetal accounted for by the greater prevalence of severe hypertension
jeopardy. and renal insufficiency.
Renal Biopsy Other, smaller series have endorsed these points. For example, preg-
Percutaneous renal biopsy is usually avoided in pregnancy because the nancy is well tolerated without effect on the course of the disease if
plethoric kidney appears to be more prone to bleeding, especially in blood pressure is normal and the GFR is higher than 70 mL/minute
hypertensive pregnant women.89 Renal biopsy, although not usually before conception.76,91 With hypertension, the rate of live births is
required for the diagnosis and management of preeclampsia, may be reduced if hypertension exists before pregnancy or is not well con-
indicated if there is reason to suspect a renal lesion that could be suc- trolled during gestation.
cessfully treated, especially in early pregnancy and up to 32 weeks’ Hereditary nephritis, an uncommon disorder, may first manifest or
gestation, whilst permitting the pregnancy to continue. become exacerbated during pregnancy, but most gestations succeed.
One variant of hereditary nephritis involves disordered platelet mor-
Postpartum Care phology and function. In these cases, pregnancy has been successful
It can take up to 3 months (occasionally longer) for the physiologic but was sometimes complicated by bleeding problems, especially at
changes of pregnancy to disappear. During that time, close monitoring delivery.

9. CHAPTER 44 Renal Disorders 913
pain or fever, and when the pregnancy is over, the usual x-ray evalua-
Chronic Pyelonephritis tion is obtained and standard management resumed.97
Chronic pyelonephritis (i.e., tubulointerstitial disease) in pregnancy Sonographically guided percutaneous nephrostomy is another
may be infectious or noninfectious. The prognosis in pregnancy is effective and safe method of treating gravidas with ureteric colic or
similar to that for patients with glomerular disease; the outcome is best symptomatic obstructive hydronephrosis. The procedure is rapid,
for patients with adequate renal function and normal blood pressure. requires minimal anesthesia, and is preferable to retrograde stenting
Compared with nonpregnant women, pregnant women have a higher or more invasive surgery.
frequency of symptomatic infections, but these patients may have In patients with cystinuria, assiduous maintenance of high fluid
a more benign antenatal course than do women with glomerular intake is the mainstay of management. Although D-penicillamine
disease. appears relatively safe, it should be used only for severe cases, such as
when urinary cystine excretion is known to be very high.98
Reflux Nephropathy
Autosomal Dominant Polycystic
The term reflux nephropathy is used to describe renal morphologic and
functional changes that relate to past (and usually present) vesicoure- Kidney Disease
teric reflux, which often is complicated by recurrent infection. Opin- Autosomal dominant polycystic kidney disease (ADPKD) is the most
ions were once controversial, but with preserved renal function and no common genetic renal disorder, but it may remain undetected during
hypertension, fetal and maternal outcomes appear to be excellent.77 For pregnancy. Careful questioning for a history of familial problems
these patients, vigilance is still necessary to detect and treat UTIs (28% and the use of ultrasonography may lead to earlier detection. Patients
to 65%), with many physicians advocating prophylactic antibiotics. do well when functional impairment is minimal and hypertension
Unfortunately, reflux nephropathy is often associated with hyperten- is absent, as is often the case in childbearing years.99 They do,
sion and moderate or severe renal dysfunction by the time these however, have an increased incidence of hypertension late in preg-
patients reach childbearing age, and such a scenario adversely affects nancy and a higher rate of perinatal mortality compared with that
pregnancy outcome. Specific obstetric concerns about affected patients in pregnancies of sisters unaffected by this autosomal dominant
include severe intrauterine growth restriction and the risk of sudden, disease.
rapid worsening of hypertension and renal function with accelerated Women with advanced renal failure are best advised against preg-
progression to renal failure.92 nancy, although use of prophylactic dialysis has been advocated, despite
lack of controlled studies, for this type of patient.100 If one or the other
prospective parent has evidence of polycystic renal disease, the couple
Urolithiasis may seek genetic counseling. There is a 50% chance of transmitting
The prevalence of urolithiasis in pregnancy is 0.03% to 0.35%.93 Renal the disease to the offspring, which is caused by two identified genes:
and ureteric calculi cause nonuterine abdominal pain severe enough PKD1 (85%) and PKD2 (15%). DNA probe techniques can make the
to necessitate hospital admission during pregnancy. Most calculi are diagnosis of ADPKD, but a significant number of ADPKD mutations
calcium oxalate (the more benign type), but occasionally, the more are caused by multiple amino acid substitutions, which need to be
malicious struvite stones (e.g., staghorn) are seen. Uric acid and cystine interpreted with caution.101
are much less common.
Management should be conservative initially, with adequate hydra-
tion, appropriate antibiotic therapy, and pain relief with systemic anal- Diabetic Nephropathy
gesics. Most women pass their stones spontaneously. The use of Because many patients have had diabetes since childhood, they
continuous segmental (T11 to L2) epidural block has been advocated, probably already have microscopic changes in the kidneys.102 During
as in nonpregnant patients with ureteric colic, and it may favorably pregnancy, diabetic women have an increased prevalence of covert
influence spontaneous passage of the stones. With good pain relief, bacteriuria (and may be more susceptible to symptomatic UTI),
patients micturate without difficulty, move without assistance, and are peripheral edema, and preeclampsia.84
less at risk for thromboembolic problems than if they are drowsy, Most women with diabetic nephropathy who become pregnant still
nauseated, and bedridden with pain. have good renal function and demonstrate normal GFR increments
When there are complications that may require surgical interven- (with perhaps significant proteinuria), and pregnancy does not accel-
tion, pregnancy should not be a deterrent to limited IVU, even though erate renal deterioration.103 There is, however, a report of diabetic
the clinician may be reluctant to consider radiologic investigation. women with moderate renal dysfunction (serum creatinine level above
Specific clinical criteria should be met before a limited IVU is under- 125 μmol/L or ≤1.4 mg/dL) whose renal function permanently deteri-
taken: microscopic hematuria, recurrent urinary tract symptoms, and orated in pregnancy compared with the changes before and after-
sterile urine culture when pyelonephritis is suspected. The presence ward.104 Such changes occurred despite good metabolic control and
of two of these criteria indicates a diagnosis of calculi in 60% of might have been related to hypertension, which often accelerates in the
women.94 third trimester regardless of intensified treatment.105 However, there
Magnetic resonance urography can be used to avoid radiation were no controls for this study. The condition of diabetic patients with
exposure.95 Another approach involves the cystoscopic placement of an creatinine levels above 1.4 mg/dL who do not become pregnant often
intraureteral tube, or stent, between the bladder and kidney under local progresses rapidly to further renal failure.
anesthesia.96 The stent retains its position because it has a pigtail or J- Hypertension should be treated more intensively in diabetics. As
like curve at each end (double-J), and it can be changed every 8 weeks with other renal disorders during pregnancy, we believe that more
to prevent encrustation. Early empiric use for presumed stone obstruc- aggressive antihypertensive therapy is a reasonable objective. These
tion in pregnant women with flank pain is recommended by some, patients often are treated with “renoprotecting” ACE inhibitors or
especially when hydration, analgesia, and antibiotics do not resolve angiotensin receptor blockers prescribed before conception, but

10. 914 CHAPTER 44 Renal Disorders
these drugs should be stopped as soon as possible after conception
to avoid teratogenic effects that become evident after 6 weeks’ Systemic Sclerosis
gestation.85 Scleroderma is a term that includes a heterogeneous group of limited
and systemic conditions causing hardening of the skin. Systemic scle-
rosis implies involvement of skin and other sites, particularly certain
Systemic Lupus Erythematosus internal organs. Renal involvement is thought to occur in about 60%
Systemic lupus erythematosus (SLE) is a relatively common disease of these patients, usually within 3 to 4 years of diagnosis. Manifestation
and has a predilection for women of childbearing age. Its coincidence may take one of three forms: sudden onset of malignant hypertension,
with pregnancy poses complex clinical problems because of the pro- rapidly progressive renal failure, or slowly increasing azotemia.110
found disturbance of the immunologic system, multiorgan involve- The combination of systemic sclerosis and pregnancy is unusual
ment, and complicated immunology of pregnancy itself.84 The outcome because the disease occurs most often in the fourth and fifth decades,
of pregnancy for women with SLE is variable and to some extent and affected patients are usually infertile. When it has its onset in
unpredictable, so careful monitoring, especially for those women with pregnancy, there is a greater tendency for deterioration. Patients with
lupus nephritis, is required (see Chapter 51). scleroderma and no evidence of renal involvement before conception
Decisions regarding the status of the disease and the importance of have developed severe kidney disease during gestation. There are
having a child to the patient and her partner should be made on an also instances in which pregnancy has been uneventful and successful,
individual basis. Most pregnancies succeed, especially when the mater- but marked reactivation occurred unexpectedly in the puerperium.
nal disease has been in complete clinical remission for 6 months before Most maternal deaths involve rapidly progressive scleroderma with
conception, even if there were marked pathologic changes in the origi- severe pulmonary complications, infections, hypertension, and renal
nal renal biopsy and heavy proteinuria in the early stages of the failure.
disease.106 Continued signs of disease activity or increasing renal dys- The extent of systemic involvement is probably more important
function reduces the likelihood of an uncomplicated pregnancy and than the duration of the disease, and limited, mild disease carries a
the clinical course thereafter. better prognosis. Sclerosis usually spares the abdominal wall skin, but
The effects of gestation on SLE activity and on the course of lupus there is one report of hydronephrosis, presumed to have been caused
nephritis have long been debated. Taking into account extrarenal man- by thickened skin and decreased abdominal wall compliance, in a twin
ifestations and renal changes, at least 50% of women show some pregnancy complicated by polyhydramnios.111
change in clinical status, often called a lupus flare.107 Some increments
in proteinuria or blood pressure may result from preeclampsia. Women
with lupus nephritis and renal insufficiency (serum creatinine level Wegener Granulomatosis
higher than 125 μmol/L or 1.4 mg/dL) that antedates pregnancy have Information on the outcome of pregnancy in women with Wegener
worse outcomes. granulomatosis is scarce. Proteinuria (with or without hypertension)
Lupus nephritis may sometimes become manifest during preg- is common, and reports have described complicated and uneventful
nancy, and when accompanied by hypertension and renal dysfunction, pregnancies.112 Experience with cyclophosphamide (Cytoxan) in preg-
it may be mistaken for preeclampsia. Some patients experience relapse, nancy is limited, and the risks to the embryo and fetus must be weighed
occasionally severely in the puerperium; therefore, some clinicians in relation to the course of the disease if such therapy were to be with-
prescribe or increase immunosuppression at this time.108 It is our prac- held from the mother.
tice to increase immunosuppression only if there are signs of increased
disease activity.
SLE serum contains an array of autoantibodies (i.e., lupus serum Previous Urinary Tract Surgery
factor) against nucleic acids, nucleoproteins, cell-surface antigens, and Permanent urinary diversion is still used in the management of patients
phospholipids. Antiphospholipid antibodies exert a complicated effect with congenital lower urinary tract defects, but its use for neurogenic
on the coagulation system.109 This led to the definition of a lupus bladder has declined since the introduction of self-catheterization.
anticoagulant, which is found in 5% to 10% of patients with SLE (see The most common complication of pregnancy is urinary infection.
Chapter 40). Because treatment with low-molecular-weight heparin Premature labor occurs in 20%, and the use of prophylactic antibiotics
and aspirin may lead to successful pregnancies, it is important to screen throughout pregnancy may reduce its incidence. Decline in renal func-
for lupus anticoagulant in women with SLE and especially in those tion may occur, invariably related to infection or intermittent obstruc-
with a history of recurrent intrauterine death or thrombotic episodes tion, or both. With an ileal conduit, elevation and compression by the
to identify this particular cohort. expanding uterus can cause outflow obstruction, whereas with a ure-
terosigmoid anastomosis, actual ureteral obstruction may occur. The
changes usually reverse after delivery.
Periarteritis Nodosa The mode of delivery is dictated by obstetric factors. Abnormal
In contrast to lupus nephritis, the outcome of pregnancy in women presentation accounts for a cesarean section rate of 25%. Vaginal deliv-
with renal involvement as a result of periarteritis nodosa is very poor, ery is safe, but because the continence of a ureterosigmoid anastomosis
largely because of the associated hypertension, which frequently is depends on an intact anal sphincter, this area must be protected with
malignant. Many cases in the literature have involved maternal demise. a mediolateral episiotomy.
However, this dismal prognosis is based primarily on selected anec- During the past decade, urinary tract reconstruction by means of
dotal studies, and a few successful pregnancies have been reported. augmentation cystoplasty, with or without artificial genitourinary
Still, until more data are available (perhaps through a registry), con- sphincter, has become more common. Deterioration of renal function
sideration of early therapeutic termination must be made in the best and urinary tract obstruction or infection can occur at any time in
interests of maternal health. pregnancy. Delivery by cesarean section is recommended for these

11. CHAPTER 44 Renal Disorders 915
gravidas because of the potential for disruption of the continence incidence of this HIV-associated nephropathy appears to be increas-
mechanism. ing, particularly in the African-American population and in cases
of intravenous drug abuse. Although few cases of this nephropathy
have been reported in pregnant women, with the rising incidence
Solitary Kidney of acquired immunodeficiency syndrome (AIDS), especially
Some patients have a congenital absence of one kidney or marked among black African women, this form of renal disease should
unilateral renal hypoplasia. Most, however, have had a previous be considered in HIV-infected patients presenting with severe
nephrectomy because of pyelonephritis (with abscess or hydronephro- proteinuria.
sis), unilateral tuberculosis, congenital abnormalities, or a tumor. It is
important to know the indication for and the time elapsed since the
nephrectomy. In patients with an infectious or a structural renal Factors Affecting Prognosis
problem, sequential pre-pregnancy investigation is needed to detect
any persistent infection. Effects of Specific Disorders on Fetal Outcome
It makes no difference whether the right or left kidney remains, as The problems associated with the specific disorders discussed in this
long as it is located in the normal anatomic position. If function is section are summarized in Table 44-4. In general, we suggest that pre-
normal and stable, women with this problem seem to tolerate preg- served renal function and the absence of hypertension before concep-
nancy well despite the superimposition of GFR increments on already tion predict successful fetal outcome and few maternal complications,
hyperfiltering nephrons. Single kidneys are most often associated with regardless of the nature of the disorder. These conclusions often are
the rare instances of acute renal failure as a result of obstruction during based on poorly controlled, retrospective data, underscoring the need
pregnancy. for registries and for prospectively acquired data; there is only one such
Ectopic kidneys (usually pelvic) are more vulnerable to infection study.70
and are associated with decreased fetal salvage, probably because of
associated malformations of the urogenital tract. If infection occurs in Effect of Pregnancy on Renal Disease/
a solitary kidney during pregnancy and does not quickly respond to Remote Prognosis
antibiotics, termination may have to be considered for preservation of Pregnancy does not adversely affect the natural history of the renal
renal function. lesion if kidney dysfunction is minimal and hypertension is absent at
conception, with the exception of certain collagen disorders. An impor-
tant factor in remote prognosis is the sclerotic effect that hyperfiltra-
Nephrotic Syndrome tion might already have had in the residual (intact) glomeruli of
The most common cause of nephrotic syndrome in late pregnancy is kidneys of patients with renal insufficiency. Further progressive loss
preeclampsia. Other causes include proliferative or membranoprolif- of renal function can ensue in pregnancy, but this is not the case
erative glomerulonephritis, lipid nephrosis, lupus nephritis, hereditary in animals when pregnancy is superimposed on experimental
nephritis, diabetic nephropathy, renal vein thrombosis, and amyloido- glomerulonephritis.115
sis. Some of these conditions do not respond to steroids and may even The superimposition of pregnancy hyperfiltration on the com-
be aggravated by them; this emphasizes the importance of a tissue pensatory changes already present in a single kidney may lessen the
diagnosis before steroid therapy is begun.113 lifespan of the kidney. The crux of this hypothesis is the implication
If renal function is adequate and hypertension is absent, there that increases in glomerular pressure or glomerular plasma flow
should be few complications during pregnancy and good fetal outcome. cause sclerosis within the glomerulus and that in pregnancy further
However, physiologic changes occurring during gestation may mimic physiologic hyperfiltration augments the damage. In health, it
aggravation or exacerbation of disease. Increments in renal hemody- seems unlikely that there are long-term renal sequelae.115 More human
namics and increases in renal vein pressure may enhance protein and animal research is needed because patients with renal disease
excretion during pregnancy. Serum albumin levels usually decrease can have unpredicted, accelerated, and irreversible renal decline
by 0.5 to 1.0 g/dL during normal pregnancy, and further decreases in pregnancy or immediately afterward, and the mechanisms are
due to nephrotic syndrome may enhance the tendency toward fluid unknown.
retention. Care must be taken with the use of diuretics to treat edema
because reduced intravascular volume may reduce uteroplacental
perfusion or aggravate the increased tendency to thrombotic
episodes. Hemodialysis Patients
and Pregnancy
Human Immunodeficiency Virus— It has been several decades since the first description of conception and
Associated Nephropathy successful delivery in a patient on chronic hemodialysis, and additional
During the past 25 years, there have been increasing numbers of case reports and registry data have been published since then.116-119 Any
reports about a nephrotic syndrome and severe renal impairment in optimism must be tempered by the thought that clinicians are reluc-
patients infected with the human immunodeficiency virus (HIV).114 tant to publish failures or disasters, and consequently, the true inci-
The condition is characterized by severe proteinuria, by bright dence of unsuccessful pregnancies in women on dialysis cannot be
echogenic kidneys, and often by rapid progression to end-stage determined. The high surgical abortion rate in these patients, although
renal disease. The distinctive features seen on histologic evaluation decreased from 40% in 1989 to 18% today, still indicates that those
of renal biopsy are a collapsing glomerulosclerosis, visceral epithelial who become pregnant do so accidentally, probably because they are
cell hypertrophy, and cystic tubular degenerative changes.114 The unaware that pregnancy is a possibility.

12. 916 CHAPTER 44 Renal Disorders
TABLE 44-4 CHRONIC RENAL DISEASE AND PREGNANCY
Renal Disease Effects
Chronic glomerulonephritis and Incidence of high blood pressure late in gestation is increased, but there usually is no adverse effect if
focal glomerular sclerosis (FGS) renal function is preserved and hypertension is absent before gestation. Some disagree, believing
coagulation changes in pregnancy exacerbate disease, especially immunoglobulin A (IgA)
nephropathy, membranoproliferative glomerulonephritis, and FGS.
IgA nephropathy Some cite risks of sudden escalating or uncontrolled hypertension and renal deterioration. Most find
good outcomes when renal function is preserved.
Chronic pyelonephritis (infectious Bacteriuria occurs in pregnancy and may lead to exacerbation.
tubulointerstitial disease)
Reflux nephropathy In the past, some emphasized risks of sudden escalating hypertension and worsening of renal
function. Consensus now is that results are satisfactory when preconception function is only mildly
affected and hypertension is absent. Vigilant screening for urinary tract infections is necessary.
Urolithiasis Ureteral dilatation and stasis do not seem to affect natural history, but infections can become more
frequent. Stents have been successfully placed, and sonographically controlled ureterostomy has
been performed during gestation.
Polycystic kidney disease Functional impairment and hypertension are usually minimal in childbearing years.
Diabetic nephropathy There are no adverse effects of the renal lesion. Frequencies of infections, edema, and preeclampsia
increase.
Systemic lupus erythematosus Prognosis is most favorable if disease is in remission 6 or more months before conception. Some
authorities increase steroid dosage in the immediate postpartum period.
Periarteritis nodosa Fetal prognosis is poor. Disease is associated with maternal death. Therapeutic abortion should be
considered.
Scleroderma For onset during pregnancy, there can be rapid overall deterioration. Reactivation of quiescent
scleroderma can occur during pregnancy and after delivery.
Previous urologic surgery Depending on the original reason for surgery, there may be other malformations of the urogenital tract.
Urinary tract infection is common during pregnancy, and renal function may undergo reversible
decrease. No significant obstructive problem, but cesarean section may be necessary in case of
abnormal presentation or to avoid disruption of the continence mechanism if artificial sphincters or
neourethras are present.
After nephrectomy, solitary and Pregnancy is well tolerated. Condition may be associated with other malformations of the urogenital
pelvic kidney tract. Dystocia rarely occurs with a pelvic kidney.
Counseling and Early TABLE 44-5 ESTIMATES FOR PREGNANCY
Pregnancy Assessment COMPLICATIONS AND OUTCOMES
Despite irregular or absent menstruation and impaired infertility, IN DIALYSIS PATIENTS
women on dialysis should use contraception if they wish to avoid
Complication or Outcome Incidence or Timing*
pregnancy.120 The introduction of recombinant human erythro-
poietin (rHuEPO) for the treatment of women with renal failure Polyhydramnios 40%
appears to be associated in some cases with return of normal Intrauterine growth restriction 90%
Preterm delivery 85%
menses (and ovulation), probably because of improved overall
Average gestational age at delivery 33 wk
health.121
Hypertension/preeclampsia 70%
There are substantial arguments against pregnancy, not least of (Severe) 15%
which are the risks to the patient (e.g., severe hypertension, cardiac Surviving infant
failure, maternal death) and the fact that even when therapeutic ter- Conceived on dialysis 50%
mination of pregnancy is excluded, there is at the very best only a 40% Conceived before dialysis 75%
to 50% likelihood of a successful outcome.122 If only data since the late
1990s are considered, fetal survival seems to be improving, although *Estimates are based on literature from 1992 to 2007, with all
pregnancies attaining at least 24 weeks’ gestation.
maternal risk remains formidable (Table 44-5).116 Data from references 2, 88, 121, 123-127, 163, 164.
Early diagnosis of pregnancy is difficult. A missed period is
usually ignored. The mistake the clinician may make is failure to
consider the possibility of pregnancy, and many of these patients have
Antenatal Strategy and
not been given contraception counseling. Resistance to rHuEPO or
progression of anemia (i.e., hematocrit decrease by 8% of pre- Decision Making
pregnancy levels) can be a useful clue to early diagnosis of pregnancy. For a successful outcome, scrupulous attention must be paid to blood
Urine pregnancy tests are unreliable, and definitive diagnosis and pressure control, fluid balance, increased hours of dialysis, and provi-
estimation of gestational age are best accomplished by sonar sion of good nutrition. Excellent publications should be consulted for
technology. more details.116,123-127