Chapter 56. Renal and Urinary Tract Disorders
Bs. Nguyễn Hồng Anh
Disorders o the kidneys and urinary tract are commonly
encountered in pregnancy. Some precede pregnancy—one
example is nephrolithiasis. Pregnancy-induced changes may
predispose to the development or worsening o urinary tract
disorders—an example is the markedly increased risk or pyelonephritis. Last, renal pathology unique to pregnancy, such as
preeclampsia, can develop. In one Australian study, kidney
disorders had an incidence o 0.3 percent in 407,580 births
(Fitzpatrick, 2019).
PREGNANCY-INDUCED URINARY
TRACT CHANGES
During normal pregnancy, signicant changes in both structure
and unction take place in the urinary tract (Chap. 4, p. 67)
Te kidneys become larger, and dilation o the renal calyces
and ureters can be striking. Some dilation develops beore
14 weeks and likely is due to progesterone-induced relaxation
o the muscularis. More marked dilation is apparent beginning
in midpregnancy and stems rom ureteral compression, especially on the right side. Vesicoureteral reux also occurs during pregnancy. Important consequences o these physiological
changes are an increased risk o upper urinary inection and
erroneous interpretation o studies.
Evidence o unctional renal hypertrophy becomes apparent
very soon ater conception. Glomeruli are larger, although cell
numbers are not greater (Strevens, 2003). Intrarenal vasodilation lowers resistance o both aerent and eerent arterioles,
and leads to higher eective renal plasma ow and glomerular
ltration (Helal, 2012; Hussein, 2014). By 12 weeks’ gestation,
the glomerular ltration rate (GFR) is already 20 percent above
nonpregnant values (Hladunewich, 2004). Ultimately, renal
plasma ow rises by 40 percent and GFR by 65 percent. Consequently, serum concentrations o creatinine and urea decline
substantively across pregnancy. Tus, values within a nonpregnant normal range may be abnormal or pregnancy (Appendix,
p. 1232). Other alterations include those related to acid–base
homeostasis and osmoregulation.
■ Assessment of Renal Function
During Pregnancy
Urinalysis results are essentially unchanged during normal pregnancy, except or occasional glucosuria. In nondiabetic gravidas,
glucosuria is thought to stem rom a pregnancy-related reduced
rate o renal tubular glucose reabsorption (Welsh, 1960). Tis
normal physiological change may add conusion and concerns
or a gestational diabetes mellitus (GDM) diagnosis. Indeed,
1+ or greater urine dipstick readings have been associated with
subsequent GDM diagnosis later in pregnancy. Despite this
association, urine dipstick testing alone shows poor sensitivity
to diagnose GDM (Buhlin, 2004; Olagbuji, 2015). For women
with glucosuria, no guidelines in the United States direct practice, but in the United Kingdom, early oral glucose testing is
considered or those with an isolated 2+ or repetitive 1+ urine
dipstick readings (National Institute or Health And Clinical
Excellence, 2015). Tis seems to be a reasonable approach.
Protein excretion is slightly elevated, but it seldom reaches
levels that are detected by usual screening methods. Higby and
colleagues (1994) reported 24-hour protein excretion in normal
pregnancy to be 115 mg, with a 95-percent condence level o
260 mg/d (Chap. 4, p. 68). Tis value did not signicantly di-
er by trimester. Albumin constitutes only a small part o total
protein excretion, and amounts range rom 5 to 30 mg/d. From
their review, Airoldi and Weinstein (2007) concluded that proteinuria must exceed 300 mg/d to be considered abnormal. Many
consider 500 mg/d to be important with gestational hypertension.
As an initial surrogate or 24-hour collections, quantication o
the urinary protein-to-creatinine ratio in a spot urine sample is
helpul in estimating a 24-hour protein excretion rate. Te ratio
is nearly the same numerically as the number o grams o protein
excreted in urine per day. Tis measurement is best obtained rom
a rst morning void. Surprisingly, women with lower urinary
tract inections do not have more proteinuria (Stephens, 2019).
Blood is another urinalysis marker. In one study, 3 percent
o 4307 nulliparas who were screened beore 20 weeks’ gestation had idiopathic hematuria, dened as 1+ or greater blood
on urine dipstick (Stehman-Breen, 2002). Tese women had a
twoold higher risk o developing preeclampsia. However, the
link between preeclampsia and hematuria has not been ound
by all (Brown, 2005; Shahriaki, 2016). In another study o
1000 women screened during pregnancy, Brown and coworkers
(2005) reported a 15-percent incidence o dipstick microscopic
hematuria. Most women had trace levels o hematuria, and the
alse-positive rate with this tool was 40 percent. Notably, other
elements such as vitamin C, povidone-iodine, myoglobin, ree
hemoglobin can produce alse-positive results. Tus, positive
dipstick results should prompt ormal urinalysis. Microscopic
hematuria is dened as >3 red blood cells (RBCs) per highpowered eld (HPF).
For veried asymptomatic microscopic hematuria, ew
guidelines direct the best evaluation. History and physical oten
point to benign causes. I not, initial exclusion o inection by
urinalysis or culture is reasonable. For early glomerular disease,
serum creatinine and blood urea nitrogen levels, a spot proteinto-creatinine ratio or 24-hour urine collection, and urinalysis
with examination o urine sediment can aid diagnosis. With this
last step, proteinuria, dysmorphic RBCs, and cellular casts are
characteristics. o help exclude neoplastic or stone disease, magnetic resonance urography (MRU) o the upper and lower urinary tract and cystoscopy is suitable in pregnancy (Davis, 2012).
However, the American College o Obstetricians and Gynecologists (2017) recommends against the last steps to exclude cancer or asymptomatic, low-risk, never-smoking women younger
than 50 years who have ≤25 RBCs seen per HPF.
I the serum creatinine level in pregnancy persistently
exceeds 0.9 mg/dL (75 µmol/L), intrinsic renal disease should
be suspected (Wiles, 2019a). In these cases, some determine the
creatinine clearance as an estimate o the GFR.
O imaging tools, sonography inorms on renal size, relative
consistency, and elements o obstruction. Full-sequence intravenous pyelography is not done routinely. However, the clinical
situation may warrant one-shot pyelography, in which contrast
medium injection is ollowed ater 30 minutes by one or two
abdominal radiographs (Chap. 49, p. 873). Magnetic resonance
(MR) imaging o renal masses provides excellent results due to
its excellent resolution at sot-tissue interaces (Putra, 2009).
Cystoscopy is perormed or the same indications as in the nonpregnant population. Ureteroscopy similarly may be indicated
and carries an approximate 5-percent complication rate during
stone removal during pregnancy (Johnson, 2012).
Although relatively sae during pregnancy, renal biopsy usually is postponed unless results may change therapy. From a
review o 243 biopsies in pregnant women, the incidence o
complications was 7 percent compared with 1 percent in postpartum women (Piccoli, 2013). Lindheimer and colleagues
(2013) recommend its consideration or those with rapid deterioration o renal unction o unclear etiology or with symptomatic nephrotic syndrome. We have ound biopsy helpul in
selected cases to direct management. Renal biopsy perormed in
normal pregnant volunteers showed that approximately 50 percent had slight to moderate glomerular endotheliosis (Strevens,
2003). In contrast, all 27 women with proteinuric hypertension
had moderate to severe endotheliosis.
■ Pregnancy After Unilateral Nephrectomy
Ater removal o one kidney, a remaining normal kidney provides augmented compensatory renal unction. With pregnancy,
this is urther amplied. Functional evaluation o the remaining
kidney is essential, even though most women have no diculty
in pregnancy. At minimum, the serum creatinine level is measured and a urine spot protein:creatinine ratio is determined.
No long-term permanent consequences accompany kidney
donation done beore pregnancy. However, the incidence o
subsequent preeclampsia is greater (Davis, 2019; Steele, 2019;
Vannevel, 2018).
URINARY TRACT INFECTIONS
Asymptomatic or covert bacteriuria is requent in pregnancy and
is an inection precursor. rue inections o the urinary tract
are the most prevalent bacterial inections during pregnancy.
Symptomatic inection includes cystitis, or it may involve the
renal calyces, pelvis, and parenchyma to cause pyelonephritis.
Organisms rom the normal perineal ora cause urinary
inections. Escherichia coli strains most commonly cause nonobstructive pyelonephritis. In approximately 90 percent o these
organisms, adhesins such as P- and S-mbriae are present. Tese
are cell-surace protein structures that enhance bacterial adherence to vaginal and uroepithelial cells and virulence (Hooton,
2012; Spurbeck, 2011). Maternal deaths have been attributed
to E coli bearing Dr+ and P adhesins (Sledzińska, 2011).
Urinary stasis, vesicoureteral reux, and diabetes mellitus
predispose to symptomatic upper urinary inections. Moreover,
data suggest that pregnant women have more severe sequelae
rom urosepsis. As one inuence, the helper cell (T1:T2)996 Medical and Surgical Complications
Section 12
ratio o normal pregnancy is reversed (Chap. 4, p. 61). Additionally, various perturbations o cytokine expression have been
reported (Chaemsaithong, 2013).
In the puerperium, several risk actors also predispose a
woman to urinary inections. Bladder sensitivity to intravesical uid tension is oten diminished as a consequence o labor
trauma or conduction analgesia (Chap. 36, p. 638). Also, the
sensation o bladder distention can be masked by discomort
rom an episiotomy, periurethral laceration, or vaginal wall
hematoma. Normal postpartum diuresis, while usually protective, may worsen bladder overdistention, and catheterization per-
ormed to relieve retention may lead to urinary inection.
■ Asymptomatic Bacteriuria
Tis reers to persistent, actively multiplying bacteria within the
urinary tract in asymptomatic women. It is dened as one or
more bacterial species that has a count ≥105 colony-orming
units/mL determined by urine culture o a voided specimen
(Inectious Disease Society o America, 2019). Its prevalence in
sexually active nonpregnant women is 2 to 6 percent ( Hooten,
2000; Nicolle, 2003). Te highest incidence is in AricanAmerican multiparas with sickle-cell trait, and the lowest
incidence is in afuent white women o low parity. Asymptomatic inection is also more common in women with diabetes
(Schneeberger, 2014). In most women, bacteriuria is recurrent
or persistent, and thus it requently is discovered during prenatal care. Te incidence during pregnancy is similar to that in
nonpregnant women and varies rom 2 to 7 percent (Nicolle,
2003).
Bacteriuria is typically already present at the time o the rst
prenatal visit. An initial positive urine culture result should
prompt treatment, ater which, ewer than 1 percent o women
develop a symptomatic UI (Whalley, 1967). It may be prudent to treat lower concentrations, because pyelonephritis
develops in some women with colony counts o only 20,000 to
50,000 organisms/mL (Lucas, 1993).
Significance
I asymptomatic bacteriuria (ASB) is not treated, approximately
25 percent o aected women will develop symptomatic inection during pregnancy. Eradication o bacteriuria with antimicrobial agents prevents most o these. Te American Academy
o Pediatrics and the American College o Obstetricians and
Gynecologists (2017), as well as the U.S. Preventive Services
ask Force (2019), recommend screening or bacteriuria at
the rst prenatal visit (Chap. 10, p. 181). Standard urine cultures may not be cost eective when the prevalence is low.
Instead, less expensive screening tests such as the leukocyte
esterase and nitrite dipstick are cost-eective (Chu, 2018).
At Parkland Hospital, culture screening is done because o a
5- to 8-percent prevalence o bacteriuria. Susceptibility determination is not necessary because initial treatment is empirical
(Hooton, 2012). Last, a special agar-coated dipstick culture
technique has excellent positive and negative predictive values
(Rogozińska, 2016).
Other than pyelonephritis prevention, it is unclear whether
ASB treatment provides other benets. In many studies, there
was no distinction rom symptomatic inection. For example, in
a cohort o 25,746 mother-newborn pairs, Schieve and coworkers (1994) reported UI to be associated with increased risks
or low-birthweight neonates, preterm delivery, pregnancyassociated hypertension, and anemia. Tese ndings vary rom
those o Gilstrap and colleagues (1981b) and Whalley (1967),
who studied asymptomatic inection. A Caliornia database
study reported 160,000 women with UIs were treated in the
emergency department or hospital (Baer, 2021). Tese presumed symptomatic inections were associated with a 1.4-old
higher preterm delivery rate in those <37 weeks.
Treatment
Bacteriuria responds to empirical treatment with any o several antimicrobial regimens listed in Table 56-1. E coli is the
most common species isolated in pregnant women (Le Blanc,
1964; Nicolle, 2003). Selection can be based on in vitro susceptibilities. However, in our extensive experience, empirical
oral treatment or 10 days with nitrourantoin macrocrystals,
100 mg at bedtime, is usually eective. Lumbiganon and associates (2009) reported satisactory results with a 7-day oral
course o nitrourantoin, 100 mg given twice daily. Singledose antimicrobial therapy also has been used with success or
bacteriuria. Te important caveat is that, regardless o regimen given, the recurrence rate approximates 30 percent. Tis
may indicate covert upper tract inection and the need or
longer therapy.
TABLE 56-1. Oral Antimicrobial Agents Used for
Treatment of Pregnant Women with
Asymptomatic Bacteriuria
Singledose treatment
Amoxicillin, 3 g
Ampicillin, 2 g
Cephalosporin, 2 g
Nitrofurantoin, 200 mg
Trimethoprim-sulfamethoxazole, 320/1600 mg
3day course
Amoxicillin, 500 mg three times daily
Ampicillin, 250 mg four times daily
Cephalosporin, 250 mg four times daily
Nitrofurantoin, 50 to 100 mg four times daily or 100 mg
twice daily
Trimethoprim-sulfamethoxazole, 160/800 mg two times
daily
Other
Nitrofurantoin, 100 mg four times daily for 10 days
Nitrofurantoin, 100 mg twice daily for 5 to 7 days
Nitrofurantoin, 100 mg at bedtime for 10 days
For treatment failures
Nitrofurantoin, 100 mg four times daily for 21 days
Suppression for bacterial persistence or recurrence
Nitrofurantoin, 100 mg at bedtime for remainder of
pregnancyRenal and Urinary Tract Disorders 997
CHAPTER 56
Periodic surveillance is necessary to prevent recurrent UIs
(Schneeberger, 2015). Te rst recurrence is considered a treatment ailure and extended therapy or 21 days is considered.
For women with persistent or requent ASB, suppressive therapy or the remainder o pregnancy can be given. We routinely
use nitrourantoin, 100 mg orally at bedtime. Its rare but serious side eects are pulmonary and hepatic toxicity.
■ Cystitis and Urethritis
According to the Centers or Disease Control and Prevention,
7.2 percent o pregnant women were treated as an outpatient
or a UI in 2014 (Ailes, 2018). Cystitis is characterized by
dysuria, urgency, and requency but causes ew associated systemic ndings. Pyuria and bacteriuria are usually ound. Microscopic hematuria is common, and occasionally gross hematuria
stems rom hemorrhagic cystitis. Although cystitis is usually
uncomplicated, the upper urinary tract may become involved
by ascending inection. Almost 40 percent o pregnant women
with acute pyelonephritis have preceding symptoms o lower
tract inection (Gilstrap, 1981a).
Women with cystitis respond readily to any o several regimens. Most o the three-day regimens listed in able 56-1 are
usually 90-percent eective. Single-dose therapy is less eective,
and i it is used, concomitant pyelonephritis must be con-
dently excluded.
Lower urinary tract symptoms with pyuria accompanied by
a sterile urine culture may be rom urethritis caused by Chlamydia trachomatis. Mucopurulent cervicitis usually coexists, and
azithromycin therapy is eective (Chap. 68, p. 1212).
■ Acute Pyelonephritis
Inection o the renal parenchyma is the most common serious nonobstetrical medical complication o pregnancy. One
study o the Nationwide Inpatient Sample ound that nearly
29,000 hospitalizations in 2006 were or acute pyelonephritis
in pregnancy (Jolley, 2012). Te highest rates were noted or
adolescents at 17.5 per 1000 and or Hispanic women at 10.1
per 1000. In another study o more than 70,000 pregnancies
in a managed care organization, 3.5 percent o antepartum
admissions were or urinary inections (Gazmararian, 2002).
Te seriousness is underscored by the observations o Snyder
and coworkers (2013) that pyelonephritis was the leading cause
o septic shock during pregnancy. Moreover, in a 2-year audit
o admissions to the Parkland Hospital Obstetrical Intermediate Care Unit, 12 percent o antepartum admissions were or
sepsis caused by pyelonephritis (Zeeman, 2003). O concern,
maternal urosepsis may be related to an increased incidence o
cerebral palsy in preterm newborns (Jacobsson, 2002). Fortunately, data do not suggest serious long-term maternal sequelae
(Raz, 2003).
Clinical Findings
Renal inection develops more requently in the second hal o
pregnancy, and nulliparity and young age are risk actors (Hill,
2005). Pyelonephritis is unilateral and right-sided in more than
hal o cases, and it is bilateral in a ourth. Its abrupt onset is
marked by ever, shaking chills, and aching pain in one or both
lumbar regions. Anorexia, nausea, and vomiting may worsen
dehydration. enderness usually can be elicited by percussion
in one or both costovertebral angles. Te urinary sediment
contains many leukocytes, requently in clumps, and numerous bacteria. Te dierential diagnosis includes, among others,
labor, chorioamnionitis, appendicitis, placental abruption, or
inarcted leiomyoma.
Bacteremia is demonstrated in 15 to 20 percent o these
women. E coli is isolated rom urine or blood in 70 to 80 percent
o inections, Klebsiella pneumoniae in 3 to 5 percent, Enterobacter or Proteus species in 3 to 5 percent, and gram-positive organisms, including group B Streptococcus and Staphylococcus aureus,
in up to 10 percent o cases (Hill, 2005; Wing, 2000). Evidence
o sepsis is common, and this is discussed in detail in Chapter
50 (p. 888).
During care, plasma creatinine is monitored, because
5 percent o pregnant women develop renal dysunction
despite aggressive uid resuscitation (Hill, 2005). Follow-up
studies have demonstrated that this endotoxin-induced damage is reversible in the long term (Whalley, 1975). In up to
10 percent o women, varying degrees o respiratory insu-
ciency, including rank pulmonary edema, may result rom
endotoxin-induced alveolar injury (Cunningham, 1987;
Sheeld, 2005; Snyder, 2013). In some cases, pulmonary
injury may be so severe that it causes acute respiratory distress
syndrome (ARDS).
Uterine activity rom endotoxins is common and is related
to ever severity. In a study by Millar and associates (2003),
women with pyelonephritis averaged 5 contractions per
hour at admission, and this declined to 2 per hour within
6 hours o intravenous uid and antimicrobial administration. β-agonist therapy or tocolysis raises the likelihood o
respiratory insuciency rom permeability edema because
o the sodium- and uid-retaining properties o those agents
(Chap. 50, p. 883). In one study, the incidence o pulmonary edema in women with pyelonephritis who were given
β-agonists was 8 percent—a ourold increase compared with
that expected (owers, 1991).
Endotoxin-induced hemolysis is common, and approximately
a third o patients with pyelonephritis develop anemia (Cox,
1991). With recovery, hemoglobin regeneration is normal
because acute inection does not aect erythropoietin production
(Cavenee, 1994).
Management
One scheme or management o acute pyelonephritis is shown
in Table 56-2. Although we obtain blood cultures when the
patient temperature exceeds 39°C, prospective trials show them
to be o limited clinical utility (Wing, 2000). Intravenous hydration to ensure adequate urinary output is the cornerstone o treatment. Antimicrobials also are begun promptly with the caution
that they may initially worsen endotoxemia rom bacterial lysis.
Ongoing surveillance or worsening o sepsis is monitored by
serial determinations o urinary output, blood pressure, pulse,
temperature, and oxygen saturation. High ever should be lowered with a cooling blanket and acetaminophen. Tis is especially important in early pregnancy because o possible teratogenic
eects o hyperthermia.998 Medical and Surgical Complications
Section 12
Antimicrobial therapy usually is empirical, and ampicillin plus gentamicin; ceazolin or cetriaxone; or an extendedspectrum antibiotic were all 95-percent eective in randomized
trials (Sanchez-Ramos, 1995; Wing, 1998, 2000). Fewer than
hal o E coli strains are sensitive to ampicillin in vitro, but
gentamicin plus ampicillin or plus a cephalosporin generally
have a synergistic eect and excellent activity (Johnson, 2018).
Serum creatinine levels are monitored i nephrotoxic drugs are
given. Initial treatment at Parkland Hospital is ampicillin plus
gentamicin. Some recommend suitable substitutes i bacterial
studies show in vitro resistance. With any o the regimens discussed, response is usually prompt, and 95 percent o women
are aebrile by 72 hours (Hill, 2005; Wing, 2000). Ater discharge, most recommend oral therapy to complete 10 to 14 days
(Hooton, 2012; Johnson, 2018).
Recurrent inection—either covert or symptomatic—is
common and develops in 30 to 40 percent o women ollowing
completion o pyelonephritis treatment. Unless other measures
are taken to ensure urine sterility, nitrourantoin, 100 mg orally
at bedtime given or the remainder o the pregnancy, reduces
bacteriuria recurrence.
Persistent Infection
Generally, stepwise deervescence o approximately 1°F per
day ollows intravenous hydration and antimicrobial therapy.
Upwards o 20 percent o women are ebrile or more than
4 days (Valent, 2017). With persistent spiking ever or lack
o clinical improvement by 48 to 72 hours, urinary tract
obstruction, calculi, or abscess is considered ( Johnson, 2018).
In these women, renal sonography is recommended to search
or these.
Obstruction maniests by abnormal ureteral or pyelocaliceal dilation. Nephrolithiasis, however, is not always seen in
a renal sonogram (Butler, 2000; Maikranz, 1987). I stones
are strongly suspected despite a nondiagnostic sonographic
examination, a plain abdominal radiograph will identiy
nearly 90 percent. Another option is the modied one-shot
intravenous pyelography (p. 995) (Butler, 2000). Last, persistent inection can be due to an intrarenal or perinephric
abscess or phlegmon (Cox, 1988; Ra, 2012). MR imaging
is preerred or abscess detection i renal sonography is nonconclusive (Rubilotta, 2014).
Obstruction relie is important, and we have ound that
percutaneous nephrostomy is preerable because the stents are
more easily replaced. Another method is cystoscopic placement
o a double-J ureteral stent. Tese stents are usually let in place
until ater delivery and oten become encrusted and need replacing (Lindquester, 2021). Last, in some women, surgical removal
o stones may be needed (p. 1000). Renal abscesses larger than
3 cm may necessitate percutaneous drainage or surgical treatment
(Coelho, 2007; Mandal, 2017; Siegel, 1996).
Outpatient Management of Pyelonephritis
Tis is an option or nonpregnant women with uncomplicated
pyelonephritis (Fox, 2017; Johnson, 2018). Wing and colleagues
(1999) described such management in 92 pregnant women who
were rst given in-hospital intramuscular cetriaxone, two 1-g
doses 24 hours apart. At this point, one third o the group was
considered suitable or outpatient therapy, and these women
were randomly assigned either to discharge and oral antimicrobials or to continued hospitalization with intravenous therapy. A
third o the outpatient management group was unable to adhere
to the treatment regimen and was admitted. Tese ndings suggest that outpatient management o pyelonephritis is applicable
only to very ew pregnant women.
■ Reflux Nephropathy
Tis reers to loss o nephron mass rom patchy interstitial scarring and tubular atrophy due to high-pressure reux o sterile
urine rom the bladder to the kidneys. In adults, long-term
complications include hypertension, which may be severe
i renal damage is demonstrable (Beck, 2018). Moreover,
reports describing 879 pregnancies in 432 women with reux
nephropathy indicate that impaired renal unction and bilateral
renal scarring were associated with higher rates o pregnancyassociated hypertensive disorders (Attini, 2018). Many also had
surgical correction o reux as children, and these women commonly have bacteriuria when pregnant (Mor, 2003). In other
women with reux nephropathy, no clear history implicates
recurrent cystitis, acute pyelonephritis, or obstructive disease
(Gebäck, 2016). Chronic renal disease and pregnancy outcome
is discussed urther later (p. 1003).
NEPHROLITHIASIS
Kidney stones develop in 9 percent o women during their lietime with an average age o onset in the third decade (Curhan,
2018). Calcium salts make up approximately 80 percent o
stones, and hyperparathyroidism should be excluded. Calcium oxalate stones are most common in young nonpregnant
women, but in pregnancy most stones—65 to 75 percent—are
calcium phosphate or hydroxyapatite (an, 2013).
TABLE 56-2. Management of the Pregnant Woman with
Acute Pyelonephritis
Hospitalize patient
Obtain urine and blood cultures
Evaluate hemogram, serum creatinine, and electrolytes
Monitor vital signs frequently, including urinary output—
consider indwelling catheter
Establish urinary output ≥50 mL/h with IV crystalloid
solution
Administer IV antimicrobial therapy (see text)
Obtain chest radiograph if there is dyspnea or tachypnea
Repeat hematology and chemistry studies in 48 h
Change to oral antimicrobials when afebrile
Discharge when afebrile 24 h, consider antimicrobial
therapy for 7-10 d
Repeat urine culture 1–2 wks after antimicrobial therapy
completed
IV = intravenous.
From Lucas, 1994; Sheffield, 2005.Renal and Urinary Tract Disorders 999
CHAPTER 56
Nephrolithiasis is more common in women with prior pregnancies than in nulligravidas. Normal physiological changes o
the urinary system may promote stone ormation, and elevation o urinary pH reduces calcium phosphate solubility (Reinstatler, 2017). More than hal o patients who have a stone
typically orm another stone within 10 years.
Contrary to past teachings, a low-calcium diet promotes
stone ormation. Current recommendations to prevent recurrences include hydration and a diet low in sodium and protein
(Curhan, 2018). Tiazide diuretics also diminish stone ormation. In general, obstruction, inection, intractable pain, and
heavy bleeding are indications or stone removal. Extraction by
a exible basket via cystoscopy, although used less oten than in
the past, is still a reasonable consideration or pregnant women.
In nonpregnant patients, stone destruction by lithotripsy is pre-
erred to surgical therapy in most cases. Limited inormation
guides the use o lithotripsy during pregnancy, and it is not
generally recommended.
■ Stone Disease During Pregnancy
Te reported incidence o stone disease complicating pregnancy
varies widely. At the low end, Butler and coworkers (2000) ound
an incidence o 0.3 admissions per 1000 pregnancies in more
than 186,000 deliveries at Parkland Hospital. In an Israeli study,
the incidence in nearly 220,000 pregnancies was 0.8 per 1000
(Rosenberg, 2011). Most stone episodes are diagnosed in the
second and third trimesters o pregnancy (Dai, 2021). Bladder
stones are rare, but recurrent inection and labor obstructed by
stones have been reported (Ait Benkaddour, 2006; Ruan, 2011).
Data are conicting whether women with kidney stones
have an increased risk or adverse pregnancy outcomes. Swartz
and colleagues (2007) reported a preterm delivery rate o
10.6 percent in women with nephrolithiasis compared with
6.4 percent in normal controls. A nationwide case-control
study rom aiwan also reported 20- to 40-percent increases in
low-birthweight newborns and preterm births (Chung, 2013).
o the contrary, a case-control study rom Hungary reported
that pregnancy outcomes, including preterm delivery, were
similar in women with and without stone disease (Banhidy,
2007). Comparable conclusions were drawn rom the Israeli
study noted earlier (Rosenberg, 2011). Women who have
ormed stones prior to pregnancy have a higher incidence o
gestational diabetes and preeclampsia (angren, 2018).
Diagnosis
More than 90 percent o pregnant women with nephrolithiasis present with pain. However, some evidence suggests that
pregnant women may have ewer symptoms with stone passage
because o normal urinary tract dilation (an, 2013). Gross
hematuria is less common than in nonpregnant women and has
an incidence o 2 to 23 percent (Butler, 2000; Lewis, 2003).
Sonography is the rst-line study to visualize stones, but as
discussed above, many are undetected (McAleer, 2004). Abnormal urinary tract dilation or absent ureteral “jets” o urine into
the bladder are indirect indicators o urolithiasis (Fig. 56-1). I
abnormal dilation is seen but no stone is visualized, one-shot
pyelography may be useul.
Helical computed tomography (C) scanning is preerred
imaging or nonpregnant individuals. In pregnancy, MR imaging is the second-line test ollowing a nondiagnostic sonographic
evaluation (Masselli, 2013). However, i C imaging is needed,
White and colleagues (2007) recommend unenhanced helical
C and cite an average etal radiation dose to be 7 mGy.
Management
reatment depends on symptoms and gestational age (Semins,
2013). Intravenous hydration and analgesics are given. Patients
strain collected urine to identiy passed stones. In hal o
women with symptomatic stones, inection will be identied,
and this is treated vigorously. Although calculi inrequently
cause symptomatic obstruction during pregnancy, persistent
pyelonephritis should prompt a search or obstruction due to
nephrolithiasis.
Approximately 75 percent o symptomatic women will
improve with conservative therapy, and the stone usually
passes spontaneously (an, 2013). Others require an invasive
procedure such as ureteral stenting, ureteroscopy, percutaneous
nephrostomy, transureteral laser lithotripsy, or basket extraction (Butler, 2000; Hosseini, 2017). Watterson and coworkers
A B C
FIGURE 56-1 A. Sonographic image of the right upper quadrant demonstrates severe hydronephrosis and thinned echogenic renal parenchyma. B. Application of color Doppler during sonography of the bladder reveals a urine jet (red streak) from the left ureteral orifice. No flow was
noted from the right orifice during observation. C. Sagittal CT image shows an obstructing stone in the mid right ureter (arrow) and hydroureteronephrosis (arrow head).1000 Medical and Surgical Complications
Section 12
(2002) described successul transureteral holmium:YAG laser
lithotripsy in nine o 10 women. Ultimately, less than 2 percent
o symptomatic pregnant women require surgical exploration
ollowing one o the procedures listed above (Swartz, 2007).
Te need or uoroscopy limits the utility o percutaneous
nephrolithotomy. Extracorporeal shock-wave lithotripsy is contraindicated in pregnancy.
PREGNANCY AFTER RENAL
TRANSPLANTATION
In 2020, more than 100,000 registrants were waiting or renal
transplantations through the Organ Procurement and ransplantation Network—OPN (2020). Te 1-year grat survival
rate is 95 percent or those rom living donors and is 90 percent
rom deceased donors. Survival rates approximately doubled in
the 1990s, due in large part to the introduction o cyclosporine and muromonab-CD3 (Orthoclone OK3) to prevent
and treat organ rejection. Te latter is a monoclonal antibody
against the CD3 receptor o cells. Since then, mycophenolate moetil and tacrolimus have urther reduced acute rejection
episodes. However, the ormer is teratogenic (Briggs, 2017). In
the report rom the National ransplant Pregnancy Registry,
23 percent o etuses exposed to mycophenolate had birth deects
(Coscia, 2010). Importantly, resumption o renal unction ater
transplantation promptly restores ertility in reproductive-aged
women (Yaprak, 2019). Tus, these women should be counseled to use contraception, especially those treated with mycophenolate. In one study, more than hal o transplant recipients
reported that they were not counseled regarding contraception
(French, 2013).
■ Pregnancy Outcomes
Women with solid organ transplant have higher severe maternal
morbidity rates (Sabr, 2019). Deshpande and associates (2011)
reviewed the outcomes o more than 4700 pregnancies in renal
transplant recipients. Approximately 70 percent o pregnancies resulted in a live birth. However, rates o preeclampsia,
gestational diabetes, and preterm delivery were substantially
greater. Similar outcomes were described or the Australian
and New Zealand ransplant Registry (Wyld, 2013). In the
United Kingdom, Bramham and colleagues (2013) identied
a live-birth rate that exceeded 90 percent in renal transplant
recipients. Hal were delivered beore 37 weeks’ gestation, but
only 9 percent beore 32 weeks. Low birthweight complicated
hal o pregnancies, and growth restriction complicated 25 percent. Notably, the incidence o etal malormations was not
increased, except in those who took mycophenolate moetil.
Te incidence o preeclampsia is high in all transplant recipients. In the UK National Cohort Study reported by Bramham
and associates (2013), the incidence o preeclampsia was 22 percent. From their review, Josephson and McKay (2011) cite an
incidence o one third o pregnancies but question the validity
o this requency. Importantly, in some cases, rejection is di-
cult to distinguish rom preeclampsia. Tat said, the incidence
o rejection episodes approximates only 2 percent (Bramham,
2013). Viral inections—especially polyomavirus hominis 1,
also called BK virus—are requent. In addition, gestational
diabetes is ound in approximately 5 percent. Both are likely
related to immunosuppression therapy. Similar outcomes have
been reported by several other investigators (Al Duraihimh,
2008; Cruz Lemini, 2007; Ghaari, 2008).
Te Italian Society o Nephrology recommends that women
who have undergone transplantation satisy several requisites
beore attempting pregnancy (Cabiddu, 2018). First, women
should be in good general health or at least 1 to 2 years ater
transplantation. Second, renal unction should be stable.
Parameters include a GFR ≥60 mL/min, serum creatinine level
<2 mg/dL, and proteinuria <500 mg/d. Tird, there should
be no recent evidence or grat rejection and no treatment with
teratogenic drugs. Last, hypertension should be absent or well
controlled.
Cyclosporine and tacrolimus are given routinely to renal
transplantation recipients. Coincident with expected pregnancyrelated intravascular volume expansion, cyclosporine blood
levels decline during pregnancy. However, this was not reported
to be associated with rejection episodes (Tomas, 1997). Unortunately, these agents are nephrotoxic and may also cause renal
hypertension. In act, they likely contribute substantively to the
chronic renal disease that develops in 10 to 20 percent o patients
with nonrenal solid organ transplantation (Goes, 2007).
Concern persists regarding the possible late eects in o-
spring subjected to immunosuppressive therapy in utero. Tese
include malignancy, germ cell dysunction, and malormations
in the children o the ospring. In addition, cyclosporine is
secreted in breast milk (Moretti, 2003). In two small studies,
these children had normal neurological and intellectual unction
(Morales-Buenrostro, 2019; Schreiber-Zamora, 2019).
Last, pregnancy-induced renal hyperltration theoretically
may impair long-term grat survival. However, Sturgiss and
Davison (1995) ound no evidence or this in one study o 34
allograt recipients ollowed or a mean o 15 years.
■ Management
Close surveillance is necessary. Covert bacteriuria is treated, and
i it is recurrent, suppressive treatment is given or the remainder o the pregnancy. Serial hepatic enzyme concentrations and
blood counts are monitored or toxic eects o azathioprine
and cyclosporine. Some recommend measurement o serum
cyclosporine levels. Gestational diabetes is more common i
corticosteroids are taken, and in these cases overt diabetes must
be excluded with glucose tolerance testing done at the initiation
o prenatal care. Surveillance or opportunistic inections rom
herpesvirus, cytomegalovirus, and toxoplasmosis is important
because these inections are common. Some recommend surveillance or BK virus in women known to be inected, however, diagnosis and treatment are problematic.
Renal unction is monitored, and the GFR usually increases
20 to 25 percent. I a signicant rise in the serum creatinine level
is detected, its cause must be determined. Possibilities include
acute rejection, cyclosporine toxicity, preeclampsia, inection,
and urinary tract obstruction. Evidence o pyelonephritis or
grat rejection should prompt admission or aggressive management. Imaging studies and kidney biopsy may be indicated.Renal and Urinary Tract Disorders 1001
CHAPTER 56
Te woman is careully monitored or development or worsening o underlying hypertension, and especially o superimposed
preeclampsia. Management o hypertension during pregnancy is
the same as or patients without an organ transplant (Chap. 53,
p. 950).
Vigilant etal surveillance is indicated because o the higher
incidences o etal-growth restriction and preterm delivery.
Although cesarean delivery is reserved or obstetrical indications, occasionally the transplanted kidney obstructs labor, and
the overall cesarean delivery rate approaches 80 percent (Bramham, 2013; Madej, 2018; Rocha, 2013).
POLYCYSTIC KIDNEY DISEASE
Tis usually autosomally dominant systemic disease primarily
aects the kidneys. Its basic pathophysiology is a ciliopathy that
aects renal tubules, although only approximately 5 percent
develop cysts (Zhou, 2018). Te incidence is about 1 in 1000
births and it causes approximately 5 to 10 percent o end-stage
renal disease in the United States. Although genetically heterogeneous, almost 85 percent o cases are due to PKD1 gene
mutations on chromosome 16, and the other 15 percent to
PKD2 mutations on chromosome 4. Prenatal diagnosis is available i the mutation has been identied in a amily member or
i linkage has been established in the amily. Preimplantation
genetic screening reduces the risk o aected etuses to 1 to
2 percent (Murphy, 2018).
Renal complications more commonly aect men than
women, and symptoms usually appear in the third or ourth
decade. Flank pain, hematuria, proteinuria, abdominal masses,
and associated calculi and inection are requent ndings.
Hypertension develops in 75 percent, and progression to renal
ailure is a major problem. Superimposed acute renal ailure also
may develop rom inection or obstruction rom ureteral angulation. Specically, renal cyst may displace and create angles along
the normal ureteral course.
Other organs are commonly involved. Asymptomatic hepatic
cysts coexist in a third o patients with polycystic kidneys.
Hepatic involvement is more common and more aggressive
in women than in men. Approximately 10 percent o patients
with polycystic kidney disease die rom rupture o an associated
intracranial berry aneurysm. Up to a ourth o patients have
cardiac valvular lesions, which include mitral valve prolapse and
mitral, aortic, and tricuspid valvular incompetence.
■ Pregnancy Outcomes
Te prognosis or pregnancy in women with polycystic kidney
disease depends on the degree o associated hypertension and
renal insuciency. Urinary inections are common. Chapman
and coworkers (1994) compared pregnancy outcomes in 235
aected women who had 605 pregnancies with those o 108
unaected amily members who had 244 pregnancies. Composite perinatal complication rates were similar—33 versus 26
percent—but hypertension, including preeclampsia, was more
common in women with polycystic kidneys. Pregnancy does
not seem to accelerate the natural disease course (Lindheimer,
2007).
GLOMERULAR DISEASES
Te glomerulus and its capillaries are subject to numerous conditions and agents that can lead to acute and chronic diseases.
Glomerular damage can be caused by toxins or inections or
rom systemic disorders such as hypertension or diabetes. It
may also be idiopathic. When there is capillary inammation,
the process is termed glomerulonephritis, and in many o these
cases, an autoimmune process is involved. Glomerular disease
or glomerulonephritis may result rom a single stimulus such as
that ollowing group A streptococcal inections. It may also be
a maniestation o a multisystem disease such as systemic lupus
erythematosus or diabetes (Blom, 2017).
Persistent glomerulonephritis eventually leads to decline
o renal unction. Progression is variable and oten does not
become apparent until chronic renal insuciency is diagnosed.
Lewis and Neilsen (2018) group glomerular injuries into six
syndromes based on clinical patterns (Table 56-3). Some
underlying disorders—examples include inections, vasculitides, and diabetes—can result in one clinical pattern in dierent individuals. Last, disorders within each o these categories
TABLE 56-3. Patterns of Clinical Glomerulonephritis
Acute nephritic syndromes: poststreptococcal, infective endocarditis, SLE, antiglomerular basement membrane
disease, IgA nephropathy, ANCA vasculitis, Henoch-Schönlein purpura, cryoglobulinemia, membranoproliferative and
mesangioproliferative glomerulonephritis
Pulmonaryrenal syndromes: Goodpasture, ANCA vasculitis, Henoch-Schönlein purpura, cryoglobulinemia
Nephrotic syndromes: minimal change disease, focal segmental glomerulosclerosis, membranous glomerulonephritis,
diabetes, amyloidosis, others
Basement membrane syndromes: antiglomerular basement membrane disease, others
Glomerular vascular syndromes: atherosclerosis, chronic hypertension, sickle-cell disease, thrombotic microangiopathies,
antiphospholipid antibody syndrome, ANCA vasculitis, others
Infectious disease–associated syndromes: poststreptococcal, infective endocarditis, HIV, HBV, HCV, syphilis, others
ANCA = antineutrophilic cytoplasmic antibodies; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IgA = immunoglobulin A; SLE = systemic lupus erythematosus.1002 Medical and Surgical Complications
Section 12
may be seen in young women, and thus, these may already be
established beore pregnancy or may rst maniest then.
As with any renal disorder, goals to achieve optimal pregnancy outcomes aim to stabilize rapid disease progression, minimize proteinuria with use o appropriate immunosuppressive
agents, control hypertension, and delay pregnancy until these
are achieved.
■ Acute Nephritic Syndromes
Acute glomerulonephritis may result rom any o several causes
(see able 56-3). Te clinical presentation usually includes hypertension, hematuria, red-cell casts, pyuria, and proteinuria. Varying
degrees o renal insuciency and salt and water retention result in
edema, hypertension, and circulatory congestion (Lewis, 2018).
Te prognosis and treatment o nephritic syndromes depends
on their etiology. Some recede spontaneously or with treatment.
However, in some patients, rapidly progressive glomerulonephritis
leads to end-stage renal ailure. In others, chronic glomerulonephritis
develops and maniests as slowly progressive renal disease.
Te prototype is acute poststreptococcal glomerulonephritis,
which is historically interesting because it was conused with
eclampsia until the mid-1800s. Immunoglobulin A (IgA) nephropathy, also known as Berger disease, is the most common orm
o acute glomerulonephritis worldwide (Blom, 2017). Te isolated orm o IgA nephropathy occurs sporadically, and it may
be related to Henoch-Schönlein purpura as the systemic orm.
Another isolated nephritis type may be due to anti– glomerular
basement membrane antibodies, which are typically IgG. Tese
IgG antibodies may also involve the lungs to maniest as a
pulmonary-renal syndrome with alveolar hemorrhage, which is
termed Goodpasture syndrome.
Pregnancy
Acute nephritic syndromes during pregnancy can be dicult to
dierentiate rom severe preeclampsia. One example is systemic
lupus erythematosus with a are during the second hal o
pregnancy (Zhao, 2013). In some cases, renal biopsy may
be necessary to determine etiology and direct management
( Lindheimer, 2013; Ramin, 2006). Tis is discussed urther in
Chapter 62 (p. 1112).
Whatever the underlying etiology, glomerular diseases have
proound eects on pregnancy outcome. In an older study,
Packham and coworkers (1989) described 395 pregnancies in
238 women with primary glomerulonephritis diagnosed beore
pregnancy. Te most common lesions identied by biopsy were
membranous glomerulonephritis, IgA glomerulonephritis, and
diuse mesangial glomerulonephritis. Although most o these
women had normal renal unction, hal developed hypertension, a ourth was delivered preterm, and the perinatal mortality
rate ater 28 weeks’ gestation was 80 per 1000. As expected, the
worst perinatal outcomes were in women with impaired renal
unction, early or severe hypertension, and nephrotic-range
proteinuria. O’Shaughnessy and colleagues (2017) conrmed
these ndings. In 48 pregnancies complicated by glomerulonephritis, a third developed preeclampsia, 39 percent had a doubling o protein excretion, and 27 percent had a ≥50-percent
rise in serum creatinine levels. Hal o the pregnancies ended in
preterm birth and 13 percent in perinatal death.
Similar outcomes have been reported or pregnancies in
women with IgA nephropathy. From one review o 376 pregnancies, investigators reported a perinatal mortality rate o 12-percent;
preterm delivery, 9 percent; low birthweight, 10 percent; and
preeclampsia, 7 percent (Liu, 2016). Progression o renal insu-
ciency during pregnancy is controversial. From their reports,
Su and coworkers (2017), but not Wang and colleagues (2019),
ound that women with IgA nephropathy had renal insuciency
progression during pregnancy.
■ Nephrotic Syndromes
Heavy proteinuria is the hallmark of the nephrotic syndromes. Several primary and secondary kidney disorders cause immunological- or toxic-mediated injury and glomerular capillary-wall breakdown that allows excessive filtration of plasma proteins.
In addition to heavy urine protein excretion, the syndrome is characterized by hypoalbuminemia, hypercholesterolemia, and edema. Hypertension is frequently comorbid. This, coupled with albumin nephrotoxicity, contributes to eventual renal insufficiency.
Some of the more common causes of the nephrotic syndrome are listed in Table 56-4. Treatment depends on etiology, and renal biopsy will disclose microscopic abnormalities that may help direct care. Edema is problematic, especially during pregnancy. Normal amounts of dietary protein of high biological value are encouraged, and this practice contrasts with high-protein diets, which increase proteinuria. The incidence of thromboembolism is greater and varies with the severity of hypertension, proteinuria, and renal insufficiency (Spotti, 2019).
Renal vein thrombosis is particularly worrisome, although both arterial and venous thromboses may develop. Explanations for this risk are platelet hyperactivity, urinary loss of antithrombotic factors, and increased production of prothrombotic factors by the liver (Mirrakhimov, 2014). Some recommend that TABLE 56-4. Causes of the Nephrotic Syndrome in Adults Focal segmental glomerulosclerosis (FSGS) (35%): viruses, hypertension, reflux nephropathy, sickle-cell disease
Membranous glomerulonephritis (∼20%): idiopathic (most cases), malignancy, infection, connective tissue diseases Minimal change disease (MCD) (10–15%): primary idiopathic (most cases), drug-induced (NSAIDs), allergies, viral infections Diabetic nephropathy: most common cause of ESRD
Glomerular deposition diseases: light-chain, amyloidosis
ESRD = end-stage renal disease; NSAIDs = nonsteroidal antiinflammatory drugs. women with a serum albumin <2 g/dL or 24-hour urinary protein excretion >3.5 g should be given thromboprophylaxis throughout pregnancy (Blom, 2017). Some cases of nephrosis from primary glomerular disease respond to glucocorticosteroids and other immunosuppressants or cytotoxic drug therapy.
In most cases caused by infection or drugs, proteinuria recedes once the underlying cause is corrected.
Pregnancy
Maternal and perinatal outcomes in women with a nephrotic syndrome depend on its underlying cause and severity. Whenever possible, these should be ascertained, and renal biopsy may be indicated to determine if there is a treatable etiology. Half of women with nephrotic-range proteinuria will have higher daily protein excretion as pregnancy progresses (Packham, 1989). In women with nephrosis cared for at Parkland Hospital, we reported that two thirds had protein excretion that exceeded 3 g/d (Stettler, 1992). At the same time, however, if these women had only mild degrees of renal dysfunction, they displayed a normally augmented GFR across pregnancy (Cunningham, 1990).
Management of edema during pregnancy can be particularly challenging, as it is intensified by normally rising hydrostatic pressure in the lower extremities. In some women, massive vulvar edema may develop in those with comorbid conditions such as diabetes, syphilis, preeclampsia, and others (Fig. 56-2) (Jakobi, 1995). Another major problem is that up to half of these women with nephrosis have chronic hypertension that may require treatment (Chap. 53, p. 950). In these, as well as in previously normotensive women, preeclampsia is common and often develops early in pregnancy (Morgan, 2016).
Most women with a nephrotic syndrome who do not have severe hypertension or renal insufficiency will have successful pregnancy outcomes. Conversely, if there is renal insufficiency, moderate to severe hypertension, or both, the prognosis is much worse. Our experiences caring for such women with 65 pregnancies at Parkland Hospital showed that complications are frequent (Stettler, 1992). Protein excretion during pregnancy averaged 4 g/d, and a third of the women had classic nephrotic syndrome.
Some degree of renal insufficiency was seen in 75 percent, chronic hypertension in 40 percent, and persistent anemia in 25 percent. Importantly, preeclampsia developed in 60 percent, and 45 percent had preterm deliveries. Even so, after excluding abortions, 53 of 57 neonates were born alive. De Castro and associates (2017) reported similar results from 26 pregnancies complicated by a mean protein excretion of 8 g/d.
Long-Term Outcomes
Women identified to have nephrotic syndromes either before or during pregnancy are at risk for serious long-term adverse outcomes. Of the women cared for at Parkland Hospital, at least 20 percent of women followed for 10 years progressed to end-stage renal failure (Stettler, 1992). Similarly, Chen and associates (2001) reported short-term outcomes in 15 women with nephrotic syndromes. By 2 years, three of these women had died, three had developed chronic renal failure, and two had progressed to end-stage renal disease. Women with serum creatinine levels >1.4 mg/dL and 24-hour protein excretion >1 g/d have the shortest renal survival times following pregnancy (Imbasciati, 2007)
FIGURE 56-2 Massive vulvar edema in a pregnant woman with marked proteinuria due to preeclampsia
CHRONIC KIDNEY DISEASE
Tis describes a pathophysiological process that can progress
to end-stage renal disease. Te National Kidney Foundation
(2019) describes six stages o chronic kidney disease (CKD)
dened by decreasing GFR. It progresses rom stage 0, in which
GFR is ≥90 mL/min/1.73 m2, to stage 5, in which GFR is
<15 mL/min/1.73 m2.
Several diseases result in progressively declining renal unction, including the glomerular diseases discussed earlier. Tose
that most commonly lead to end-stage disease requiring dialysis
and kidney transplantation include diabetes mellitus, chronic
hypertension, glomerulonephritis, and polycystic kidney disease
(Bargman, 2018).
Most reproductive-aged women with these just-mentioned diseases have varying degrees o renal insuciency, proteinuria, or
both. o counsel regarding ertility and pregnancy outcome, the
degree o renal unctional impairment and o associated hypertension are assessed. In general, successul pregnancy outcome may be
more related to these two actors than to the specic underlying
renal disorder. An overall prognosis can be estimated by considering women with CKD in arbitrary categories o renal unction
(Davison, 2011). Tese include normal or mild impairment—
dened as a serum creatinine <1.5 mg/dL; moderate impairment—dened as a serum creatinine 1.5 to 3.0 mg/dL; and severe
renal insuciency—dened as a serum creatinine >3.0 mg/dL.
Some recommend using these older categories, although others
suggest adopting the classication o the National Kidney Foundation described above (Davison, 2011; Piccoli, 2010, 2011). Tus,
obstetricians must be amiliar with both.
■ Pregnancy and Chronic Kidney Disease
Te severity o renal insuciency, along with any underlying
hypertension, strongly inuences pregnancy outcome. Additionally, comorbidities secondary to a systemic disorder—or
FIGURE 56-2 Massive vulvar edema in a pregnant woman with
marked proteinuria due to preeclampsia.1004 Medical and Surgical Complications
Section 12
example, diabetes or systemic lupus erythematosus—portend
a worse prognosis (Blom, 2017). For all women with CKD,
the incidences o hypertension and preeclampsia, preterm and
growth-restricted neonates, and other problems are high. Lowdose aspirin starting at 12 to 28 weeks is recommended to help
lower preeclampsia rates (Chap. 41, p. 705).
Loss o renal tissue is associated with compensatory intrarenal vasodilation and hypertrophy o the surviving nephrons.
Te resultant hyperperusion and hyperltration eventually
damage surviving nephrons to cause nephrosclerosis and worsening renal unction. With mild renal insuciency, pregnancy
causes greater augmentation o renal plasma ow and GFR
(Helal, 2012). With progressively worsening renal unction,
renal plasma ow is augmented little, i any. In one study, only
hal o women with moderate renal insuciency demonstrated
pregnancy-augmented glomerular ltration, and women with
severe disease had no increase (Cunningham, 1990).
Importantly, chronic renal insuciency also curtails normal
pregnancy-induced hypervolemia. Blood volume expansion
during pregnancy is related to disease severity and correlates
inversely with serum creatinine concentration. As shown in
Figure 56-3, women with mild to moderate renal dysunction
have blood volume expansion that averages 55 percent above
nonpregnant volumes. However, with severe renal insu-
ciency, volume expansion averages only 25 percent, which is
similar to that seen with hemoconcentration rom eclampsia. In
addition, these women have variable degrees o chronic anemia
due to intrinsic renal disease. Tus, they are at risk or hypovolemia and acute blood loss anemia with even normal blood
loss at delivery.
Renal Disease with Preserved Function
In some women, although glomerular disease has not yet caused
renal insuciency, incidences o pregnancy complications
are still increased. As shown in Table 56-5, these problems
are less requent than in cohorts o women with moderate and
severe renal insuciency. wo older studies illustrate this. In
one, Surian and colleagues (1984) described outcomes o 123
pregnancies in women with biopsy-proven glomerular disease.
Although only a ew o these women had renal dysunction,
40 percent developed obstetrical or renal complications. In
another study o 395 pregnancies in women with preexisting
glomerulonephritis and minimal renal insuciency, impaired
renal unction developed in 15 percent o these women during pregnancy, and 60 percent had worsening proteinuria
(Packham, 1989). Only 12 percent had antecedent chronic
hypertension, however, more than hal o the pregnancies were
complicated by hypertension. Te perinatal mortality rate was
140 per 1000, and even without early-onset or severe hypertension or nephrotic-range proteinuria, the rate was 50 per 1000.
Importantly, in 5 percent o these women, worsening renal
unction was permanent.
Chronic Renal Insufficiency
As noted, pregnancy complication rates are higher in women
with CKD and renal insuciency compared with women who
have preserved renal unction. Furthermore, adverse outcomes
are generally directly related to the degree o renal impairment.
O the more recent reports shown in able 56-5, outcomes
o women with moderate or severe renal insuciency are usually not separated. A systematic review o 1514 pregnancies
in women with CKD described increased odds ratios o preeclampsia, 10.4; preterm delivery, 6.3; etal-growth restriction,
4.9; and cesarean delivery, 2.7 (Zhang, 2015).
Other investigators have described pregnancies complicated
by moderate or severe renal insuciency (Cunningham, 1990;
0
Normal
pregnancy
Blood volume expansion
(percent above nonpregnant volume)
Eclampsia Mildmoderate
CRI
Severe
CRI
25
50
75
FIGURE 56-3 Blood volume expansion in 44 normally pregnant
women at term compared with 29 who had eclampsia; 10 with
moderate chronic renal insufficiency (CRI)—serum creatinine 1.5 to
2.9 mg/dL; and four with severe CRI—serum creatinine ≥3.0 mg/dL.
(Data from Cunningham, 1990; Zeeman, 2009.)
TABLE 56-5. Complications (%) Associated with
Chronic Kidney Disease During Pregnancy
Renal Insufficiency
Complication
Preserved
Function
Moderate
and
Severe Severe
Chronic
hypertension
25 30–70 50
Gestational
hypertension
20–50 30–50 75
Worsening renal
function
8–15 20–43 35
Permanent
dysfunction
4–5 10–20 35
Preterm delivery 7 30–60 73
Fetal-growth
restriction
8–14 30–38 57
Perinatal mortality 5–14 4–7 0
Data from Alsuwaida, 2011; Cunningham, 1990; Farwell,
2013; He, 2018; Imbasciati, 2007; Maruotti, 2012; Nevis,
2011; Piccoli, 2010, 2011; Stettler, 1992; Trevisan, 2004;
Zhang, 2015.Renal and Urinary Tract Disorders 1005
CHAPTER 56
Imbasciati, 2007; Jones, 1996). Despite a high incidence o
chronic hypertension, anemia, preeclampsia, preterm delivery,
and etal-growth restriction, perinatal outcomes were generally
acceptable. As shown in Figure 56-4, etal growth is requently
impaired and related to renal dysunction severity.
■ Management
Prenatal care or women with CKD incorporates several
important aspects. Frequent monitoring o blood pressure is
paramount, and serum creatinine levels and 24-hour protein
excretion are quantied as indicated. Bacteriuria is treated to
lower the risk o pyelonephritis and urther nephron loss. Protein-restricted diets are not recommended. In some women
with anemia rom chronic renal insuciency, a response is
seen with recombinant erythropoietin. However, hypertension is a common side eect. Serial sonography is perormed
to ollow etal growth. Te dierentiation between worsening
hypertension and superimposed preeclampsia is problematic.
Preliminary data indicate that the angiogenic biomarkers placental growth actor (PlGF) and its soluble receptor, soluble
ms-like tyrosine kinase 1 (sFlt-1), may be useul to separate
chronic rom gestational hypertension (Fishel Bartal, 2020).
Tis is described in Chapter 40 (p. 694).
■ LongTerm Effects
Pregnancy may accelerate CKD progression by augmenting
hyperltration and glomerular pressure to worsen nephrosclerosis (Bargman, 2018). Women with severe renal insu-
ciency have greater susceptibility. Jungers and associates
(1995) reported ew long-term pregnancy-related adverse
eects in 360 women with chronic glomerulonephritis and
antecedent normal renal unction. In a study rom Parkland
Hospital, 20 percent o pregnant women with moderate to
severe renal insuciency developed end-stage renal ailure by
a mean o 4 years (Cunningham, 1990). He and coworkers
(2018) conrmed these ndings in women who had stage 3
or 4 CKD.
As noted, progression is common or many women with
chronic renal disorders. At 1 year ater pregnancy, Jones and
Hayslett (1996) reported that 10 percent o the women had
developed end-stage renal ailure—stage 5 CKD. Similar
ndings in women with a median ollow-up o 3 years were
described by Imbasciati and colleagues (2007). By this time,
end-stage disease was apparent in 30 percent o women whose
prepregnancy serum creatinine was ≥1.4 mg/dL and who had
proteinuria >1 g/d.
Chronic proteinuria is also a marker or subsequent development o renal ailure. In one study, 20 percent o women
with chronic proteinuria discovered during pregnancy progressed to end-stage renal ailure within several years (Stettler,
1992). Another study reported that an equal number o nonpregnant women had identical loss o unction when similar
durations were compared (Zhang, 2015). It may be that pregnancy does not hasten an already predetermined declining
renal unction.
■ Dialysis During Pregnancy
Signicantly impaired renal unction is accompanied by sub-
ertility that may be corrected with chronic renal replacement
therapy—either hemodialysis or peritoneal dialysis (Wiles,
2019b). Not unexpectedly, maternal complications are common
and include severe hypertension, placental abruption, heart ailure,
and sepsis. o illustrate this, the outcomes o 233 pregnancies
in women undergoing dialysis are shown in Table 56-6. Te
high incidences o hypertension, low birthweight, and preterm
delivery result in a perinatal mortality rate o 250 per 1000.
Piccoli and associates (2016) perormed a systematic review and
described 681 pregnancies in 647 women undergoing dialysis.
O these, 616 had hemodialysis and 65 had peritoneal dialysis.
Tey chronicled a high incidence o hypertension, preterm delivery, and etal-growth restriction, and the perinatal mortality was
180 per 1000. Tey ound an inverse relationship between hours
o dialysis per week and adverse outcomes. Last, they reported
that hemodialysis was superior to peritoneal dialysis.
For the woman already undergoing either method o dialysis,
it seems reasonable to continue that method with consideration
or its increasing requency. In the woman who has never been
dialyzed, the threshold or initiation during pregnancy is unclear.
Hladunewich and colleagues (2016) recommend consideration
or dialysis when the creatinine clearance is 20 mL/min or less.
Extension o dialysis requency to ve to six times weekly may be
necessary to avoid abrupt volume changes that cause hypotension.
Hladunewich and coworkers (2011) recommend attention
to certain protocols that include replacement o substances lost
through dialysis. Multivitamin doses are doubled, and oral calcium and iron salts are provided along with sucient dietary
protein and calories. Chronic anemia is treated with erythropoietin. o meet pregnancy changes, extra calcium is added to
the dialysate along with less bicarbonate.
ACUTE KIDNEY INJURY
Previously termed acute renal ailure, acute kidney injury (AKI)
is now used to describe impairment o kidney unction over days
20 25
90th
50th
10th
30
Gestational age (weeks)
Birthweight (g)
35 40 45
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
FIGURE 56-4 Birthweight percentiles of infants born to 29 women
at Parkland Hospital with mild to moderate renal insufficiency—
serum creatinine 1.4–2.4 mg/dL (black points) and severe renal
insufficiency—serum creatinine ≥2.5 mg/dL (red points). (Data from
Cunningham, 1990; Stettler, 1992. Growth curves are those reported
by Alexander, 1996.)1006 Medical and Surgical Complications
Section 12
to weeks that leads to retention o nitrogenous and other waste
products normally excreted by the kidneys. Current denitions
include a rise in a serum creatinine level o at least 0.3 mg/dL
within 48 hours, or ≥50 percent increase rom baseline within
a week, or urine output reduced to <0.5 mL/kg per hour or
>6 hours (Waikar, 2018).
Criteria or diagnosis in pregnancy have not been standardized (Gonzalez Suarez, 2019). Most studies use a denition in
which serum creatinine levels rise ≥0.3 mg/dL rom baseline.
Animal studies have shown that pregnancy protects the kidney
rom acute ischemic injury (Popkov, 2018). Although the incidence o AKI in pregnancy has dropped substantially, it still occasionally causes signicant obstetrical morbidity and mortality.
In a Canadian study, the incidence was reported to be 2.68 per
10,000 births between 2009 and 2010 (Mehrabadi, 2014). Outcomes are available rom our older studies comprising a total
o 266 women with AKI (Drakeley, 2002; Nzerue, 1998; Sibai,
1990; urney, 1989). Approximately 70 percent had preeclampsia, 50 percent had obstetrical hemorrhage, and 30 percent had a
placental abruption. Almost 20 percent required dialysis, and the
maternal mortality rate approximated 15 percent.
Although obstetrical cases o AKI requiring dialysis are less
requent today, acute renal ischemia is still commonly associated
with severe preeclampsia and hemorrhage (Conti-Ramsden,
2019; Jim, 2017; Prakash, 2018). Notable contributors are placental abruption and hemolysis, elevated liver enzymes, and low
platelet count (HELLP) syndrome. Sepsis is another, especially
in resource-poor countries (Acharya, 2013). AKI also oten complicates acute atty liver o pregnancy. Nelson and colleagues
(2013) reported some degree o renal insuciency in virtually
all o 52 such women cared or at Parkland Hospital (Chap. 58,
p. 1034). Dehydration caused by severe hyperemesis gravidarum also can lead to AKI (Hill, 2002). Other causes include
thrombotic microangiopathies (Chap. 59, p. 1060).
■ Diagnosis and Management
In most women, renal ailure develops postpartum, thus management is usually not complicated by etal considerations.
Diagnostically, an acute rise in serum creatinine levels is most
oten due to renal ischemia. But oliguria also is an important
sign o acutely impaired renal unction. In obstetrical cases, both
prerenal and intrarenal actors commonly coincide. For example,
with total placental abruption, severe hypovolemia results rom
massive hemorrhage, and requently associated preeclampsia
causes preexistent renal ischemia (Chap. 40, p. 689).
When azotemia is severe and oliguria persists, some orm
o renal replacement treatment may be indicated. Hemoltration or dialysis is initiated beore patients markedly deteriorate,
and hemodynamic measurements are normalized. Medication
dose adjustments are imperative, and magnesium sulate is a
prominent example (Waikar, 2018). Early dialysis appears to
reduce the mortality rate appreciably and may enhance the
extent o renal unction recovery. With time, renal unction
usually returns to normal or near normal. Even so, women in
subsequent pregnancies have higher incidences o hypertension
and adverse etal outcomes (angren, 2017).
■ Prevention
AKI in obstetrics is most oten due to acute blood loss and
especially that associated with preeclampsia. Tus, it may oten
be prevented by the ollowing means:
1. Prompt and vigorous volume replacement with crystalloid
solutions and blood in instances o massive hemorrhage, such
as in placental abruption, placenta previa, uterine rupture,
and postpartum uterine atony (Chap. 44, p. 771).
2. Delivery or termination o pregnancies complicated by severe
preeclampsia or eclampsia, and careul blood transusion i
blood loss is more than average (Chap. 41, p. 712).
3. Close observation or early signs o sepsis and shock in
women with pyelonephritis, septic abortion, chorioamnionitis, or other pelvic inections (Chap. 50, p. 887).
4. Avoidance o loop diuretics to treat oliguria beore ensuring
that blood volume and cardiac output are adequate or renal
perusion.
5. Judicious use o vasoconstrictor drugs to treat hypotension,
and only ater it has been determined that pathological vasodilation is the cause.
TABLE 56-6. Pregnancy Outcomes in Women Undergoing Dialysis During Pregnancy
Pregnancies Pregnancy Outcomes (%)
Study (Year) N
Delivery
(weeks)
Birthweight
(g) Hypertension Hydramnios
Perinatal
Mortality
Surviving
Infants
Toma (1999) 54 31.9 1545 35 44 33 67
Chao (2002) 13 32 1540 72 46 31 69
Tan (2006) 11 31 1390 36 18 18 82
Chou (2008) 13 30.8 1510 57 71 50 50
Luders (2010) 52 32.7 1555 67 40 13 87
Shahir (2013) 13 NS 2130 19a 14 22 78
Jesudason (2014) 77 33.8 1750 NS NS 20 80
Approximate averages 233 ∼32 ∼1600 ∼50 ∼44 ∼25 ∼75
aPreeclampsia only.
NS = not stated.Renal and Urinary Tract Disorders 1007
CHAPTER 56
Irreversible ischemic renal ailure caused by acute cortical necrosis
has become exceedingly uncommon in obstetrics. Beore widespread availability o dialysis, it complicated a ourth o obstetrical
renal ailure cases (Grüneld, 1987; urney, 1989). Most cases
ollowed placental abruption, preeclampsia-eclampsia, and endotoxin-induced shock. Once common with septic abortion, this
is a rare cause in the United States today (Jim, 2017). Histologically, the lesion appears to result rom thrombosis o segments
o the renal vascular system. Te lesions may be ocal, patchy,
conuent, or gross. Clinically, renal cortical necrosis ollows the
course o acute renal ailure, and its dierentiation rom acute
tubular necrosis is not possible during the early phase. Te prognosis depends on the extent o the necrosis. Recovery o unction
is variable, and stable renal insuciency may result.
■ Obstructive Renal Failure
Rarely, bilateral ureteral compression by a very large pregnant
uterus obstructs ureters to cause severe oliguria and azotemia. An
example is shown in Figure 56-5. Brandes and Fritsche (1991)
reviewed 13 cases that were the consequence o a markedly
overdistended uterus. Tey described a woman with twins who
developed anuria and a serum creatinine level o 12.2 mg/dL
at 34 weeks’ gestation. Ater amniotomy, urine ow resumed
at 500 mL/h, and a rapid decline in serum creatinine levels to
normal range ollowed. Eckord and Gingell (1991) described
10 women in whom ureteral obstruction was relieved by stenting. Te stents were let in place or a mean o 15.5 weeks and
removed 4 to 6 weeks postpartum.
We have observed this phenomenon on several occasions. In our experience, women with previous urinary tract
surgery or reux are more likely to have such obstructions
(Satin, 1993). Partial ureteral obstruction may be accompanied by uid retention and signicant hypertension. When
the obstructive uropathy is relieved, diuresis ensues and
hypertension dissipates. In one woman with massive hydramnios (9.4 L) and an anencephalic etus, amniocentesis and
removal o some o the amnionic uid was ollowed promptly
by diuresis, a decline in the plasma creatinine concentration,
and an improvement o hypertension.
LOWER URINARY TRACT LESIONS
■ Urethral Diverticulum
Inrequently complicating pregnancy, this type o diverticulum
is thought to originate rom an enlarging paraurethral gland
abscess that ruptures into the urethral lumen (Fig. 56-6). As
inection clears, the remaining dilated diverticular sac and its
ostium into the urethra persist. Associated ndings may be
urine collecting within and then dribbling rom the sac, pain,
palpable mass, and recurrent urinary inections. In general, a
diverticulum is managed expectantly during pregnancy. Rarely,
drainage may be necessary, or surgery required (Iyer, 2013).
I additional antepartum evaluation is needed, MR imaging is
preerred or its superior sot-tissue resolution and ability to
dene complex diverticula (Dwarkasing, 2011; Pathi, 2013).
■ Urinary Tract Fistulas
Fistulas ound during pregnancy likely existed previously, but in
rare cases, they orm during pregnancy. In developed countries,
vesicovaginal fstula ollowing a McDonald cerclage has been
reported (Massengill, 2012). Tese stulas may also orm with
the prolonged obstructed labor that is more commonly seen in
resource-poor countries. In these cases, the genital tract is compressed between the etal head and bony pelvis. Brie pressure is
not signicant, but prolonged pressure leads to tissue necrosis and
subsequent stula ormation (Wall, 2012). Vesicouterine fstulas
that developed ater prior cesarean delivery have been described
(DiMarco, 2006; Manjunatha, 2012). Rarely, vesicocervical fstula
may ollow cesarean delivery or may orm i the anterior cervical
lip is compressed against the symphysis pubis (Dudderidge, 2005).
A B
FIGURE 56-5 A. Magnetic resonance image in a coronal plane
of a pregnant woman with unilateral hydronephrosis caused
by ureteral obstruction. The serum creatinine was 8 mg/dL and
decreased to 0.8 mg/dL after a percutaneous nephrostomy tube
was placed. B. Left kidney (arrow) and associated hydronephrosis
(asterisk) are again noted in this axial plane image.
FIGURE 56-6 Asymptomatic urethral diverticulum, seen as a midline bulge beneath the urethral meatus (arrow), identified during
initial prenatal care examination
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