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Acute renal failure in pregnancy
Hilary S. Gammill, MD; Arundhathi Jeyabalan, MD, MSCR
Objectives: To provide an evidence-based, up-to-date review
of the literature regarding the assessment and management of
acute renal failure that may affect women during pregnancy and
the postpartum period.
Design: A review of the current literature was performed.
Results: Acute renal failure is a rare complication of pregnancy
but is associated with significant morbidity and mortality. Management requires knowledge of the renal physiologic changes occurring
in pregnancy and the relevant diagnoses, both pregnancy-specific
and those that may coincidentally occur with pregnancy. In addition,
fetal effects must be taken into consideration.
A
cute renal failure in the setting
of pregnancy presents an important clinical challenge.
While pregnancy-related acute
renal failure (PR-ARF) has become a rare
occurrence in the developed world, it
continues to be associated with significant mortality and long-term morbidity.
The societal impact of this is particularly
pronounced given the young and productive status of these women as a whole.
The care of women with PR-ARF is challenging because there are two patients to
consider: the mother and her fetus. A
multidisciplinary approach to care is essential, with a team including critical
care specialists, maternal-fetal-medicine
specialists, nephrologists, and neonatology specialists.
Incidence of Acute Renal
Failure in Pregnancy
Different definitions of acute renal
failure (which have ranged from serum
creatinine levels of ⬎0.8 mg/dL to dialysis requirement) render comparison
across epidemiologic studies difficult.
Furthermore, populations vary signifi-
From Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences (HSG,
AJ), University of Pittsburgh Medical Center, Pittsburgh, PA.
Copyright © 2005 by the Society of Critical Care
Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/01.CCM.0000183155.46886.C6
S372
Conclusions: Ideal care for women with acute renal failure in
pregnancy or postpartum requires a multidisciplinary approach
that may include maternal-fetal medicine, critical care medicine, nephrology, and neonatology specialists.(Crit Care Med
2005; 33[Suppl.]:S372–S384)
KEY WORDS: renal failure; pregnancy; pregnancy complications;
acid-base homeostasis; prerenal ischemia; tubular necrosis; hemodialysis; renal replacement therapy; hemolysis, elevated liver
enzymes, and low platelet (HELLP) syndrome; preeclampsia
cantly in their demographics, referral
base, and standard of care. Accepting
these limitations, we can assess general
trends in the epidemiology and impact of
PR-ARF.
Since the 1960s, the overall incidence
of PR-ARF has decreased from 1/3000 to
1/15,000 –1/20,000. Similarly, the proportion of total cases of PR-ARF pregnancy has fallen from 20 – 40% in the
1960s to 2–10% in the 1980s (1–3). Coincident with these declines, there has
been little change in the overall mortality
and long-term morbidity rates. From the
1950s through the 1990s, overall mortality rates have ranged from 0 –30% with
no clear trend over time (2–5). The consistency of mortality may be attributable
to increased efficiency in the developed
world at prevention of cases of straightforward ARF; the patients who continue
to develop renal failure are sicker— often
with multiple system organ failure (3).
Long-term prognosis has also remained
fairly consistent over time, with full renal
recovery rates of 60 –90% (2, 4, 5).
The overall decrease in incidence has
been attributed to two main trends—the
legalization of abortion in most developed countries and the resulting decrease
in septic abortion, and the improvement
in accessible prenatal care with the attendant surveillance for preeclampsia and
other obstetrical complications, which
together account for a substantial portion
of PR-ARF (2, 3).
In the developing world, and in other
populations with limited access to prenatal care and to abortion services, PR-ARF
continues to be a significant problem,
with associated higher mortality and
morbidity. Epidemiologic data from India
suggest that PR-ARF continues to account for 20% of total ARF cases and that
mortality rates remain as high as 50% (6,
7). In an inner-city population in Atlanta,
a low renal recovery rate of approximately
50% raises concerns about access to care
in certain populations even in the United
States (8).
In addition to the estimated impact of
PR-ARF in previously healthy patients, it
is well-known that in women with underlying chronic renal dysfunction (baseline
serum creatine ⬎1.4 mg/dL), there is a
significantly increased risk of pregnancyrelated loss of renal function (43%), and
an estimated 10% of patients experience
rapid deterioration in renal function (9).
Prevention
To affect the overall incidence of disease,
primary prevention via improved access to
prenatal care is key. On the other hand,
affecting mortality and long-term renal recovery is the focus of acute care for these
patients, since early and appropriate management can prevent or limit irreversible
change. This will be our focus in this presentation.
To optimize acute care for pregnant
women, it is crucial to build on an understanding of the physiologic changes to
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
the renal system in pregnancy. We will
therefore review the renal physiology of
pregnancy, the evidence regarding efficacy and suitability of diagnostic and
therapeutic options for PR-ARF , and etiologies of ARF both specific to and coincident with pregnancy. We will also discuss fetal considerations in the setting of
maternal ARF.
Renal Physiology: Alterations in
Pregnancy
Physiologic changes to the renal system associated with pregnancy fall into
several categories of alterations: anatomical, hemodynamic, substrate handling,
and acid-base status.
From as early as the first trimester,
there is dilation of the renal collecting
system as well as enlargement of the kidneys overall. There is a laterality to these
changes, with more dramatic and ubiquitous effects seen on the right side, particularly with advancing gestation (10,
11). These alterations are thought to be
related to hormonal effects on ureteral
smooth muscle and to external compression of the ureters at the pelvic brim
(right greater than left) (12).
The hemodynamic changes affecting
renal blood flow are coincident with and
partially causative of some of the general
cardiovascular changes of pregnancy.
Very early decreases in peripheral vascular resistance in pregnancy are due in
large part to decreased renal vascular resistance that may be related to the effects
of maternal hormones such as relaxin.
This arteriolar underfilling is thought to
lead to a systemic response including
marked increases in cardiac output (approximately 50% above nonpregnant
baseline) and plasma volume (approximately 40% above baseline). Although
this increase in plasma volume is also
accompanied by an increase in red cell
mass, the former is more substantial of
the two, thus leading to a mild relative
anemia in pregnancy. The decrease in
peripheral vascular resistance also results
in lower blood pressure, with a nadir
around midgestation and a gradual return to baseline by term (12, 13).
There are also changes in glomerular
filtration rate (GFR) and renal plasma
flow. Both increase during the first half of
pregnancy and subsequently level off,
with increases on the order of 40 – 65%
for GFR and 50 – 85% for renal plasma
flow (Fig. 1). These changes predict the
decreases in serum creatinine levels that
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Figure 1. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during pregnancy.
Schematic based on data from Ref. 13.
are seen throughout gestation (12, 13).
Table 1 shows normal values for creatinine and other parameters in pregnancy.
There is a physiologic decrease in
plasma osmolality beginning in early gestation, reaching its nadir around the 10th
week of pregnancy and remaining stable
for the duration of pregnancy. This has
been attributed to a “resetting of the osmostat,” with an appropriate vasopressin
response around an altered threshold in
pregnancy (14). Potential causes for all of
these changes have been hypothesized,
including volume expansion; hormonal
factors including progesterone, prolactin,
and relaxin; and endothelial factors including endothelin and nitric oxide (12,
13).
In terms of substrate handling, some
degree of proteinuria (⬍300 mg/24 hrs)
is normal in advancing gestation and
does not indicate renal compromise. This
may be due to increased GFR and to an
alteration in the charge of the glomerular
membrane that increases membrane permeability to negatively charged proteins.
It is also common in pregnancy to have a
mild degree of glucosuria. Normally, glucose is freely filtered at the glomerulus
and reabsorbed in the proximal tubule. In
pregnancy, there is increased glucose filtration overall as GFR is increased, and
there seems to be some impairment in
resorption as well (12, 13).
The kidney plays an important role in
acid-base homeostasis. The primary acidbase alteration of pregnancy results from
an increase in minute ventilation, which
causes a relative respiratory alkalosis. Resulting from this, there develops a compensatory metabolic acidosis with a decline in serum bicarbonate levels as noted
in Table 1. This decrease in serum bicarbonate may limit the buffering capacity
in pregnancy (12, 13).
Table 1. Normal laboratory variables in pregnancy
Variable
Normal Value
in Pregnancy
HCO3
Urinary protein
Plasma osmolality
9.0 mg/dL (average)
0.5 mg/dL (average)
1 ⬃40% over baseline
1 ⬃25% over baseline
2 ⬃10 mm Hg below
baseline
18–20 mEq/L
Maximum 300 mg/24 hrs
2 ⬃10 mOsm/kg H2O
BUN
Cr
GFR
CrCl
PCO2
BUN, blood urea nitrogen; Cr, creatinine;
GFR, glomerular filtration rate; CrCl, creatinine
clearance.
From Refs. 13 and 108.
General Diagnostic Principles
Defining Acute Renal Failure. Conceptually, ARF has been described as “a
deterioration of renal function over a period of hours to days, resulting in the
failure of the kidney to excrete nitrogenous waste products and to maintain
fluid and electrolyte homeostasis” (15).
Specific diagnostic criteria have remained nebulous, and, as mentioned previously, this has clouded the literature
regarding ARF, particularly weakening
the generalizability of study conclusions
and rendering the translation of research
to bedside care more problematic. Recent
attempts to standardize these definitions
account for the limitations of commonly
used measures of renal function (serum
creatinine, urine output, GFR) including
their variability by patient age, gender,
size, and underlying renal function (16).
The Acute Dialysis Quality Initiative developed a model for diagnosis of ARF, as
shown in Figure 2 (17).
Categorizing Acute Renal Failure.
Traditionally, ARF has been divided into
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Figure 2. Diagnostic scheme for acute renal failure (ARF). The classification system includes separate
criteria for creatinine and urine output. The criteria that lead to the worst classification should be
used. Note that RIFLE-F is present even if the increase in serum creatinine (SCreat) is less than
three-fold so long as the new SCreat is ⱖ4.0 mg/dL (350 ␮mol/L) in the setting of an acute increase
of ⱖ0.5 mg/dL (44 ␮mol/L). The designation RIFLE-FC should be used in the case to denote “acute on
chronic” disease. Similarly, when RIFLE-F classification is reached by urine output (UO) criteria, a
designation of RIFLE-FO should be used to denote oliguria. The shape of the figure denotes the fact
that more patients (high sensitivity) will be included in the mild category, including some who do not
actually have renal failure (less specificity). In contrast, at the bottom, the criteria are strict and
therefore specific, but some patients will be missed. GFR, glomerular filtration rate; ARF, acute renal
failure. Reprinted with permission from Ref. 16.
three etiologies: prerenal, intrarenal, and
postrenal (15). Prerenal ARF occurs as a
result of decreased renal perfusion. This
can occur because of hypovolemia (as in
severe blood loss), hypotension (as in septic shock), or low cardiac output. If uncorrected, prerenal ARF can lead to intrinsic renal damage and intrarenal ARF.
Adequate and immediate correction of renal perfusion is the crucial therapeutic
intervention that can prevent this transition and ameliorate long-term damage.
Intrarenal ARF can also occur due to specific effects on the renal parenchyma via
toxin-mediated or immunologic mechanisms. Postrenal ARF reflects downstream obstruction of the genitourinary
tract. This can occur from obstruction of
both renal outflow tracts (as in urethral
obstruction) or of a unilateral tract if the
unobstructed kidney is nonfunctional. As
we understand more of the physiology of
ARF and of the complexity of multiple
organ disease, it becomes evident that
this system represents an oversimplification. However, until we can develop classification schemes more relevant to physiology and outcomes, this general
approach can be useful in guiding clinical
management (16).
Every patient presenting with PR-ARF
should undergo a detailed history, physical examination, and laboratory assessment. Urine electrolyte analysis can be
particularly useful in the categorization
of the type of renal failure (Table 2). As
renal perfusion diminishes, a functioning
kidney responds by increasing sodium resorption and decreasing sodium excretion. If intrinsic renal damage has occurred, however, this process is impaired.
The Role for Renal Biopsy. In a general population of nonpregnant patients
with ARF, those with less straightforward
presentations can benefit from renal biopsy. One study found that in approximately 70% of ARF cases, management
was altered by histology (18). In a nonpregnant population, the serious complication rate of renal biopsy is also reassuringly low at ⬍1% (19).
In pregnancy, we expect diagnoses to
be clinically discernable in the large majority of cases; therefore, we would anticipate that there would be a smaller role
for renal biopsy. Furthermore, theoretical concerns have been raised regarding
possible increased morbidity of the procedure in pregnancy. The primary utility
of renal biopsy in pregnancy is the identification of etiologies other than preeclampsia when patients present preterm
with renal failure. This is because the
only cure for preeclampsia is delivery.
Finding lesions other than those associated with preeclampsia has the potential
to identify patients who can be managed
by therapies other than delivery, thereby
minimizing iatrogenic preterm birth and
optimizing maternal treatment.
A review of the literature on renal biopsy in pregnancy shows complication
rates of approximately 1.6 – 4.4%, including perirenal bleeding requiring nephrectomy and perirenal hematoma; as many
Table 2. Categorization of acute renal failure
Prerenal
Proteinuria
Hemoglobinuria
Leukocyturia
Sediment
UNa, mEq/L
Fractional excretion of sodium,a (%)
Urine osmolality, mOsm/kg
Trace to none
—
—
Few hyaline casts
⬍20
⬍1
⬎500
Intrarenal
Mild to moderate
⫾
⫾
Granular or cellular casts; WBCs; RBCs
⬎40
⬎2
⬍350
Postrenal
Trace to none
⫾
⫾
No casts; WBCs; RBCs
Early appears prerenal, later postrenal
WBC, white blood cell; RBC, red blood cell; UNa, urine sodium; PCr, phosphocreatinine; PNa, plasma sodium; UCr, urine creatinine.
The fractional excretion of sodium is the fraction of sodium filtered at the glomerulus that is excreted in the urine. It is calculated by the formula
(UNa)(PCr)/(PNa)(UCr) 䡠 100.
a
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Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
as 17% of women had gross hematuria
(20). Most studies reported 0% mortality
rates, but one study did describe a maternal death (21). Packham and Fairley (22),
in 1987, addressed the safety and utility
of renal biopsy in pregnancy; their indications for biopsy included new-onset hematuria, proteinuria, or impaired renal
function in the first or second trimesters.
In a series of 111 biopsies in 104 women,
they reported a 97% tissue procurement
rate, one patient with a serious perirenal
hematoma, and four patients with transient hematuria or pain that resolved
spontaneously. In 80% of the patients
biopsied, a specific glomerulonephritis
was identified (22). Lindheimer and Davidson (23) reviewed these conflicting
data in 1987 and suggested that whereas
the overall safety profile of renal biopsy in
pregnancy is probably not significantly
greater than outside of pregnancy, the
procedure does have attendant risks, and
the indications for biopsy should be limited to situations “when there is sudden
deterioration in renal function before 32
wks gestation and no obvious cause is
apparent.” This philosophy, which intends to maximize the clinical relevance
of biopsy results, has since been adopted.
More recent series of renal biopsies
performed using the current method of
ultrasound guidance suggest that in a
well-selected population, histology specifically directs management in 66 –100%
of patients. Complication rates in these
studies ranged from perirenal hematoma
rates of 0 – 40%, with up to 25% of those
cases requiring transfusion, and there
were no maternal deaths (24,25). These
recent studies substantiate Lindheimer
and Davidson’s suggestion that renal biopsy has a role in pregnancy and that the
invasiveness of the procedure should be
factored into the decision whether to biopsy. The current state of neonatal care,
with excellent outcomes beyond 30 wks,
should perhaps lead us to reassess the
gestational age threshold for biopsy, considering when the implications of iatrogenic prematurity are most significant.
General Therapeutic Principles
Once an assessment of the type and
degree of ARF is made, the general principles of management involve the following: a) treatment of underlying causes; b)
prevention of further damage; and c) supportive measures until recovery may occur. Therapeutic measures directed at
specific pregnancy-related diagnoses are
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
detailed in the next section. Here, we will
focus on the management of ARF and
renal replacement therapy (RRT) by summarizing the general medical literature
and then discussing pregnancy-specific
considerations of each intervention.
Medical Management. General management of ARF begins with correction of
underlying etiological factors and removal of renal toxins (most commonly
aminoglycoside antibiotics and radiocontrast agents). Care must also be taken to
adjust the dosing of medications that are
renally cleared; one such agent commonly used in pregnancy is magnesium
sulfate, which is used for seizure prophylaxis in preeclampsia and for inhibition of
preterm labor. Prevention and treatment
of infection are crucial in this population,
as sepsis is the most common cause for
mortality in ARF. Following these measures, the single most important intervention is fluid management. The goal is
to restore and maintain renal perfusion
to reverse preischemic changes; even after tubular necrosis has ensued, the extent of further damage can be limited by
adequate perfusion. In most cases, clinical assessment can guide this therapy;
however, in more complicated cases, invasive hemodynamic monitoring may be
necessary (15).
Pharmacologic measures remain secondary therapies for the treatment or
amelioration of ARF. Low-dose dopamine
infusion has traditionally been used because of its vasodilatory effect on renal
arterioles and resultant increase in renal
blood flow. However, the current evidence suggests that this does not translate into any difference in clinical outcome. A large placebo-controlled trial
comparing low-dose dopamine to placebo
showed no differences in serum creatinine, need for renal replacement therapy,
or length of intensive care unit/hospital
stay (26). Meta-analyses of smaller studies have found similar results (27, 28).
Dopamine can trigger tachyarrhythmias,
pulmonary shunting, and gastrointestinal or digital necrosis (15). A particular
concern in pregnancy is the effect of vasoactive medications on uterine blood
flow and therefore the effects on the fetoplacental unit. There is evidence in animal models that dopamine infusion reduces uterine artery blood flow in both
normotensive and hypotensive settings.
Furthermore, dopamine may also inhibit
prolactin release and therefore has the
potential to negatively affect lactation
(29). Based on the lack of clinical benefit
and associated risks, there is no clear role
for dopamine infusion in the treatment of
ARF in pregnancy.
Loop diuretics increase renal intratubular flow rates, which may decrease intratubular obstruction and ameliorate resulting cellular damage. This has been
the rationale for the use of loop diuretics
in ARF. Furthermore, since nonoliguric
ARF has an overall better prognosis than
oliguric ARF, it seemed plausible that
converting an oliguric state to a nonoliguric one with the use of pharmacologic
diuresis might positively affect prognosis
(15). The published evidence in this regard is conflicting. There are data suggesting that diuretic therapy does not decrease the need for RRT or positively
affect mortality. A recent review points
out that although several observational
cohort studies suggest that diuretics may
be associated with an increased risk of
death or renal death, these results are
difficult to interpret due to their lack of
randomization (30). In a large, multiplecenter international cohort study, multivariate analyses showed no difference in
mortality rates among those patients
treated with diuretics (31). Based on this
evidence, the use of loop diuretics in the
treatment of ARF in a general medical
population is reserved for treatment of
volume overload, in an attempt to avoid
RRT. Specific fetal risks of diuretic use
have not been reported; however, any
agent that alters maternal hemodynamics
and has potential to affect uteroplacental
perfusion must be used with care in pregnancy.
Other agents that have been considered for use in ARF are listed in Table 3
(15, 29).
Hyperkalemia, metabolic acidosis, and
anemia are downstream effects of ARF
that may require specific treatment short
of RRT. Hyperkalemia can be treated with
potassium binding resins (polystyrene
sulfonate) or glucose and insulin (15).
There are no published data on polystyrene sulfonate in pregnancy, but due to
its mode of action and lack of absorption,
there is no physiologic reason to believe
that it would be harmful (32). Metabolic
acidosis in the setting of ARF can be
treated with sodium bicarbonate (15).
There are no specific pregnancy-related
contraindications to the use of glucose/
insulin or bicarbonate; however, the
compensatory metabolic acidosis of pregnancy must be accounted for in the use of
bicarbonate.
Anemia related to ARF is due to both
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Table 3. Other pharmacotherapeutics in acute renal failure (ARF)
Agent
Mechanism
Clinical Utility
Pregnancy Concerns
Calcium channel blockers
Renal vasodilation
Dopamine receptor
agonists
Atrial natriuretic peptide
Renal vasodilation
Theophylline
Adenosine antagonist
May help prevent renal damage from radiocontrast
agents in patients at risk
N-acetylcysteine
Free radical scavenger
Osmotic agents, e.g.
mannitol
Diuresis
May help prevent renal damage from radiocontrast
agents in patients at risk
Effective in the prevention of early myoglobinuric
renal failure
Renal vasodilation
No clinical benefit; may cause hypotension and
worsen ARF
No clinical benefit; may cause hypotension and
worsen ARF
No clear clinical benefit; there may be subsets of
patients who would benefit
Hypotension, decreased UPBF
No data; theoretic concern for
hypotension and decreased UPBF
No data; hemodynamically active, need
to watch for hypotension and
decreased UPBF
Transient neonatal jitteriness and
tachycardia immediately after
delivery if recently exposed; no longterm risks
Very limited data; appears safe
Very limited data; hemodynamically
active, need to watch for hypotension
and decreased UPBF
UPBF, uteroplacental blood flow.
From Refs. 15 and 29.
Table 4. Indications for the initiation of renal
replacement therapy
1. Volume overload
2. Hyperkalemia refractory to medical
management
3. Metabolic acidosis
4. Symptomatic uremia (including pericarditis,
neuropathy, mental status changes)
hemolysis (due to uremia-induced red
blood cell membrane fragility) and decreased hematopoiesis (due to decreased
erythropoietin levels) (33). Acute therapy
is generally via transfusion; however,
erythropoietin supplementation may play
a role if the process is prolonged. Exogenous erythropoietin can be associated
with hypertension (34), and increased
dosing is often needed in pregnancy to
attain therapeutic response (35–39).
Renal Replacement Therapy. If these
supportive measures are insufficient in
the management of ARF, the next step in
treatment is the initiation of RRT. The
classic indications for initiation of RRT in
ARF are listed in Table 4. There are several retrospective and a few prospective
studies looking at early vs. late initiation
of RRT in ARF which suggest that there
may be a survival benefit to early-onset
therapy (based on blood urea nitrogen
levels), with survival estimates of 39 –
75% in the early-onset groups and 12–
75% in the late-onset groups (40). A definitive large randomized trial is yet to be
done. Whether the threshold for initiation in pregnancy should be even lower
remains undetermined. Fetal effects and
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influences on uteroplacental blood flow
should be accounted for in this decision.
Once the decision has been made to
initiate RRT, consideration turns to the
method of its administration. Historically,
the standard method has been intermittent
hemodialysis. More recently, continuous
hemofiltration, sometimes combined with
hemodialysis, has become an alternative
option in the intensive care unit. The technical differences in the modalities of dialysis and filtration are summarized in Figure
3. In general, hemodialysis works via diffusion. A semipermeable membrane is bathed
in the patient’s blood on one side and a
dialysate solution on the other. Small molecules diffuse across the membrane, resulting in normalization of the patient’s plasma
solute concentrations. In contrast, hemofiltration makes use of convective flow. The
patient’s blood is filtered along a highly
permeable membrane, and water is filtered
out, nonspecifically bringing with it all
molecules of small molecular weight. After
filtration, a replacement fluid is administered with physiologic concentrations of
solutes (41).
These techniques can be used alone or
in combination. Each uses a circuit
through a hemofilter or dialyzer via an
efferent vessel (either artery or vein) and
an afferent vessel (a vein). The techniques
can be performed continuously or intermittently. The advantages of continuous
RRT (CRRT) are the ability to maintain
continuous control of volume and solute
loads and to avoid the hemodynamic fluctuations inherent in intermittent dialysis
(41,42).
Whether these advantages of CRRT
translate into decreased mortality and
improved renal preservation remains in
question. Available evidence supports the
efficacy and safety of CRRT, but so far, no
clear differences in overall outcomes have
been shown in a general population.
However, many of these trials were confounded by differences in overall health
status (43– 45). In a recent meta-analysis
that incorporated disease severity into a
multivariate model, Kellum and colleagues (46) found an overall decreased
risk of mortality with CRRT. These techniques may have particular benefit in specific populations, such as those who are
hemodynamically compromised. Pregnant women represent one such potential
patient group.
Dialysis in Pregnancy. The medical
literature reporting outcomes of dialysis
in pregnancy is limited to retrospective
reviews and case reports. The vast majority of these data are from patients with
chronic renal disease. Our ability to
translate medical evidence to the bedside
of the pregnant patient with acute renal
failure is, therefore, primarily extrapolative.
There have been substantial improvements in both fertility and successful
pregnancy rates in the CRF population
over the past three decades. Since the
first case report of a successful pregnancy
on dialysis in 1971 (47) and an initial case
series in the 1980s that suggested high
rates of preterm birth, low birth weight,
and refractory hypertension (48), the
overall prognosis for these patients has
improved significantly. However, these
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Figure 3. Methods of renal replacement therapy: Hemofiltration and hemodialysis. Schematic based on data from Refs. 41 and 42.
pregnancies continue to be high risk, and
outcomes remain quite variable.
There is evidence to suggest that these
improvements may be due to the recognition that increased dialysis dose may be
beneficial. Okundaye and colleagues (39)
in 1998 noted that an increase in the
number of hours of dialysis per week (beyond a threshold of twenty hours per
week) led to increasing survival and decreasing prematurity. Bagon and colleagues (49) found similar trends in their
national survey of dialysis centers in Belgium in 1998. In an attempt to minimize
the effects of uremia on pregnancy outcomes, they adjusted dialysis regimens
with the goal to attain maximum predialysis urea levels of ⱕ100 mg/dL. In doing so, a positive correlation was noted
between birth weight and “excess dialysis
hours” (the number of hours of dialysis
delivered minus the hours that would
have been given if the patient were not
pregnant) (49). These two publications
have influenced the prescription of dialysis for these patients internationally,
with the recommendation that an increased dialysis dose should be standard
of care for pregnant women (50). There
have been case reports since then of excellent perinatal outcome with intensive
dialysis (38, 51). Although the majority of
these studies assessed the role of hemodialysis, it should also be noted that peritoneal dialysis has been evaluated as well
in the setting of CRF in pregnancy, remains a viable option, and may have the
beneficial effect of minimizing maternal
hemodynamic changes (52, 53). Other
considerations for dialysis in pregnancy
are summarized in Table 5 (35–37).
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
As mentioned, the theoretical benefits
of CRRT might particularly benefit
women with PR-ARF. This is substantiated by the improved outcomes in the
pregnant patient with CRF using more
intensive dialysis. We also know that in
pregnancy, the hemodynamic shifts inherent with intermittent dialysis may
negatively affect uteroplacental perfusion
and increase risk of placental oxidative
stress with cyclic placental hypoperfusion
and reperfusion. This has the potential to
affect fetal growth and well-being. Furthermore, there has been concern that
uremia, which results in increased delivery of urea to the fetus and increases fetal
solute load, may lead to fetal diuresis and
resultant polyhydramnios, thereby increasing risks of preterm birth and preterm rupture of membranes (35–37, 54).
There has also been speculation that an
“azotemic intrauterine environment”
may contribute to the increased risk of
developmental delay seen in the CRF population (39). Although it is impossible to
separate out the relative contributions of
underlying disease and specific treatments in the causality of these adverse
outcomes, it is reasonable to speculate
that, by minimizing fluctuations in both
volume and solutes, CRRT could ameliorate these risks. However, there are no
published data to directly substantiate
any benefit of CRRT in pregnancy, nor do
leaders in the field know of unpublished
information (JA Kellum and R Bellomo,
personal communication, 2005).
Clearly, aggressive dialysis appears to
be safe and beneficial in a pregnant population in general, and this must be factored in to an assessment of risk and
benefit of early and intensive dialysis in
pregnancy with ARF.
Specific Etiologies of PR-ARF
To identify the underlying etiology of
ARF in pregnancy, it is important to consider both pregnancy-specific diagnoses
as well as other etiologies relevant to
reproductive age women that may be coincident with pregnancy. Several general
categories of pregnancy-specific ARF can
be delineated: hypertensive, thrombotic
microangiopathic, infectious, hypovolemic, and obstructive. Other intrinsic ARF
is generally associated with underlying
disease coincident with pregnancy. In the
following section, we review these categories and their component disease processes, with a focus on pathophysiology,
prognosis, and specific therapies.
Hypertension and Thrombotic
Microangiopathy
Preeclampsia/HELLP Syndrome. Preeclampsia is a pregnancy-specific condition diagnosed by new onset of hypertension and proteinuria after 20 wks of
gestation. Although it is one of the most
important causes of PR-ARF, the majority
of preeclamptic patients do not develop
renal failure. As we have come to better
understand the pathophysiology of preeclampsia, it appears that hypertension is
but a late clinical manifestation of the
disorder. Other underlying processes
such as endothelial dysfunction, inflammation, metabolic changes, enhanced
pressor responsiveness and vasoconstriction, and activation of the clotting casS377
Table 5. Specific considerations for dialysis in pregnancy
Variable
Hemodynamics
Serum urea levels
Maternal weight
Serum bicarbonate levels
Contractions
Vitamin and folate supplementation
Anemia/erythropoietin levels
Serum calcium levels
Pregnancy-Specific Concern
Careful attention to avoiding hypotension, fluid
fluctuations, and volume changes in pregnancy;
hypertension should also be treated if severe.
Maintain ⬍60 mg/dL.
Weight gain in pregnancy (baseline normal body mass
index) should be 1–2.5 kg total in the first trimester
and 0.3–0.5 kg/week in the second and third trimesters.
Remember physiologic metabolic acidosis (compensatory
for respiratory alkalosis) in pregnancy; bicarbonate is
normally decreased 4–5 mEq/L.
Scrutinize closely for preterm contractions and preterm
labor associated with dialysis.
Required in pregnancy and removed by dialysis; need to
increase supplementation.
If exogenous erythropoietin needed, therapeutic dosing is
generally higher in pregnancy.
Avoid hypercalcemia; calciferol doses often must be
reduced.
From Refs. 35–37 and 109.
cade may play a more important role in
the pathogenesis of this complex pregnancy-specific condition (55, 56). As
mentioned previously, preeclampsia is often associated with specific changes in
renal histology. The lesion pathognomonic of preeclampsia is glomeruloendotheliosis. This is characterized by a decrease in glomerular size with increased
cytoplasmic volume (due to inclusion of
electron-dense material) of the glomerular
endothelial cells and resultant decrease in
capillary lumen diameter, sometimes with
complete capillary obliteration. These
changes occur in up to 70% of patients
with preeclampsia and persist in the immediate postpartum period (57), but they appear to reverse completely in the vast majority of cases (58, 59). Coincident with
these histopathologic changes, there is an
overall decrease in GFR and effective renal
plasma flow in preeclampsia as compared
with normal pregnancy. These decrements
are approximately 32% and 24%, respectively, from normal late pregnancy levels
(13).In addition to the primary effects of
preeclampsia on renal function, preeclampsia can also predispose to PR-ARF
through secondary effects of relative intravascular volume depletion, vasoconstriction, and activation of the inflammatory and coagulation cascades. In this
setting, the superimposed insults of hemorrhage (e.g., abruption or postpartum
hemorrhage) can have a more significant
effect on renal perfusion, thus increasing
risks of renal deterioration. Several studies have found that patients with pregnancy complications superimposed on
S378
preeclampsia are at increased risk for the
development of ARF, suggesting that processes that further reduce intravascular
volume or that predispose to thrombotic
microangiopathy may be pivotal (60). Entities specifically associated with preeclampsia-associated ARF include abruption, disseminated intravascular
coagulation (DIC), HELLP syndrome (a
variant of severe preeclampsia involving
hemolysis, elevated liver enzymes, and
low platelets which occurs in 4 –14% of
cases of preeclampsia) (61, 62), and antiphospholipid antibody syndrome (63–
66). It follows that in preeclampsiarelated ARF, the primary pathologic
process is acute tubular necrosis, with
the most severe cases at risk for renal
cortical necrosis (67).
As in the general literature regarding
ARF, studies evaluating the incidence of
and prognosis for PR-ARF attributable to
preeclampsia are greatly limited by lack
of standard definitions, differences in
standard of care, and difficulties in generalizability. Two of the most comprehensive recent studies suggest an overall
incidence of ARF in preeclampsia of 1.5–
2%, although definitions have varied (63,
64). Another study suggested that this
incidence increases significantly to ⬎7%
in patients with HELLP syndrome (65).
Maternal mortality rates in these studies
were 0 –10%, and perinatal mortality
rates were 34 – 41%. In terms of renal
prognosis, short-term dialysis rates were
10 –50%. These three studies followed patients long-term, for an average of 4 yrs,
and the need for long-term RRT de-
pended on renal and hypertensive status
entering pregnancy; none of the previously healthy preeclamptic patients required therapy. In contrast, of women
with preexisting hypertension or renal
disease, 40 – 80% required long-term dialysis, and several of these patients ultimately died of end-stage renal disease
(63– 65).
As with any case of ARF, treatment
must first include treating underlying
disorders. Preeclampsia is a progressive,
multisystemic disease process, as mentioned previously. To date, there is no
effective treatment strategy aside from
delivery of the fetus and placenta. Therefore, in the case of preeclampsia-related
ARF, delivery is indicated. The mode of
delivery (vaginal vs. cesarean) depends on
all clinical factors; beyond this, the principles of management are primarily supportive and include replacement of blood
products as indicated, maintenance of intravascular volume, and renal replacement therapy as needed.
Acute Fatty Liver of Pregnancy. Acute
fatty liver of pregnancy (AFLP) is a disorder characterized by rapidly progressive
hepatic failure in late gestation. It was
initially described by Stander and Cadden
(68) in 1934 and was considered extremely rare and frequently fatal for both
mother and baby. The incidence of AFLP
has increased (now possibly as high as
1/7,000 births), and maternal and perinatal mortality have decreased (in two recent series, there were no maternal
deaths, and perinatal mortality was 7%)
(69, 70). This is likely due to earlier diagnosis and intervention. Patients typically present with nausea, vomiting, malaise, and occasionally mental status
changes. Laboratory evaluation frequently demonstrates hyperbilirubinemia, moderate elevations in
transaminases, elevated ammonia levels,
and hypoglycemia (67, 71).The diagnosis
of AFLP is made after excluding other
etiologies such as gall bladder disease and
acute hepatitis. Many patients with AFLP
have coincident diagnoses of preeclampsia or HELLP syndrome, and the metabolic abnormalities of AFLP can help to
make this differentiation (69). Rarely,
liver biopsy is needed to confirm the diagnosis, although the potential for clotting abnormalities in these patients
should factor into the decision to biopsy.
Other manifestations of AFLP include
DIC (which is associated with decreased
antithrombin III levels), major intraabdominal bleeding, central diabetes inCrit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Table 6. General principles in the differential diagnosis of preeclampsia, acute fatty liver of pregnancy (AFLP), thrombotic thrombocytopenic purpura (TTP),
and hemolytic uremic syndrome (HUS)
Onset
Primary/unique clinical
manifestation
Purpura
Fever
Hemolysis
Coagulation studies
Hypoglycemia
vWF multimers
Preeclampsia/HELLP
TTP
HUS
AFLP
Usually third trimester
Hypertension and proteinuria
Median 23 wks
Neurologic symptoms
Often postpartum
Renal involvement
Absent
Absent
Mild
Variable
Absent
Absent
Present
Present
Severe
Normal
Absent
Present
Absent
Absent
Severe
Normal
Absent
Present
Close to term
Nausea, vomiting,
malaise
Absent
Absent
Mild
Prolonged abnormal
Present
Absent
HELLP, hemolysis, elevated liver enzymes, and low platelets; vWF, von Willebrand factor.
From Refs. 75–78, 82, and 86.
sipidus, pancreatitis, and renal manifestations (67, 69 –71).
The renal dysfunction seen in AFLP is
likely multifactorial. One study suggested
that modest elevations in serum creatinine
levels indicative of mild insufficiency precede many of the clinical manifestations of
the disease (69). Microvesicular fatty infiltration of hepatocytes occurs in some patients because of inherited defects in mitochondrial ␤-oxidation of fatty acids. A
particular mutation in long-chain 3-hydroxyacyl coenzyme A dehydrogenase causing an enzyme deficiency in both mother
and fetus predisposes to AFLP (72). It is
hypothesized that this abnormal fatty acid
oxidation could lead to fatty infiltration of
tissues other than the liver, including the
kidney. Hepatorenal syndrome may also
contribute, and in patients who experience
hemorrhage and significant volume depletion, acute tubular necrosis can result. In
all published series, renal recovery in survivors of AFLP was complete (67, 69, 70).
As in preeclampsia, the only curative
intervention for AFLP is delivery. Recovery tends to be more prolonged for AFLP;
rarely are there any long-term sequelae.
Additional supportive measures, including correction of coagulopathy, maintenance of intravascular volume, and treatment of superimposed infections, are
crucial. RRT is rarely indicated (67, 69 –
71).
Amniotic Fluid Embolism. Amniotic
fluid embolism, a rare but dramatic clinical entity, can also be a cause of PR-ARF.
Amniotic fluid embolism, which is also
referred to as an anaphylactoid syndrome
of pregnancy, is the acute onset of hypoxia, respiratory failure, cardiogenic
shock, and DIC in pregnancy (73), occurring primarily during labor (70% of cases).
The maternal mortality rate of amniotic
fluid embolism is estimated to be ⬎60%,
with a similar perinatal mortality rate, and
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
most survivors (85%) suffer neurologic
sequelae (74). Due to the syndrome’s associated DIC, cardiac dysfunction, and hemorrhage causing intravascular volume depletion, ARF is a factor to consider in all
immediate survivors, and careful attention
to volume resuscitation is crucial.
Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome.
Thrombotic thrombocytopenic purpura
(TTP) and hemolytic uremic syndrome
(HUS) are disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and systemic ischemia and
multiple organ failure (75–78). Although
not specific to pregnancy, these disorders
are often included in the differential diagnosis of preeclampsia/HELLP syndrome
with ARF. Classically, TTP is identified by a
pentad of clinical findings: thrombocytopenia, hemolytic anemia, fever, neurologic
abnormalities, and renal dysfunction (79).
HUS was noted to be similar, but with less
dramatic neurologic involvement and more
significant renal manifestations. Often difficult to differentiate from severe preeclampsia (Table 6) (80), these disorders
occur in pregnancy at least as much as in
the general population, (75) and some authors report that pregnancy-related TTP/
HUS accounts for 10 –25% of overall cases
(76, 77). The overall incidence of TTP/HUS
in pregnancy has been estimated to be
1/25,000 births (75).Pathophysiologically,
TTP/HUS is thought to result from intravascular thrombi that cause consumption
of platelets, fragmentation of red blood
cells, and variable systemic ischemia (77).
Large, multimeric forms of von Willebrand’s factor are found in these patients,
and there is some evidence that a plasma
protease that normally cleaves these multimers may be genetically absent, deficient or may be inhibited by an acquired
autoantibody (81, 82).
Acute renal failure occurs in two
thirds of these patients (76). A number of
retrospective reviews of TTP/HUS in
pregnancy have been conducted. Maternal mortality has decreased over time and
ranges between 8 – 44%; similarly perinatal mortality has also decreased but remains substantial, between 30 – 80% (75,
83, 80). One study reviewed the experience at Parkland Hospital between 1972
and 1997. Their overall mortality rates
were fairly low; however, long-term morbidity and mortality were quite significant in the average 9-yr follow-up period.
The majority of these patients had persistent renal insufficiency and hypertension,
in the long term many of them required
dialysis and transplantation, and at the
time of their publication one had died of
end-stage renal disease (75). Long-term
neurologic sequelae are also possible with
TTP/HUS (83). Other pregnancy-specific
complications include fetal growth restriction, fetal distress and intrauterine
demise, and recurrence with future pregnancy (75–77, 83). Although TTP/HUS
can occur at any time during pregnancy
or postpartum, the median gestational
age at onset is about 23 wks, tending to
occur earlier than in preeclampsia (77).
Plasmapheresis is the cornerstone of
therapy for TTP/HUS, associated with a
decrease in mortality from 90% to 10 –
20% (84). Other modalities, albeit with
less demonstrated benefit, include glucocorticoids, antiplatelet agents, and, for
refractory cases, splenectomy or vincristine (76, 77). There is no clear benefit
from delivery (75), and anticoagulation
with heparin is potentially harmful (76).
Supportive measures including fluids,
blood transfusion (with caution in administration of platelets as this can exacerbate intravascular occlusion), and RRT
are essential components of therapy as
well (76, 77)
Often, TTP/HUS is diagnosed in the
S379
postpartum period, in patients with an
initial diagnosis of severe preeclampsia
who have worsening renal status, further
hematologic decompensation, or multisystemic ischemia despite delivery (76).
Postpartum Idiopathic ARF. Cases of
PR-ARF confined to the postpartum period that do not meet specific criteria for
TTP, HUS, preeclampsia, or AFLP have
been grouped into a category of idiopathic postpartum ARF (67, 85). Recently, it seems clear that these patients
fall along the spectrum of thrombotic microangiopathy with predominantly renal
manifestations. There are no specific
therapeutic principles regarding this entity; rather, patients should be treated
according to their likely underlying etiology, with supportive care and plasmapheresis if clinically indicated (75, 86).
Infection/Sepsis
Sepsis from any cause can lead to hypotension and decreased renal perfusion,
thus resulting in prerenal ischemia and potentially acute tubular necrosis. The most
common causes of sepsis in pregnancy include pyelonephritis, chorioamnionitis,
and pneumonia. Pyelonephritis is the most
common infectious complication of pregnancy. Although the incidence of asymptomatic bacteriuria is not increased in
pregnancy, there is a higher likelihood of
ascending infection and pyelonephritis
(87). In pregnancy, pyelonephritis is also
associated with a higher risk of systemic
inflammation and sepsis. These elevated
risks can be attributed to several of the
physiologic adaptations of the renal system
to pregnancy, including ureteral dilation,
bladder wall flaccidity, and increased sensitivity to bacterial endotoxin-induced tissue
damage. Although pyelonephritis can lead
to sepsis and ARF in both the pregnant and
nonpregnant host, there is an increased
risk of ARF due to pyelonephritis in pregnancy independent of the presence or absence of sepsis. One historical study showed
that 25% of women with pyelonephritis
in pregnancy demonstrated a significant
decrement in GFR without sepsis (88). The
most common organisms involved in pyelonephritis in pregnancy are Escherichia
coli, Proteus mirabilis, and Klebsiella
pneumoniae. Pseudomonas aeruginosa,
group B streptococci, and enterococci are
also potential pathogens (89).
As mentioned, septic abortion was
once a significant contributor to ARF in
pregnancy. With the legalization of abortion and subsequent decrease in inciS380
dence, this has become a less important
contributor. However, cases of septic
abortion associated with spontaneous and
therapeutic abortion still occur. We have
recently seen a case in our own institution of sepsis with ARF in a septic abortion possibly associated with chorionic
villus sampling (an invasive procedure
used for chromosomal assessment in
cases of increased risk of fetal aneuploidy). There is some suggestion of a
higher incidence of renal cortical necrosis in sepsis associated with septic abortion than would be expected with sepsis
in general (90). These infections tend to
be polymicrobial, often involving anaerobic species. The most common organisms
involved in bacteremia due to ascending
infection are E. coli, group B streptococci, anaerobic streptococci, Bacteroides species, Clostridium species, and
enterococci (91).
In terms of therapeutic considerations, in all of these cases, general supportive measures, including hydration
and blood pressure support, should be
accompanied by antibiotic therapy. The
choice of antibiotic coverage should be
governed by the organisms involved, either based on epidemiologic knowledge
or documented by culture results. For
the polymicrobial ascending infections of
the genital tract, including septic abortion, antibiotic selection should be broadspectrum, ensuring adequate anaerobic
coverage. For cases of septic abortion or
chorioamnionitis, it should be noted that
antibiotic penetration of the uterine cavity is suboptimal and that evacuation of
the uterine contents is necessary for effective treatment.
Volume Depletion
Volume depletion can lead to ARF by
causing prerenal ischemia. In pregnancy,
the most common cause of volume depletion of this magnitude is obstetrical hemorrhage, which can occur at any gestational age. Severe cases of hyperemesis
gravidarum leading to refractory nausea
and vomiting, if insufficiently treated,
could also result in poor renal perfusion.
Obstetrical hemorrhage can occur early
in pregnancy due to spontaneous or induced abortion. More commonly, third
trimester hemorrhage from placenta previa, placental abruption, or postpartum
hemorrhage are contributors to significant blood loss, putting patients at risk of
ARF. These processes can also be associated with consumptive coagulopathy,
which can exacerbate the process, or disseminated intravascular coagulation,
which can cause direct intrarenal damage. Treatment of hemorrhage sufficient
to cause prerenal ischemia includes volume support, replacement of blood products, and correction of coagulopathy. In
the antepartum setting, delivery is indicated, either vaginally or by cesarean
section, depending on the clinical picture from an obstetric perspective. In
the postpartum setting, the underlying
problem must be addressed. For surgical bleeding, exploratory laparotomy
and repair may be indicated. In cases of
uterine atony leading to hemorrhage,
medical therapy with uterotonics, or if
refractory, surgical intervention may be
necessary.
Hyperemesis gravidarum is a common
complication of pregnancy, with 70 – 85%
of pregnant women experiencing some
degree of nausea and vomiting (92) and
1–2% of women with severe symptoms,
often including a loss of 5% of body
weight (93). In general, hyperemesis can
be managed with oral antiemetic medications. In a small subset of patients, aggressive management with enteral and/or
parenteral nutrition and hydration may
be required. In rare cases, severe hypovolemia can result in prerenal ischemia and
ARF. A recent case report discusses one
such patient, who required short-term
RRT and supportive care and subsequently went on recover full renal function (94).
Obstruction
The gravid uterus can provide significant compression of the genitourinary
system, particularly in settings of uterine
overdistention such as polyhydramnios,
multiple gestation, or uterine fibroids. Although rare, there have been several case
reports of PR-ARF in these scenarios (95–
106). Maternal genitourinary anomalies
or prior surgery can also increase susceptibility to such processes, particularly
in the setting of a unilateral kidney or
collecting system (106). Nephrolithiasis
is another potential obstructive cause
of ARF to consider, as the incidence of
stones is the same as in a population of
nonpregnant reproductive age women
(107). Approaches to treatment of obstructive PR-ARF include cystoscopy
and retrograde ureteral stent placement
or percutaneous nephrostomy (95, 96,
106). If the clinical situation suggests
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Table 7. Differential diagnosis of intrinsic renal disease in reproductive-aged women
Category/Location
Mechanism/Subtype
Specific Diagnoses
Tubular necrosis
Continuum with prerenal ischemia
Vasculitis
Systemic vascular inflammation with renal
involvement
Acute glomerulonephritis
Ischemia
Toxins
Wegener’s granulomatosis
Thromboembolic disease
Scleroderma
Immunoglobulin A nephropathy
Thin basement membrane disease
Lupus nephropathy
Hereditary nephritis
Mesangial proliferative glomerulonephritis
Postinfectious glomerulonephritis
Lupus nephropathy
Rapidly progressive glomerulonephritis
Fibrillary glomerulonephritis
Membranoproliferative glomerulonephritis
Focal glomerulosclerosis
Minimal change disease
Membranous nephropathy (including lupus)
Diabetic nephropathy
Late-stage postinfectious glomerulonephritis
Drug/toxin (e.g. penicillins, cephalosporins, sulfonamides, rifampin,
ciprofloxacin, NSAIDs, thiazide diuretics, furosemide, cimetidine,
phenytoin, allopurinol)
Autoimmune disease, e.g. lupus
Infiltrative disease, e.g. sarcoidosis
Infectious disease, e.g., legionnaire’s disease or hantavirus
Focal glomerulonephritis
Diffuse glomerulonephritis
Nephrotic syndrome
Acute interstitial nephritis
Hypersensitivity response
NSAIDs, nonsteroidal anti-inflammatory drugs.
From Refs. 15 and 110 –112.
Table 8. Differentiation of preeclampsia and acute glomerulonephritis
Gestational age
Hypertension
Systemic manifestations
Urine sediment
Acute Glomerulonephritis
Preeclampsia
Any
Present
Collagen-vascular disease,
preceding infection
Hematuria, RBC casts, oval
fat bodies
Most third trimester
Present
Neurologic, hematologic, or
hepatic involvement
Isolated proteinuria or
findings of ATN (brown
granular casts, renal
tubular cells)
⬎300 mg/24 hrs (mild), ⬎5
g/24 hrs (severe)
7
7
7
7
Proteinuria
⬎2 g/24 hrs
Complement levels
ANA
Antistreptolysin-O titers
Other autoantibodies
2
1
1
1
RBC, red blood cell; ATN, acute tubular necrosis; ANA, antinuclear antibody.
From Ref. 113.
that delivery would be appropriate, this
may ameliorate genitourinary obstruction (97, 99, 102–105). Published case
reports indicate excellent prognosis for
general recovery and restoration of renal function once the obstruction is
relieved (95, 97–99, 101–106). Rarely,
hemodialysis has been suggested as a
temporizing measure until more definitive treatment of the obstruction can
be achieved (103).
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Other Intrinsic Renal Dysfunction
As mentioned, the evaluation of a
pregnant patient with ARF must take into
consideration those etiologies that may
occur coincident with gestation but may
not be specific to pregnancy. Table 7 outlines this differential diagnosis in detail,
with a focus on those diseases that are
more common in reproductive-aged
women. Differentiating glomerular dis-
ease from preeclampsia and other forms
of PR-ARF can be challenging. Some of
the distinguishing characteristics are
summarized in Table 8.
Fetal Considerations
The adverse perinatal outcomes associated with PR-ARF are typically due to
altered uteroplacental hemodynamics.
Intravascular support is a crucial component of management of these patients,
both in limiting renal damage and in
preserving uterine blood flow. Attention to
volume status, the fetal effects of medications, and maternal solute load are key
components of the treatment of PR-ARF.
Fetal heart rate monitoring allows evaluation of fetal status and placental oxygen
delivery. In viable gestations (⬎23–24 wks
gestation), fairly frequent fetal heart rate
monitoring may be indicated, with acceptable regimens ranging from periodic assessments with nonstress tests or biophysical profiles to continuous monitoring. The
intensity of fetal heart rate monitoring
should follow the acuity of the clinical situation, with those patients with hemodynamic instability most closely followed.
Although fetal heart rate monitoring
is an invaluable tool, it should be emphasized that maternal stability must be enS381
sured before an intervention specifically
for fetal benefit should be undertaken. If
preterm delivery is likely to be indicated
for maternal benefit, the administration
of glucocorticoids (betamethasone, e.g.)
should be considered to minimize neonatal morbidity related to prematurity. In
terms of neonatal management, the most
common problems that these neonates
face are those of prematurity. They also
tend to have high intravascular solute
loads, which puts them at risk for osmotic diuresis and dehydration. In the
anticipation and management of these
problems, specialized neonatologists and
a tertiary care neonatal intensive care
unit are important components of the
multidisciplinary team.
8.
9.
10.
11.
12.
13.
CONCLUSION
The uniqueness of medical care in
pregnancy lies in two areas: the body’s
dramatic alterations caused by gestation
and the need to treat two patients simultaneously, only one directly accessible.
Renal failure in pregnancy presents particular challenges, in that it occurs in a
system physiologically altered from baseline and can occur due to disease processes that are specific to pregnancy and
as yet incompletely understood. It is crucial for physicians caring for these patients to have a broad knowledge of physiologic alterations in the renal system in
pregnancy, to apply the best evidencebased diagnostic and therapeutic strategies for these disease processes, and to
consider both maternal and fetal effects
of disease and therapy.
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