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 adult patients with subacute kidney injury in an outpatient setting", section on 'Major causes and pathogenesis of kidney disease'.)
Nephrolithiasis during pregnancy is discussed elsewhere. (See "Kidney stones in adults: Kidney stones 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 adult patients 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 "Maternal adaptations to pregnancy: Renal and urinary tract physiology", section on 'Renal plasma flow and glomerular filtration rate disconnect in late gestation'). 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 kidney replacement therapy [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 "Nausea and vomiting of pregnancy: Clinical findings and evaluation", section on 'Evaluation')
●Acute tubular necrosis (ATN) resulting from a septic abortion (see "Unsafe abortion", section on 'Morbidity and mortality')
●AKI associated with either viral (eg, influenza) or bacterial infection and/or sepsis
Several disorders can lead to AKI later in pregnancy or postpartum [1,2]. These include:
●Severe preeclampsia (see "Preeclampsia: Clinical features and diagnosis")
●Severe preeclampsia with HELLP syndrome (see "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)")
●Thrombotic microangiopathy including thrombocytopenic purpura (TTP; acquired or hereditary) or complement-mediated thrombotic microangiopathy (C-TMA) (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 "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality" and "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences" and "Amniotic fluid embolism")
●AKI associated with nonsteroidal antiinflammatory drugs (NSAIDs)
In addition to these conditions, acute pyelonephritis and, less commonly, urinary tract obstruction have been associated with AKI in pregnant women. Acute tubulointerstitial nephritis associated with medications and AKI associated with acute glomerulonephritis are other uncommon etiologies of AKI in pregnancy. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Acute pyelonephritis' and "Clinical manifestations and diagnosis of acute interstitial nephritis", section on 'Drugs' and "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting", section on 'Intrinsic glomerular disease'.)
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). Pregnancy-associated C-TMA usually develops in the postpartum period, although it may be preceded by antepartum preeclampsia in some patients. AKI secondary to ATN may develop due to hemodynamic stress associated with either hemorrhage or sepsis.
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 by no more than 30 to 40 percent, which results in small increases in the serum creatinine [7]. AKI requiring kidney replacement therapy (KRT) 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. In a prospective observational study of 1547 women admitted for preeclampsia in South Africa, 237 (15 percent) met Kidney Disease: Improving Global Outcomes (KDIGO) criteria for the diagnosis of AKI [8]. Among those with AKI, 45 percent had stage 1 AKI, 28 percent had stage 2 AKI, and 27 percent had stage 3 AKI. Compared with patients with preeclampsia without AKI, those with AKI had a higher risk of maternal death (relative risk [RR] 4.3, 95% CI 1.6-11.4) and stillbirth (RR 2.2, 95% CI 1.8-2.8). Hypertension in a previous pregnancy was the strongest predictor of stage 2 or 3 AKI (odds ratio 2.24, 95% CI 1.21-4.17).
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 (hemolysis, elevated liver enzymes, and low platelets)", section on 'Laboratory criteria for diagnosis'.)
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 [9-11]. 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 [12,13]. Preeclampsia that is first observed in the postpartum period should be distinguished from microangiopathic disorders, particularly C-TMA. This issue is discussed below. (See 'Diagnostic approach and differential diagnosis' below.)
Severe preeclampsia is an indication for urgent delivery (see "Preeclampsia: Antepartum management and timing of delivery"). 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 [14,15]. Occasionally, if proteinuria is severe, it may take several months to resolve completely. Moderately increased albuminuria (ie, between 30 and 300 mg/day [20 to 200 mcg/min], formerly called "microalbuminuria") may persist [16]. Women who develop preeclampsia may be at increased risk of developing end-stage kidney disease (ESKD) later in life, but the absolute risk is small. This issue is discussed elsewhere. (See "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Long-term maternal risks of pregnancy-associated hypertension'.)
The treatment of the HELLP variant of preeclampsia is discussed elsewhere. (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)", section on 'Management of patients presenting before delivery'.)
Thrombotic thrombocytopenic purpura or hemolytic uremic syndrome — TTP and C-TMA 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 [17,18]. (See "Diagnosis of immune TTP" and "Thrombocytopenia in pregnancy", section on 'Thrombotic microangiopathy (TMA)'.)
Pregnancy may trigger either TTP or C-TMA [19-21].
TTP is caused by an acquired or constitutional deficiency of activity of ADAMTS13, a Von Willebrand factor-processing protein [22]. Pregnancy has been shown to induce the onset or relapse of ADAMTS13 deficiency-related TTP [7]. (See "Immune 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 'Management of pregnancy'.)
C-TMA is caused by mutations in genes that encode complement-regulatory proteins, which result in uncontrolled complement activation [19-21,23]. Pregnancy is a well-recognized trigger for episodes of C-TMA in patients with these mutations. The frequency at which mutations in the genes encoding complement-regulating proteins are detected has varied in the literature. In one study of 87 patients who had pregnancy-associated C-TMA (76 percent postpartum), mutations were detected among 56 percent [24]. In another study of 21 patients, mutations were identified among 86 percent [21]. (See "Complement-mediated hemolytic uremic syndrome in children".)
TTP and C-TMA differ in the timing of onset. TTP associated with ADAMTS13 deficiency occurs predominantly in the second and third trimesters [21]. ADAMTS13 levels tend to fall during the last two trimesters of pregnancy, which could contribute to the time course of development of TTP [25-28]. Pregnancy-associated C-TMA more commonly occurs in the postpartum period [21,24]. Among women with mutations in complement-regulatory genes, pregnancy-associated C-TMA is more likely to occur during the second pregnancy and recur in subsequent pregnancies, despite history of a normal first pregnancy.
AKI may occur in either pregnancy-associated TTP or C-TMA, though it is more common among patients with C-TMA. In the study cited above of 87 patients with pregnancy-associated C-TMA, over a mean follow-up of seven years, 53 percent of patients developed end-stage kidney disease and an additional 19 percent had CKD [24].
Postpartum C-TMA may follow a normal pregnancy or be preceded by findings indistinguishable from preeclampsia [12,13,29].
TTP or C-TMA that initially occurs in nonpregnant women may relapse during a subsequent pregnancy, and recurrent TTP or C-TMA may develop during successive pregnancies [21,25,30,31]. Most subsequent pregnancies with TTP are uncomplicated, and most children survive [21,32]. (See "Immune TTP: Initial treatment".)
The diagnosis is generally made by clinical features. Kidney 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 kidney 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 C-TMA is discussed elsewhere (see "Thrombocytopenia in pregnancy", section on 'Management decisions'). Plasma exchange is an important component of treatment of AKI due to pregnancy-associated TTP, but may not be effective in C-TMA [24]. Emerging evidence from case reports and case series suggests that eculizumab, a monoclonal humanized immunoglobulin G (IgG) that inhibits complement activation, may be effective in treating pregnancy-associated C-TMA [7,33]. Since C-TMA usually presents in the postpartum period, issues related to fetal toxicity due to eculizumab are not a concern. We are not aware of any fetal toxicity associated with antepartum use of eculizumab. (See "Complement-mediated hemolytic uremic syndrome in children", section on 'Treatment'.)
Treatment of AKI is supportive (see 'Treatment' below). 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. If elevated liver enzymes are present, the diagnosis is more likely to be AKI due to HELLP syndrome.
Most patients requiring dialysis, however, are postpartum, and considerations for KRT are similar to nonpregnant adults with AKI (see "Kidney 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 [2,34].
The pathogenesis of AFLP is discussed elsewhere. (See "Acute fatty liver of pregnancy".)
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 [35]. (See "Acute fatty liver of pregnancy".)
The diagnosis should be suspected based on clinical features, such as loss of appetite, nausea, and vomiting in the third trimester, with confirmatory laboratory features [36]. 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 [2,35] (see "Acute fatty liver of pregnancy", section on 'Laboratory, imaging, and histologic findings'). The laboratory abnormalities frequently begin to improve within one to two days after delivery [35].
Renal cortical necrosis — Renal cortical necrosis used to be an important cause of AKI and, when present, is usually 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 resource-abundant 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 [2,37-40]. 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 resource-abundant countries [41]. 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. However, a randomized, controlled trial including over 20,000 participants showed no difference in AKI between participants assigned to tranexamic acid versus placebo [42]. (See "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Administer tranexamic acid'.)
Both 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 [43].
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 [37,38]. The triad of oliguria/anuria, gross hematuria, and flank pain is unusual in the other causes of kidney 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 [37].
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 [38].
Acute pyelonephritis — Asymptomatic bacteriuria occurs in 2 to 15 percent of pregnant patients and is a risk factor for development of symptomatic urinary tract infection, including pyelonephritis [44]. Pyelonephritis is usually characterized by dysuria, flank pain, nausea, and fever. Although kidney function is generally well maintained during episodes of acute pyelonephritis (in the absence of septicemia or hypotension), pregnant women with pyelonephritis are at increased risk for AKI [2,45]. 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 [46]. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Acute pyelonephritis'.)
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'.)
Kidney 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 [47,48]. (See "Maternal adaptations to pregnancy: Renal and urinary tract physiology".)
This functional hydronephrosis, which tends to be more prominent on the right, is detectable by ultrasonography but is not usually associated with kidney dysfunction.
Nephrolithiasis and renal colic are not uncommon during pregnancy, with some estimates of incidence of 1 in 200 to 1 in 500 pregnant patients [49]. Although most cases are managed conservatively, obstructive nephropathy may rarely occur and result in the need for procedures to relieve obstruction, such as ureteral stents or nephrostomy tubes. These procedures are often complicated in pregnancy due to the need for frequent exchanges and the possibility of infection of the inserted stent or nephrostomy tube. In addition, such procedures can also lead to obstetric complications such as preterm labor [50]. (See "Kidney stones in adults: Kidney stones during pregnancy".)
Occasionally, obstruction of the ureters by the uterus is sufficient to cause kidney failure [47]. The diagnosis can be established in some cases by the normalization of kidney function in the lateral recumbent position (which relieves pressure on the ureters by the uterus) and its recurrence when supine.
AKI due to urinary obstruction resulting from enlarged uterine fibroids during pregnancy has been reported [51].
Obstructive AKI usually resolves with relief of obstruction. This may be achieved by insertion of a ureteric stent or delivery of the fetus [48].
Postpartum AKI associated with nonsteroidal antiinflammatory 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".)
DIAGNOSTIC APPROACH AND DIFFERENTIAL DIAGNOSIS — AKI is generally identified by laboratory evaluation showing an increased serum creatinine above the patient’s usual baseline. (See 'Definition' above.)
Identification of the cause of AKI is important in order to administer appropriate therapy. The initial 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 adult patients 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 adult patients 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)
●Kidney 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 adult patients with subacute kidney injury in an outpatient setting", section on 'Major causes and pathogenesis of kidney disease' and "Glomerular disease: Evaluation and differential diagnosis in adults".)
Among patients who are determined to have hemolysis and thrombocytopenia, other tests are indicated to evaluate for thrombotic thrombocytopenic purpura (TTP) or complement-mediated thrombotic microangiopathy (C-TMA; such as measurement of complement proteins and ADAMTS13 levels). (See "Thrombotic microangiopathies (TMAs) with acute kidney injury (AKI) in adults: CM-TMA and ST-HUS" and "Diagnosis of immune TTP", section on 'PLASMIC score' and "Hereditary thrombotic thrombocytopenic purpura (TTP)", section on 'Diagnostic evaluation' and "Complement-mediated hemolytic uremic syndrome in children", 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 [37].
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. Kidney 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 symptoms suggestive of cystitis. Additional details regarding clinical manifestations and diagnosis of acute pyelonephritis are presented in detail elsewhere. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Acute pyelonephritis'.)
Obstructive uropathy associated with nephrolithiasis or obstetric causes can be evaluated by kidney ultrasound.
AKI in late pregnancy suggests a possible diagnosis of preeclampsia with or without HELLP syndrome, TTP or C-TMA, 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. Kidney biopsy is rarely, if ever, required to distinguish between preeclampsia with or without HELLP syndrome, AFLP, and TTP or C-TMA and is usually not performed, at least initially, because of thrombocytopenia. A kidney biopsy may be indicated for confirmation of diagnosis and for prognosis if AKI persists after resolution of the thrombocytopenia and hemolysis. A kidney biopsy can be performed safely by experienced operators in women with well-controlled blood pressure and normal coagulation indices [52]. Biopsy after week 32 is not recommended; among such patients, we defer biopsy until after delivery.
Some useful distinguishing criteria are summarized below [12,13,29]:
●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 hypercoagulable inflammatory disorders, such as the antiphospholipid antibody syndrome.
TTP is most common in the second and third trimesters, while C-TMA most commonly presents immediately postpartum. (See "Pathophysiology of 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 kidney failure suggest pregnancy-associated C-TMA. (See "Preeclampsia: Antepartum management and timing of delivery".)
●Clinical and laboratory features – Both the HELLP variant of severe preeclampsia, TTP, and C-TMA 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 C-TMA. 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 [53]. (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)", section on 'Patient presentation'.)
The thrombotic state in some patients with antiphospholipid antibodies may be indistinguishable from TTP or C-TMA. (See "Clinical manifestations of antiphospholipid syndrome".)
AFLP has many features of both TTP or C-TMA 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, AKI, 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. Preliminary evidence supports the use of eculizumab for complement-mediated thrombotic microangiopathy (C-TMA). Dialysis should be initiated based on the usual criteria for patients in the nonobstetric setting and particularly if oliguria is present. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose" and "Overview of the management of acute kidney injury (AKI) in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Acute kidney injury (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 pre-kidney disease due to hyperemesis gravidarum and acute tubular necrosis (ATN) resulting from a septic abortion or other bacterial or viral infections.
Causes of AKI in late pregnancy (after 20 weeks) include preeclampsia, thrombotic thrombocytopenic purpura (TTP), complement-mediated thrombotic microangiopathy (C-TMA), acute fatty liver of pregnancy (AFLP), ATN or acute cortical necrosis, acute pyelonephritis, and, rarely, urinary tract obstruction. Nonsteroidal antiinflammatory 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 ratio; 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 kidney 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, C-TMA, and AFLP because of the overlap in symptoms and laboratory abnormalities. Preeclampsia/HELLP syndrome is much more common than other microangiopathic disorders. An accurate diagnosis is usually made based upon clinical features. A kidney 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 kidney function, although moderately increased albuminuria (formerly called "microalbuminuria") may persist. (See 'Preeclampsia with or without HELLP' above.)
•TTP-associated AKI is primarily treated with plasma exchange, and C-TMA may be treated with plasma exchange, and possibly, eculizumab. (See "Immune 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 (AKI) in adults" and "Kidney 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 acknowledge James N George, MD, who contributed to earlier versions of this topic review.
