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Official reprint from UpToDate

www.uptodate.com 2017 UpToDate

Acute kidney injury (acute renal failure) in pregnancy

Author: Phyllis August, MD, MPH


Section Editors: Charles J Lockwood, MD, MHCM, Paul M Palevsky, MD
Deputy Editor: Alice M Sheridan, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2017. | This topic last updated: Feb 01, 2017.

INTRODUCTION Acute kidney injury (AKI) is the abrupt loss of kidney function, resulting in the retention of
urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes.
The term, AKI, has largely replaced acute renal failure (ARF), reflecting the recognition that smaller declines
in kidney function that do not result in overt organ failure are of substantial clinical relevance and are
associated with increased morbidity and mortality.

AKI during pregnancy can be caused by any of the disorders leading to AKI in the general population. There
are also, however, pregnancy complications characteristic of each trimester that can be associated with
kidney injury [1,2]. This topic reviews causes of AKI that are most commonly encountered during pregnancy.
Causes of AKI in the general population are discussed elsewhere. (See "Diagnostic approach to the patient
with subacute kidney injury in an outpatient setting", section on 'Major causes and pathogenesis of kidney
disease'.)

Nephrolithiasis during pregnancy is discussed elsewhere. (See "Nephrolithiasis during pregnancy".)

DEFINITION AKI is defined by the abrupt loss of kidney function. Several consensus definitions of AKI
have been developed for use in the general population in order to provide a uniform, quantitative definition of
AKI. These include the RIFLE and Acute Kidney Injury Network (AKIN) definitions and the Kidney Disease:
Improving Global Outcomes (KDIGO) modifications of the AKIN definition. (See "Diagnostic approach to the
patient with subacute kidney injury in an outpatient setting", section on 'Major causes and pathogenesis of
kidney disease'.)

However, it is not clear that the consensus criteria for AKI are useful in pregnancy. This is because, during
pregnancy, glomerular filtration rate (GFR) increases significantly (by approximately 50 percent), resulting in a
lower baseline serum creatinine compared with similarly healthy, nonpregnant individuals (see "Renal and
urinary tract physiology in normal pregnancy", section on 'Increase in GFR'). Most obstetricians do not
routinely check the serum creatinine either prior to or early in pregnancy. Thus, seemingly "normal" serum
creatinine levels (eg, 0.7 to 0.9 mg/dL) may represent significant increases from baseline, which may not be
appreciated at the time of presentation.

EPIDEMIOLOGY AKI during pregnancy is uncommon in the developed world. The true incidence is
difficult to estimate because of varying diagnostic criteria. Most reviews estimate that, in countries with
adequate antenatal care, only approximately 1 in 20,000 pregnancies are affected by AKI severe enough to
require renal replacement therapy (RRT) [3]. The incidence may be considerably higher in countries where
antenatal care is less available and where illegal abortions are performed [4]. Although some single-center
series from India and Africa report an incidence as high as 10 to 20 percent, a series from Egypt reported an
incidence of AKI requiring dialysis of only 0.6 percent of 5600 deliveries [5].
ETIOLOGIES The most common causes of AKI during pregnancy depend on the trimester. AKI early in
pregnancy (<20 weeks) is most often due to:

Prerenal disease due to hyperemesis gravidarum (see "Clinical features and evaluation of nausea and
vomiting of pregnancy", section on 'Evaluation')

Acute tubular necrosis (ATN) resulting from a septic abortion (see "Unsafe abortion", section on
'Infection')

AKI associated with either viral (eg, influenza) or bacterial infection and/or sepsis

Several disorders can lead to AKI later in pregnancy [1,2]. These include:

Severe preeclampsia (see "Preeclampsia: Clinical features and diagnosis")

Severe preeclampsia with HELLP syndrome (see "HELLP syndrome")

Thrombotic thrombocytopenic purpura (TTP, acquired or hereditary) or complement-mediated hemolytic


uremic syndrome (HUS) (see "Thrombocytopenia in pregnancy", section on 'Thrombotic microangiopathy
(TMA)')

Acute fatty liver of pregnancy (AFLP) (see "Acute fatty liver of pregnancy")

ATN or acute cortical necrosis associated with hemorrhage (placenta previa, placenta abruption,
prolonged intrauterine fetal death, or amniotic fluid embolism) (see "Clinical features, diagnosis, and
course of placenta previa" and "Placental abruption: Clinical features and diagnosis" and "Amniotic fluid
embolism syndrome")

In addition to these conditions, acute pyelonephritis and, less commonly, urinary tract obstruction have been
associated with AKI in pregnant women. (See "Urinary tract infections and asymptomatic bacteriuria in
pregnancy", section on 'Acute pyelonephritis'.)

AKI that is related to pregnancy may also occur in the postpartum period. This may be due to causes listed
above that were present prior to delivery that have not resolved (eg, preeclampsia, HELLP syndrome,
atypical HUS). AKI secondary to ATN may develop due to hemodynamic stress associated with either
hemorrhage or sepsis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used routinely for postpartum analgesia. We have seen
AKI associated with NSAID use after delivery, particularly when there are additional risk factors such as
volume depletion or preeclampsia.

Individual etiologies are discussed below.

Preeclampsia with or without HELLP Preeclampsia is the most common cause of AKI during pregnancy.
Preeclampsia refers to the new onset of hypertension and either proteinuria or other signs of systemic
disease (including thrombocytopenia, elevated liver enzymes, AKI, pulmonary edema, cerebral and/or visual
disturbances), usually after 20 weeks of gestation in a previously normotensive woman (table 1). The clinical
features are extensively discussed elsewhere. (See "Preeclampsia: Clinical features and diagnosis".)

Preeclampsia complicates 3 to 5 percent of all pregnancies; the risk is increased among women with
hypertension, diabetes, or chronic kidney disease (CKD) from any cause [6]. (See "Preeclampsia: Clinical
features and diagnosis".)

In most women with preeclampsia, the glomerular filtration rate (GFR) decreases on average by only 30 to 40
percent, which results in only minor increases in the serum creatinine [7]. AKI requiring renal replacement
therapy (RRT) is uncommon except in patients with very severe preeclampsia (eg, characterized by severe
hypertension, thrombocytopenia, elevated liver enzymes, pulmonary edema, cerebral and visual symptoms)
and when there is accompanying hemorrhage and ischemic ATN.

Preeclampsia may occur with or without features of the HELLP syndrome. The HELLP syndrome refers to a
variant in which hemolysis, low platelet count, and elevated liver enzymes are present. (See "HELLP
syndrome", section on 'Laboratory criteria'.)

AKI is more common when preeclampsia is accompanied by features of the HELLP syndrome [7]. Some
studies suggest that AKI occurs in 3 to 15 percent of cases of preeclampsia associated with the HELLP
syndrome [8-10]. AKI is often multifactorial in such cases since, in addition to the renal changes characteristic
of preeclampsia such as endothelial cell swelling and injury, there is associated coagulopathy, which may
result in bleeding, placental abruption, and ATN.

By contrast, based on clinical observation, AKI is much less common in patients with severe preeclampsia
without features of HELLP syndrome, although there are few published studies that have examined
incidence.

In some cases, preeclampsia is first diagnosed in the postpartum period, without documentation of
antepartum hypertension and proteinuria [11,12]. Preeclampsia that is first observed in the postpartum period
is particularly difficult to distinguish from microangiopathic disorders such as TTP or HUS. This issue is
discussed below. (See 'Diagnostic approach and differential diagnosis' below.)

Severe preeclampsia is an indication for urgent delivery (see "Preeclampsia: Management and prognosis").
The renal and extrarenal abnormalities typically begin to resolve spontaneously within two to three days
postpartum, and complete recovery of GFR occurs within eight weeks postpartum [13,14]. Moderately
increased albuminuria (ie, between 30 and 300 mg/day [20 to 200 mcg/min], formerly called
"microalbuminuria") may persist [15]. Women who develop preeclampsia may be at increased risk of
developing end-stage renal disease (ESRD) later in life, but the absolute risk is small. This issue is discussed
elsewhere. (See "Preeclampsia: Management and prognosis", section on 'End-stage renal disease'.)

The treatment of the HELLP variant of preeclampsia is discussed elsewhere. (See "HELLP syndrome",
section on 'Management'.)

Thrombotic thrombocytopenic purpura or hemolytic uremic syndrome TTP and HUS are both
characterized by the presence of microthrombi of fibrin and/or platelets in multiple organ systems, particularly
the kidney and the brain (table 2). Presenting features include thrombocytopenia and microangiopathic
hemolytic anemia without another apparent cause and, in many patients, neurologic and/or renal
abnormalities [16,17]. (See "Acquired TTP: Clinical manifestations and diagnosis" and "Thrombocytopenia in
pregnancy", section on 'Thrombotic microangiopathy (TMA)'.)

Pregnancy may trigger either TTP or HUS [18-20].

TTP is caused by an acquired or constitutional deficiency of activity of ADAMTS13, a Von Willebrand factor-
processing protein [21]. Pregnancy has been shown to induce the onset or relapse of ADAMTS13 deficiency-
related TTP [7]. (See "Acquired TTP: Management following recovery from an acute episode and during
remission", section on 'Pregnancy after an episode of TTP' and "Hereditary thrombotic thrombocytopenic
purpura (TTP)", section on 'Pregnancy'.)

Atypical or complement-mediated HUS is caused by mutations in genes that encode complement-regulatory


proteins, which result in uncontrolled complement activation [18-20,22]. Pregnancy is a well-recognized
trigger for episodes of HUS in patients with these mutations. A study from France reported 21 patients with
pregnancy-associated HUS (defined by the presence of hemolytic anemia, thrombocytopenia, and AKI).
Multiple different mutations of genes encoding complement-regulating proteins were identified in 18 of 21
patients (86 percent) [20]. Serum C3 levels were low at the time of the first complement assessment in 12 of
21 patients (57 percent). (See "Complement-mediated hemolytic uremic syndrome".)

TTP and HUS differ in the timing of onset. TTP associated with ADAMTS13 deficiency occurs predominantly
in the second and third trimesters [20]. ADAMTS13 levels tend to fall during the last two trimesters of
pregnancy, which could contribute to the time course of development of TTP [23-26]. Pregnancy-associated
HUS more commonly occurs in the postpartum period; in a report from France, of 21 patients with pregnancy-
associated HUS, 15 occurred after delivery [20].

AKI may occur in either pregnancy-associated TTP or HUS, though it is more common among patients with
HUS. In the French series of 21 patients, 17 (81 percent) required hemodialysis at least transiently, and 16
(76 percent) had ESRD at last follow-up [20].

Postpartum HUS may follow a normal pregnancy or be preceded by findings indistinguishable from
preeclampsia [11,12,27].

TTP or HUS that initially occurs in nonpregnant women may relapse during a subsequent pregnancy, and
recurrent TTP or HUS may develop during successive pregnancies [20,23,28,29]. However, most subsequent
pregnancies are uncomplicated, and most children survive [20,30]. (See "Acquired TTP: Initial treatment".)

The diagnosis is generally made by clinical features. Renal biopsy is usually not performed, at least initially,
due to the increased risk for bleeding associated with thrombocytopenia.

However, if the thrombocytopenia and hemolysis resolve but AKI persists, a kidney biopsy may help to define
the etiology and prognosis for recovery of renal function. A diagnostic approach to pregnant women with AKI
is discussed below. (See 'Diagnostic approach and differential diagnosis' below.)

The treatment of pregnancy-associated TTP or HUS is discussed elsewhere (see "Thrombocytopenia in


pregnancy", section on 'Management decisions'). Plasma exchange is an important component of treatment
of AKI due to either pregnancy-associated TTP or HUS. In cases of pregnancy-associated HUS, if AKI fails to
improve after three to five treatments with plasma exchanges, treatment with eculizumab, a monoclonal,
humanized immunoglobulin G (IgG) that inhibits complement activation, may be effective [7]. Since HUS
usually presents in the postpartum period, issues related to fetal toxicity due to eculizumab are not a concern.
(See "Complement-mediated hemolytic uremic syndrome", section on 'Treatment'.)

Treatment of AKI is supportive (see 'Treatment' below). In addition to plasma exchange and supportive care,
delivery may be indicated if the patient is still pregnant, especially if the diagnosis is not certain. This is
because the main differential diagnosis is usually preeclampsia with HELLP syndrome, which will improve
after delivery.

Most patients requiring dialysis, however, are postpartum, and considerations for RRT are similar to
nonpregnant adults with AKI (see "Renal replacement therapy (dialysis) in acute kidney injury in adults:
Indications, timing, and dialysis dose"). Blood pressure control is important and may enhance endothelial cell
recovery.

Acute fatty liver of pregnancy Acute fatty liver (fatty infiltration of hepatocytes without inflammation or
necrosis) is a rare complication of pregnancy that is associated with AKI in up to 60 percent of cases [2,31].

The pathogenesis of AFLP is discussed elsewhere. (See "Acute fatty liver of pregnancy" and "Acute fatty liver
of pregnancy", section on 'Pathogenesis'.)

Patients present in the third trimester with clinical signs consistent with preeclampsia (hypertension,
thrombocytopenia) but also have hypoglycemia, hypofibrinogenemia, liver function test abnormalities with
hyperbilirubinemia, and a prolonged partial thromboplastin time (PTT) in the absence of abruptio placentae
[32]. (See "Acute fatty liver of pregnancy".)

The diagnosis should be suspected based on clinical features [33]. The laboratory and radiographic
evaluation is discussed elsewhere. (See "Acute fatty liver of pregnancy", section on 'Diagnosis'.)

Therapy consists of treatment of disseminated intravascular coagulation (DIC) and immediate delivery of the
fetus [2,32] (see "Acute fatty liver of pregnancy", section on 'Treatment and course'). The laboratory
abnormalities frequently begin to improve within one to two days after delivery [32].

Renal cortical necrosis Renal cortical necrosis used to be an important cause of AKI associated with
catastrophic obstetric emergencies such as placental abruption with massive hemorrhage or amniotic fluid
embolism [7]. Renal cortical necrosis is now generally considered quite rare in developed countries, however,
and is responsible for only 1 to 2 percent of all cases of AKI [7]. Renal cortical necrosis may still be an
important clinical problem in parts of the world where obstetric hemorrhage occurs remote from a hospital
setting and is thus difficult to manage [2,34-37]. In addition, a report of 18 cases that occurred in France
between 2009 and 2013 suggests that renal cortical necrosis remains a significant potential complication of
postpartum hemorrhage even in developed countries [38]. The authors of this case series postulated that the
use of the procoagulant, tranexamic acid (which was prescribed to control obstetric hemorrhage), may have
been related to the development of renal cortical necrosis in some patients.

Both primary DIC and severe renal ischemia (leading to endothelial damage and secondary fibrin deposition)
likely cause renal cortical necrosis. When endothelial injury does occur, the local release of nitric oxide
(endothelium-derived relaxing factor) normally minimizes the degree of thrombus formation by diminishing
platelet aggregation. If, however, the endothelial dysfunction is so great that nitric oxide release is impaired,
then the tendency to thrombosis will be accelerated [39].

Patients with cortical necrosis present with the abrupt onset of oliguria or anuria following an obstetric
catastrophe. Oliguria or anuria is frequently accompanied by gross hematuria, flank pain, and hypotension
[34,35]. The triad of oliguria/anuria, gross hematuria, and flank pain is unusual in the other causes of renal
failure in pregnancy.

The diagnosis can usually be established by ultrasonography or computed tomography (CT) scanning, which
demonstrates hypoechoic or hypodense areas in the renal cortex [34].

No specific therapy has been shown to be effective in this disorder. Many patients require dialysis, but 20 to
40 percent have partial recovery with a creatinine clearance that stabilizes between 15 and 50 mL/min [35].

Acute pyelonephritis Although kidney function is generally well maintained during episodes of acute
pyelonephritis (in the absence of septicemia or hypotension), pregnant women are at increased risk for AKI
[2,40]. Acute pyelonephritis may develop at any time during pregnancy but is more likely to occur after 20
weeks. A retrospective series of 94 cases from Nepal reported that most cases of pyelonephritis occurred
during the second trimester [41].

The diagnosis is generally made by clinical features, urinalysis, and urine culture. (See "Urinary tract
infections and asymptomatic bacteriuria in pregnancy", section on 'Diagnosis and evaluation'.)

Kidney biopsy is generally not performed for diagnosis in patients who have AKI and characteristic features of
pyelonephritis.

The treatment of pregnancy-associated pyelonephritis is discussed elsewhere. (See "Urinary tract infections
and asymptomatic bacteriuria in pregnancy", section on 'Management'.)

Renal function generally improves after treatment with antibiotics, although recovery after appropriate
antimicrobial therapy may be incomplete due to irreversible injury.

Urinary tract obstruction Relaxation of ureteral smooth muscle and pressure on the ureters by the gravid
uterus result in mild to moderate dilatation of the collecting systems [42,43]. (See "Renal and urinary tract
physiology in normal pregnancy".)

This functional hydronephrosis, which tends to be more prominent on the right, is detectable by
ultrasonography but is not usually associated with renal dysfunction.

Occasionally, obstruction of the ureters by the uterus is sufficient to cause renal failure [42]. The diagnosis
can be established in some cases by the normalization of renal function in the lateral recumbent position
(which relieves pressure on the ureters by the uterus) and its recurrence when supine.

AKI resolves with relief of obstruction. This may be achieved by insertion of a ureteric stent or delivery of the
fetus [43].

Postpartum AKI associated with nonsteroidal anti-inflammatory drugs Nonsteroidal anti-inflammatory


drugs (NSAIDs) are routinely used for postpartum analgesia, particularly after cesarean section. Although
uncommon, among such patients who receive NSAIDs, AKI may develop if there are predisposing conditions
such as volume depletion or preeclampsia. (See "NSAIDs: Acute kidney injury (acute renal failure)".)

DIAGNOSTIC APPROACH AND DIFFERENTIAL DIAGNOSIS AKI is generally identified by laboratory


evaluation showing an increased serum creatinine above the patients usual baseline. (See 'Definition'
above.)

Identification of the cause of AKI is important in order to administer appropriate therapy. The diagnostic
approach to patients with AKI during pregnancy is similar during all stages of pregnancy.

First, it is important to exclude causes of AKI that are unrelated to pregnancy, including glomerulonephritis,
interstitial nephritis, or acute tubular necrosis (ATN) due to toxins, drugs, or hemodynamic stress. The
evaluation of AKI due to causes unrelated to pregnancy is discussed elsewhere. (See "Diagnostic approach
to the patient with subacute kidney injury in an outpatient setting", section on 'Major causes and pathogenesis
of kidney disease'.)

Careful review of the medical history and prior laboratory values is important. A history of systemic lupus
erythematosus or laboratory evidence of proteinuria or a reduced estimated glomerular filtration rate (eGFR)
prior to pregnancy may suggest worsening of an underlying glomerular disease that is unrelated to
pregnancy. (See "Diagnostic approach to the patient with subacute kidney injury in an outpatient setting",
section on 'Major causes and pathogenesis of kidney disease'.)

The history may also suggest causes of prerenal AKI (such as hyperemesis gravidarum) or ATN/acute
cortical necrosis (such as sepsis or hemorrhage related to obstetrical complications including placenta previa,
prolonged intrauterine fetal death, or amniotic fluid embolism).

All medications should be carefully reviewed.

In addition to a careful history, physical examination, and medication review, we obtain the following tests:
Dipstick urinalysis and microscopic analysis of sediment
Quantitation of protein excretion by either 24-hour urine collection or by protein-to-creatinine ratio
Urine culture
Hemoglobin level and platelet count with peripheral blood smear to evaluate for microangiopathic
hemolysis and thrombocytopenia
Total, direct, and indirect bilirubin concentration; haptoglobin; and lactate dehydrogenase (LDH) to
evaluate for hemolysis
Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
Renal ultrasound

In addition to these tests, in patients with urinary findings consistent with glomerulonephritis, laboratory tests
that suggest other, non-pregnancy-related causes of AKI may also be obtained (such as complement proteins
C3, C4, antinuclear antibody [ANA], antineutrophil cytoplasmic antibody [ANCA], etc). (See "Diagnostic
approach to the patient with subacute kidney injury in an outpatient setting", section on 'Major causes and
pathogenesis of kidney disease' and "Differential diagnosis and evaluation of glomerular disease".)

Among patients who are determined to have hemolysis and thrombocytopenia, other tests are indicated to
evaluate for thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS; such as
measurement of complement proteins and ADAMTS13 levels). (See "Acquired TTP: Clinical manifestations
and diagnosis", section on 'Diagnostic evaluation' and "Hereditary thrombotic thrombocytopenic purpura
(TTP)", section on 'Diagnosis' and "Complement-mediated hemolytic uremic syndrome", section on
'Evaluation'.)

ATN and acute cortical necrosis are suggested by the history (sepsis or hemorrhage) and by microscopic
analysis of urinary sediment, which often shows pigmented granular casts and renal tubular epithelial cells.
The diagnosis of cortical necrosis can usually be established by ultrasonography or computed tomography
(CT) scanning, which demonstrate hypoechoic or hypodense areas in the renal cortex [34].

Renal calcifications on plain film of the abdomen also suggest renal cortical necrosis, but this is a late
consequence of healing and is not visible for one to two months. Renal biopsy or arteriography also can be
performed to diagnose cortical necrosis, but these invasive procedures are not required in most cases.

Acute pyelonephritis is suggested by flank pain, nausea/vomiting, fever, and/or costovertebral angle
tenderness and may occur in the presence or absence of cystitis symptoms. (See "Urinary tract infections
and asymptomatic bacteriuria in pregnancy", section on 'Clinical manifestations' and "Urinary tract infections
and asymptomatic bacteriuria in pregnancy", section on 'Diagnosis'.)

AKI in late pregnancy suggests a possible diagnosis of preeclampsia with or without HELLP syndrome, TTP
or HUS, or acute fatty liver of pregnancy (AFLP). There is considerable overlap in symptoms and laboratory
abnormalities among these disorders. However, an accurate diagnosis is usually made by careful
consideration of the clinical presentation in association with the pattern of laboratory abnormalities. Renal
biopsy is rarely, if ever, required to distinguish between preeclampsia with or without HELLP syndrome, AFLP,
and TTP or HUS and is usually not performed, at least initially, because of thrombocytopenia. A renal biopsy
may be indicated for confirmation of diagnosis and for prognosis if AKI persists after resolution of the
thrombocytopenia and hemolysis.

Some useful distinguishing criteria are summarized below [11,12,27]:

Timing of onset and rate of recovery Preeclampsia with or without HELLP syndrome typically
develops in the late third trimester, including the intrapartum period. Only a few percent of cases develop
in the postpartum period, usually in the first 24 to 48 hours. Preeclampsia does not occur before 20
weeks gestation in nonmolar pregnancies, except occasionally in the presence of thrombophilias, such
as the antiphospholipid antibody syndrome.

TTP is most common in the second and third trimesters, while HUS most commonly presents
immediately postpartum. (See "Pathophysiology of acquired TTP and other primary thrombotic
microangiopathies (TMAs)".)

AFLP develops in the third trimester and resolves within one to two weeks postpartum.

In patients with preeclampsia with or without HELLP syndrome, spontaneous recovery or improvement
within the first two or three days following delivery is typical, while progression of thrombocytopenia,
hemolytic anemia, and renal failure suggest pregnancy-associated atypical HUS. (See "Preeclampsia:
Management and prognosis".)

Clinical and laboratory features Both the HELLP variant of severe preeclampsia, TTP, and HUS are
characterized by microangiopathic hemolysis and low platelet count. The presence of elevated liver
enzymes and right upper-quadrant pain is strongly suggestive of HELLP syndrome or AFLP and is an
uncommon feature of TTP or HUS. In contrast to patients with TTP, who have severe deficiencies of
ADAMTS13, plasma levels of ADAMTS13 are only mildly or moderately reduced in patients with HELLP
syndrome [44]. (See "HELLP syndrome", section on 'Patient presentation'.)

The thrombotic state in some patients with antiphospholipid antibodies may be indistinguishable from
TTP or HUS. (See "Clinical manifestations of antiphospholipid syndrome".)

AFLP has many features of both TTP or HUS and HELLP syndrome and can be particularly difficult to
identify. (See 'Acute fatty liver of pregnancy' above.)

Women with AFLP often complain of loss of appetite and nausea. They have elevated liver enzymes,
similar to those with HELLP syndrome; however, they frequently develop more severe jaundice,
azotemia, and consumptive coagulopathy. Hypoglycemia is also a feature of AFLP and has been
attributed to liver dysfunction.

TREATMENT Treatment is targeted to the specific cause of AKI and is discussed above. The treatment of
AKI is supportive. Dialysis should be initiated based on the usual criteria for patients in the nonobstetric
setting and particularly if oliguria is present. (See "Renal replacement therapy (dialysis) in acute kidney injury
in adults: Indications, timing, and dialysis dose" and "Overview of the management of acute kidney injury
(acute renal failure)".)

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Basics topics (see "Patient education: Acute kidney failure (The Basics)")

SUMMARY AND RECOMMENDATIONS


Pregnancy-related acute kidney injury (AKI) is uncommon in developed countries. The incidence may be
considerably higher in countries where antenatal care is less available and where illegal abortions are
performed. (See 'Introduction' above and 'Epidemiology' above.)

Causes of AKI early in pregnancy (before 20 weeks) include prerenal disease due to hyperemesis
gravidarum and acute tubular necrosis (ATN) resulting from a septic abortion or other bacterial or viral
infection.

Causes of AKI in late pregnancy (after 20 weeks) include preeclampsia, thrombotic thrombocytopenic
purpura (TTP), hemolytic uremic syndrome (HUS), acute fatty liver of pregnancy (AFLP), ATN or acute
cortical necrosis, acute pyelonephritis, and, rarely, urinary tract obstruction. Nonsteroidal anti-
inflammatory drugs (NSAIDs) may cause AKI in the postpartum period. (See 'Etiologies' above.)

The evaluation of pregnancy-associated AKI includes urinalysis and microscopic analysis of sediment;
quantitation of protein excretion by either 24-hour urine collection or by protein-to-creatinine ration; urine
culture; hemoglobin level and platelet count with peripheral blood smear; total, direct, and indirect
bilirubin concentration; serum haptoglobin; serum lactate dehydrogenase (LDH); serum aspartate
aminotransferase (AST) and/or alanine aminotransferase (ALT); and a renal ultrasound. (See 'Diagnostic
approach and differential diagnosis' above.)

Many causes of pregnancy-associated AKI are distinguished by history and physical examination,
urinalysis, and occasionally ultrasound. It is often difficult to distinguish among preeclampsia with or
without HELLP syndrome, TTP, HUS, and AFLP because of the overlap in symptoms and laboratory
abnormalities. However, an accurate diagnosis is usually made based upon clinical features. A renal
biopsy is rarely performed in this setting. (See 'Diagnostic approach and differential diagnosis' above.)

The specific treatment for pregnancy-associated AKI depends on the underlying etiology:

Preeclampsia-associated AKI is an indication for delivery. Delivery generally results in completely


recovery of renal function, although moderately increased albuminuria (formerly called
"microalbuminuria") may persist. (See 'Preeclampsia with or without HELLP' above.)

TTP- or HUS-associated AKI is primarily treated with plasma exchange. (See "Acquired TTP: Initial
treatment".)

AFLP-associated AKI includes the treatment of disseminated intravascular coagulation (DIC) and
delivery of the fetus. (See 'Acute fatty liver of pregnancy' above.)

In addition to targeted therapies of specific underlying disorders, the treatment of AKI is supportive.
Dialysis should be initiated based on the usual criteria for patients in the nonobstetric setting. (See
"Overview of the management of acute kidney injury (acute renal failure)" and "Renal replacement
therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose" and
'Treatment' above.)

ACKNOWLEDGMENT The authors and the editorial staff at UpToDate would like to acknowledge James
N George, MD, who contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES
1. Krane NK. Acute renal failure in pregnancy. Arch Intern Med 1988; 148:2347.
2. Grnfeld JP, Pertuiset N. Acute renal failure in pregnancy: 1987. Am J Kidney Dis 1987; 9:359.
3. Nwoko R, Plecas D, Garovic VD. Acute kidney injury in the pregnant patient. Clin Nephrol 2012; 78:478.
4. Najar MS, Shah AR, Wani IA, et al. Pregnancy related acute kidney injury: A single center experience
from the Kashmir Valley. Indian J Nephrol 2008; 18:159.
5. Kamal EM, Behery MM, Sayed GA, Abdulatif HK. RIFLE classification and mortality in obstetric patients
admitted to the intensive care unit with acute kidney injury: a 3-year prospective study. Reprod Sci
2014; 21:1281.
6. Umans JG. Obstetric nephrology: preeclampsia--the nephrologist's perspective. Clin J Am Soc Nephrol
2012; 7:2107.
7. Fakhouri F, Vercel C, Frmeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies
in pregnancy. Clin J Am Soc Nephrol 2012; 7:2100.
8. Drakeley AJ, Le Roux PA, Anthony J, Penny J. Acute renal failure complicating severe preeclampsia
requiring admission to an obstetric intensive care unit. Am J Obstet Gynecol 2002; 186:253.
9. Acharya A, Santos J, Linde B, Anis K. Acute kidney injury in pregnancy-current status. Adv Chronic
Kidney Dis 2013; 20:215.
10. Sibai BM, Ramadan MK, Usta I, et al. Maternal morbidity and mortality in 442 pregnancies with
hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993;
169:1000.
11. McCrae KR, Samuels P, Schreiber AD. Pregnancy-associated thrombocytopenia: pathogenesis and
management. Blood 1992; 80:2697.
12. McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic
purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher 2001; 16:202.
13. Martin JN Jr, Blake PG, Perry KG Jr, et al. The natural history of HELLP syndrome: patterns of disease
progression and regression. Am J Obstet Gynecol 1991; 164:1500.
14. Sibai BM, Villar MA, Mabie BC. Acute renal failure in hypertensive disorders of pregnancy. Pregnancy
outcome and remote prognosis in thirty-one consecutive cases. Am J Obstet Gynecol 1990; 162:777.
15. McDonald SD, Han Z, Walsh MW, et al. Kidney disease after preeclampsia: a systematic review and
meta-analysis. Am J Kidney Dis 2010; 55:1026.
16. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927.
17. George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010;
116:4060.
18. Bresin E, Rurali E, Caprioli J, et al. Combined complement gene mutations in atypical hemolytic uremic
syndrome influence clinical phenotype. J Am Soc Nephrol 2013; 24:475.
19. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and
familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010; 5:1844.
20. Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in
the era of complement gene mutations. J Am Soc Nephrol 2010; 21:859.
21. Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause
thrombotic thrombocytopenic purpura. Nature 2001; 413:488.
22. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361:1676.
23. Dashe JS, Ramin SM, Cunningham FG. The long-term consequences of thrombotic microangiopathy
(thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy. Obstet Gynecol
1998; 91:662.
24. Mannucci PM, Canciani MT, Forza I, et al. Changes in health and disease of the metalloprotease that
cleaves von Willebrand factor. Blood 2001; 98:2730.
25. Vesely SK, George JN, Lmmle B, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-
hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective
cohort of 142 patients. Blood 2003; 102:60.
26. Martin JN Jr, Bailey AP, Rehberg JF, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies:
1955-2006. Am J Obstet Gynecol 2008; 199:98.
27. Weiner CP. Thrombotic microangiopathy in pregnancy and the postpartum period. Semin Hematol 1987;
24:119.
28. Ezra Y, Rose M, Eldor A. Therapy and prevention of thrombotic thrombocytopenic purpura during
pregnancy: a clinical study of 16 pregnancies. Am J Hematol 1996; 51:1.
29. Mokrzycki MH, Rickles FR, Kaplan AA, Kohn OF. Thrombotic thrombocytopenic purpura in pregnancy:
successful treatment with plasma exchange. Case report and review of the literature. Blood Purif 1995;
13:271.
30. Vesely SK, Li X, McMinn JR, et al. Pregnancy outcomes after recovery from thrombotic
thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion 2004; 44:1149.
31. Castro MA, Fassett MJ, Reynolds TB, et al. Reversible peripartum liver failure: a new perspective on
the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases.
Am J Obstet Gynecol 1999; 181:389.
32. Usta IM, Barton JR, Amon EA, et al. Acute fatty liver of pregnancy: an experience in the diagnosis and
management of fourteen cases. Am J Obstet Gynecol 1994; 171:1342.
33. Ibdah JA, Yang Z, Bennett MJ. Liver disease in pregnancy and fetal fatty acid oxidation defects. Mol
Genet Metab 2000; 71:182.
34. Black RM. Vascular diseases of the kidney. In: Pathophysiology of Renal Disease, 2nd ed., Rose BD
(Ed), McGraw-Hill, New York 1987. p.349.
35. Matlin RA, Gary NE. Acute cortical necrosis. Case report and review of the literature. Am J Med 1974;
56:110.
36. Ali A, Ali MA, Ali MU, Mohammad S. Hospital outcomes of obstetrical-related acute renal failure in a
tertiary care teaching hospital. Ren Fail 2011; 33:285.
37. Prakash J, Vohra R, Wani IA, et al. Decreasing incidence of renal cortical necrosis in patients with acute
renal failure in developing countries: a single-centre experience of 22 years from Eastern India. Nephrol
Dial Transplant 2007; 22:1213.
38. Frimat M, Decambron M, Lebas C, et al. Renal Cortical Necrosis in Postpartum Hemorrhage: A Case
Series. Am J Kidney Dis 2016; 68:50.
39. Shultz PJ, Raij L. Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular
thrombosis. J Clin Invest 1992; 90:1718.
40. Thompson C, Verani R, Evanoff G, Weinman E. Suppurative bacterial pyelonephritis as a cause of
acute renal failure. Am J Kidney Dis 1986; 8:271.
41. Sharma P, Thapa L. Acute pyelonephritis in pregnancy: a retrospective study. Aust N Z J Obstet
Gynaecol 2007; 47:313.
42. Fried AM. Hydronephrosis of pregnancy: ultrasonographic study and classification of asymptomatic
women. Am J Obstet Gynecol 1979; 135:1066.
43. Brandes JC, Fritsche C. Obstructive acute renal failure by a gravid uterus: a case report and review. Am
J Kidney Dis 1991; 18:398.
44. Lattuada A, Rossi E, Calzarossa C, et al. Mild to moderate reduction of a von Willebrand factor cleaving
protease (ADAMTS-13) in pregnant women with HELLP microangiopathic syndrome. Haematologica
2003; 88:1029.

Topic 7237 Version 14.0


GRAPHICS
Criteria for the diagnosis of preeclampsia

Systolic blood pressure 140 mmHg or diastolic blood pressure 90 mmHg on two occasions at
least four hours apart after 20 weeks of gestation in a previously normotensive patient

If systolic blood pressure is 160 mmHg or diastolic blood pressure is 110 mmHg, confirmation within
minutes is sufficient

and

Proteinuria 0.3 g in a 24-hour urine specimen or protein/creatinine ratio 0.3 (mg/mg)(30 mg/mmol)

Dipstick 1+ if a quantitative measurement is unavailable

OR

New-onset hypertension with the new onset of any of the following (with or without proteinuria):

Platelet count <100,000/microL

Serum creatinine >1.1 mg/dL (97.2 micromol/L)

Liver transaminases at least twice the upper limit of the normal concentrations for the local laboratory

Pulmonary edema

Cerebral or visual symptoms (eg, new-onset and persistent headaches not responding to usual doses of
analgesics; blurred vision, flashing lights or sparks, scotomata)

* Each measured as mg/dL.

Adapted from: American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy.
Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on
Hypertension in Pregnancy. Obstet Gynecol 2013; 122:1122.

Graphic 79977 Version 22.0


Thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS),
and related syndromes

Childhood syndromes
Typical HUS: Caused by Shiga toxin-producing Escherichia coli, typically E. coli O157:H7, or Shigella species.
Children present with abdominal pain and diarrhea, typically bloody, and acute kidney injury. Ninety percent of
childhood HUS.

Atypical HUS: Acute kidney injury without preceding diarrhea. Some cases may be familial, caused by
mutation of genes involved in complement regulation. Ten percent of childhood HUS.

Hereditary TTP (Upshaw-Schulman syndrome). Caused by mutation(s) in the ADAMTS13 gene.

Acquired autoimmune TTP: Caused by autoantibody inhibition of ADAMTS 13 activity; rare in children.

Adult syndromes
Acquired autoimmune TTP: Caused by autoantibody inhibition of ADAMTS 13 activity.

Drug-induced thrombotic microangiopathy (DITMA)


Immune mediated

Quinine is the most common cause.

Dose-dependent toxicity

Cancer chemotherapy (mitomycin C, gemcitabine, possibly others)

Immunosuppressive agents (cyclosporine, tacrolimus, sirolimus)

Following bloody diarrhea caused by Shiga toxin-producing E. coli or Shigella species

Pregnancy or postpartum: May be indistinguishable from severe preeclampsia, eclampsia, and the HELLP
syndromes.

Hereditary TTP (Upshaw-Schulman syndrome) may present during adulthood, sometimes triggered by another
condition (eg, infection, pregnancy).

Autoimmune disorders
Systemic lupus erythematosus (SLE) can mimic all features of a thrombotic microangiopathy. Patients may have both
TTP caused by severe ADAMTS13 deficiency and SLE.

Refer to UpToDate content on the approach to the patient with suspected TTP or HUS and on specific
syndromes for further details.

TTP: thrombotic thrombocytopenic purpura; HUS: hemolytic uremic syndrome.

Graphic 69868 Version 10.0


Contributor Disclosures
Phyllis August, MD, MPH Nothing to disclose Charles J Lockwood, MD, MHCM Consultant/Advisory
Boards: Celula [Aneuploidy screening (No current products or drugs in the US)]. Paul M Palevsky,
MD Grant/Research/Clinical Trial Support: Spectral Medical [Sepsis (Endotoxin assay)]. Consultant/Advisory
Boards: Baxter [Dialysis (Hemodialysis equipment, peritoneal dialysis equipment and supplies, continuous
renal replacement therapy equipment and solutions)]; Stealth Biotherapeutics [AKI]. Alice M Sheridan,
MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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