Acute kidney injury in pregnancy

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.

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'.)

EPIDEMIOLOGY — AKI during pregnancy is uncommon in resource-abundant settings. The true incidence is difficult to estimate because of varying diagnostic criteria. Most reviews estimate that, in countries with adequate antenatal care, 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 in settings where illegal abortions are performed [4,5].

ETIOLOGY ACCORDING TO CLINICAL PRESENTATION

Volume depletion — Volume depletion, typically due to severe vomiting (ie, hyperemesis gravidarum), is a common cause of prerenal AKI early in pregnancy (<20 weeks). (See "Nausea and vomiting of pregnancy: Clinical findings and evaluation".)

Infection

●Sepsis unrelated to pregnancy – Severe viral (eg, influenza) or bacterial infections that occur in the general population and result in sepsis-associated acute tubular necrosis (ATN) are a common cause of AKI early in pregnancy (<20 weeks). In later pregnancy, sepsis is less common than other causes of AKI. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

●Septic abortion – Septic abortion leading to sepsis-associated ATN is another common cause of AKI early in pregnancy (<20 weeks). (See "Septic abortion: Clinical presentation and management".)

●Acute pyelonephritis – The incidence of pyelonephritis increases in the second and third semesters of pregnancy, and severe pyelonephritis can lead to sepsis-associated ATN [6]. Rarely, suppurative pyelonephritis may directly cause AKI in the absence of sepsis or other kidney insults [7,8].

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

Obstetric catastrophe — Catastrophic obstetric emergencies leading to massive hemorrhage and/or cardiovascular collapse (eg, placenta previa, placental abruption, prolonged intrauterine fetal death, or amniotic fluid embolism) may cause ischemic ATN or renal cortical necrosis, a severe and often irreversible form of ischemic ATN [9]. Renal cortical necrosis is now generally considered quite rare in resource-abundant countries and is responsible for only 1 to 2 percent of all cases of AKI in pregnancy [9,10]. However, 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 [2,11-14]. (See "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality" and "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences" and "Amniotic fluid embolism".)

Patients with renal 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 [11,12]. The triad of oliguria/anuria, gross hematuria, and flank pain is unusual in the other causes of AKI in pregnancy.

Both disseminated intravascular coagulation (DIC) and severe kidney 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 [15].

Microangiopathic hemolysis and thrombocytopenia — AKI in late pregnancy, especially when associated with varying degrees of microangiopathic hemolysis and thrombocytopenia, suggests a possible diagnosis of preeclampsia with severe features, with or without HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), thrombotic thrombocytopenic purpura (TTP), complement-mediated thrombotic microangiopathy (CM-TMA), or acute fatty liver of pregnancy (AFLP). There is considerable overlap in symptoms and laboratory abnormalities among these disorders, which can make distinguishing between them difficult (table 1). (See 'Subsequent evaluation' below.)

Preeclampsia with severe features/HELLP — Preeclampsia is the most common cause of AKI during pregnancy. However, most patients with preeclampsia do not develop AKI [9,16]. Preeclampsia may cause AKI directly, or indirectly by leading to complications associated with ATN (eg, placental abruption). Preeclampsia occurs in 3 to 5 percent of all pregnancies; the risk is increased in those with hypertension, diabetes, or chronic kidney disease (CKD) from any cause [17]. (See "Preeclampsia: Clinical features and diagnosis", section on 'Risk factors'.)

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 individual (table 2). Patients with preeclampsia who have AKI (and/or other indicators of severity) meet criteria for the diagnosis of "preeclampsia with severe features" (table 3). The clinical features of preeclampsia are extensively discussed elsewhere. (See "Preeclampsia: Clinical features and diagnosis", section on 'Clinical presentation'.)

The frequency and severity of preeclampsia-associated AKI vary according to the presence or absence of the HELLP syndrome (see "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)", section on 'Laboratory criteria for diagnosis'):

●AKI is more common and severe when preeclampsia is accompanied by HELLP syndrome [9]. Some studies suggest that AKI occurs in 3 to 15 percent of cases of preeclampsia associated with HELLP [18-20]. In a retrospective study of 72 patients with preeclampsia and AKI admitted to an obstetric intensive care unit, 15 had severe AKI (defined in the study as a serum creatinine greater than approximately 7 mg/dL); of these 15 patients, 11 had HELLP [18]. In the remaining four patients without HELLP, all had additional factors that contributed to their AKI (eg, abruptio placentae).

●By contrast, AKI appears to be much less common in patients with preeclampsia who do not have HELLP syndrome [9]. However, the frequency of AKI in this population is difficult to quantify; published studies reporting the incidence of AKI in preeclampsia generally have not stratified patients by the presence or absence of HELLP features [16].

Rarely, preeclampsia with AKI is first diagnosed in the postpartum period, without documentation of antepartum hypertension and proteinuria [21,22]. Preeclampsia with AKI that is first observed in the postpartum period should be distinguished from other microangiopathic disorders, particularly CM-TMA. (See 'Diagnostic evaluation' below.)

Thrombotic thrombocytopenic purpura or complement-mediated thrombotic microangiopathy — Pregnancy is a well-recognized trigger for both the onset or relapse of TTP and CM-TMA [9,23-28]. Presenting features of TTP and CM-TMA include thrombocytopenia and microangiopathic hemolytic anemia without another apparent cause and, in many patients, AKI and/or neurologic abnormalities (table 4) [29,30].

TTP and CM-TMA are both characterized by the presence of microthrombi of fibrin and/or platelets in multiple organ systems, particularly the kidney and the brain. However, these thrombotic microangiopathies differ in their pathophysiology and frequently differ by timing of onset and/or degree of kidney involvement (table 1). These differences are summarized as follows:

●Pathophysiology – TTP is caused by an acquired or constitutional deficiency of activity of ADAMTS13, a Von Willebrand factor-processing protein [31]. CM-TMA is caused by uncontrolled complement activation, usually in association with mutations in genes that encode complement-regulatory proteins [23-25,32]. The frequency at which mutations in the genes encoding complement-regulating proteins are detected in pregnancy-associated CM-TMA has varied. In one study of 87 patients, mutations were detected among 56 percent [33]. In another study of 21 patients, mutations were identified among 86 percent [25]. The pathophysiology of TTP and CM-TMA are discussed in detail elsewhere. (See "Pathophysiology of TTP and other primary thrombotic microangiopathies (TMAs)".)

●Timing of onset – TTP in pregnancy occurs predominantly in the second and third trimesters [25]. ADAMTS13 levels tend to fall during the last two trimesters of pregnancy, which could contribute to the time course of development of TTP [26,34-36]. By contrast, pregnancy-associated CM-TMA more commonly occurs postpartum [25,33]. In one case series, 76 percent of pregnancy-associated CM-TMA occurred in the immediate postpartum period [33]. Postpartum CM-TMA may follow a normal pregnancy or be preceded by findings indistinguishable from preeclampsia [21,22,37].

Among individuals with mutations in complement-regulatory genes, pregnancy-associated CM-TMA is more likely to occur during the second pregnancy, despite history of a normal first pregnancy [25].

●Frequency and severity of AKI – AKI may occur in either TTP or CM-TMA, though it is more common and generally more severe among patients with CM-TMA. In one study, 4 out of 35 (11 percent) of patients with pregnancy-associated TTP had AKI [38]. By contrast, in a study of 87 patients with pregnancy-associated CM-TMA, over half required dialysis at or shortly after diagnosis [33].

Acute fatty liver of pregnancy — AFLP is rare but is associated with AKI in up to 60 percent of cases [2,39]. The pathogenesis of AFLP is discussed elsewhere. (See "Acute fatty liver of pregnancy", section on 'Pathogenesis'.)

Patients with AFLP present in the third trimester, typically with nonspecific symptoms such as loss of appetite, nausea, vomiting, and abdominal pain, and often with clinical signs consistent with preeclampsia (ie, hypertension and thrombocytopenia). Signs and symptoms of acute liver failure, including jaundice, ascites, encephalopathy, and hypoglycemia, rapidly develop [40,41]. Microangiopathic hemolysis is associated with DIC. The clinical features of AFLP are extensively discussed elsewhere. (See "Acute fatty liver of pregnancy", section on 'Patient presentation'.)

Nephritic syndrome (acute glomerulonephritis) — The nephritic syndrome (ie, acute glomerulonephritis) is uncommon in pregnancy. Patients typically present with hematuria (often with dysmorphic red blood cells and/or red blood cell casts), proteinuria (which can sometimes be in the nephrotic range), hypertension, and varying degrees of kidney function impairment. Glomerulonephritis may be due to systemic lupus erythematosus (SLE) or to a variety of other diseases (eg, antineutrophil cytoplasmic autoantibodies [ANCA]-associated vasculitis). AKI in pregnancy may be the first manifestation of SLE or may represent a flare of preexisting disease [42].

In a prospective cohort study of 71 pregnancies in patients with a history of lupus nephritis, a lupus nephritis flare occurred in 20 percent of patients [43]. The clinical features of lupus nephritis are detailed elsewhere. (See "Lupus nephritis: Diagnosis and classification", section on 'Clinical features'.)

Kidney stones — Urinary tract obstruction is rare in pregnancy and is almost always caused by kidney stones, though cases of obstruction due to expanding uterine fibroids have been reported [44]. AKI due to nephrolithiasis usually occurs in the setting of an obstructed unilateral kidney or an infected stone leading to sepsis-associated AKI [45,46]. The development of a symptomatic stone during pregnancy occurs in approximately 1 in every 500 to 3000 pregnancies [47-49].

Patients with kidney stones usually present in the second or third trimester (approximately 20 percent in the first trimester) with acute flank pain (90 percent), which often radiates to the groin or lower abdomen. Hematuria is present in 75 to 95 percent, one-third of whom have gross hematuria, and approximately 40 percent will have pyuria [47,48]. These presenting symptoms are similar to those in nonpregnant patients. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Symptomatic stones'.)

DIAGNOSTIC EVALUATION

Identification of acute kidney injury — AKI is defined by the abrupt loss of kidney function and is generally identified by laboratory evaluation showing an increased serum creatinine above the patient's usual baseline. Although several consensus definitions of AKI have been developed for use in the general population (table 5), none have been validated in pregnancy.

In clinical practice, we avoid strict adherence to these consensus criteria for AKI since doing so may delay or prevent the detection of AKI that occurs 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 that in 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.

Initial evaluation — Patients with AKI who are pregnant should be thoroughly evaluated for causes of AKI unrelated to pregnancy, as detailed elsewhere. (See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting" and "Evaluation of acute kidney injury among hospitalized adult patients".)

We take a systematic approach to the evaluation of pregnant patients with AKI. Even if the cause of AKI seems obvious, skipping steps in the diagnostic evaluation risks missing important causes of or contributors to AKI. Our initial diagnostic approach to patients with AKI during pregnancy is outlined below.

●Medical history and physical examination – A review of the medical history and physical examination findings often provides important clues to the etiology of AKI. Examples include the following:

•A history of systemic lupus erythematosus (SLE) or evidence of proteinuria and/or hematuria prior to pregnancy may suggest worsening of an underlying glomerulonephritis.

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

•A review of medications may identify potential nephrotoxins. For example, nonsteroidal antiinflammatory drugs (NSAIDs) are routinely used for postpartum analgesia, particularly after cesarean delivery. 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".)

•Physical examination may identify signs of volume depletion, suggesting prerenal AKI, or skin and joint findings suggestive of a SLE disease flare. (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'History and physical examination'.)

●Laboratory tests – In addition to a careful review of the medical history and physical examination, we obtain the following initial 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 – We obtain a kidney ultrasound to rule out urinary tract obstruction in most patients with AKI. The exception is when history and physical examination suggest prerenal AKI and the AKI rapidly corrects with the administration of volume and/or treatment of hypotension. (See 'Subsequent evaluation' below.)

Results of kidney imaging must be interpreted in the context of the physiologic changes of pregnancy. Relaxation of ureteral smooth muscle and pressure on the ureters by the gravid uterus often result in mild to moderate dilatation of the collecting systems [50,51]. This functional hydronephrosis, which tends to be more prominent on the right, is detectable by ultrasonography but is not usually associated with kidney dysfunction. Distinguishing the physiological hydronephrosis of pregnancy from pathological obstruction is discussed elsewhere. (See "Kidney stones in adults: Kidney stones during pregnancy", section on 'Diagnosis in pregnancy'.)

Subsequent evaluation — The subsequent diagnostic evaluation, including the need for additional testing, is guided by the clinical presentation and results of the initial evaluation.

●Volume depletion, infection, or obstetric catastrophe – Pregnant patients with AKI who have volume depletion, infection, or obstetric catastrophe usually have prerenal AKI or ATN.

•Prerenal AKI – The diagnosis of prerenal AKI is suggested by the history and physical examination (eg, severe vomiting and signs of volume depletion, as seen in hyperemesis gravidarum) and a urinalysis that is generally bland with minimal proteinuria. The diagnosis is confirmed when AKI rapidly corrects with the administration of volume and/or treatment of hypotension.

•ATN – A clinical diagnosis of ATN is usually made when the history and physical examination demonstrate a clear precipitant (eg, sepsis, hemorrhage, and/or cardiovascular collapse) and there is no evidence for another cause of AKI (eg, hematuria or urinary tract obstruction). A urinary sediment showing pigmented granular casts and/or renal tubular epithelial cells supports the diagnosis of ATN, but the absence of these classic urinary findings does not rule out the diagnosis. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

Kidney biopsy is usually not required to diagnose ATN and is generally reserved for patients who develop atypical features or who do not recover kidney function in the expected time frame (see 'Treatment and Outcome' below). Patients with a clinical diagnosis of ATN in the setting of obstetric catastrophe who have no recovery or incomplete recovery of kidney function after several weeks may have cortical necrosis. In such patients, cortical necrosis can be diagnosed by repeat ultrasonography or with computed tomography (CT) scanning, which demonstrate hypoechoic or hypodense areas in the renal cortex [11].

●Microangiopathic hemolysis and thrombocytopenia – Among patients who have hemolysis and thrombocytopenia, other tests are indicated to evaluate for TTP (ie, levels of ADAMTS13, a Von Willebrand factor-processing protein) and CM-TMA (ie, measurement of complement proteins); unfortunately, the results of many of these diagnostic tests are not available in time to make crucial therapeutic decisions. (See "Thrombotic microangiopathies (TMAs) with acute kidney injury (AKI) in adults: CM-TMA and ST-HUS", section on 'Evaluation' and "Hereditary thrombotic thrombocytopenic purpura (hTTP)", section on 'Diagnostic evaluation'.)

Although there is considerable overlap in symptoms and laboratory abnormalities among preeclampsia with severe features/HELLP, TTP, CM-TMA, and AFLP, an accurate diagnosis is usually made by careful consideration of the clinical presentation in association with the pattern of laboratory abnormalities (table 1). Some useful distinguishing criteria are summarized below [21,22,37]:

•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 CM-TMA most commonly presents immediately postpartum.

-AFLP develops in the third trimester and resolves within one to two weeks postpartum [40].

-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 CM-TMA.

•Clinical and laboratory features

-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 CM-TMA.

-A prodrome of anorexia and nausea followed by jaundice, AKI, consumptive coagulopathy, and/or hypoglycemia due to liver dysfunction suggests AFLP. (See "Acute fatty liver of pregnancy", section on 'Diagnosis'.)

-Severe deficiencies of ADAMTS13 activity (ie, ≤10 percent) suggest TTP. By contrast, plasma levels of ADAMTS13 are only mildly or moderately reduced in patients with HELLP syndrome [52]. We do not use scoring systems (eg, the PLASMIC score) to predict the likelihood of severely reduced ADAMTS13, since such scores have not been validated in pregnancy.

Kidney biopsy is rarely, if ever, required to distinguish between preeclampsia with or without HELLP syndrome, AFLP, and TTP or CM-TMA and is usually not performed. 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 pregnant patients with well-controlled blood pressure and normal coagulation indices [53], but it is generally deferred until the postpartum period unless the results may change management prior to delivery. (See "The kidney biopsy", section on 'Contraindications'.)

●Nephritic syndrome (acute glomerulonephritis) – Patients presenting with features of the nephritic syndrome (see 'Nephritic syndrome (acute glomerulonephritis)' above) should be evaluated for glomerulonephritis with laboratory tests, including serum C3 and C4 complement levels, antinuclear antibodies (ANA), anti-double-stranded (ds)DNA antibodies, and antineutrophil cytoplasmic autoantibodies (ANCA). (See "Glomerular disease: Evaluation and differential diagnosis in adults", section on 'Evaluation of glomerulonephritis'.)

Several features distinguish acute glomerulonephritis from AKI due to preeclampsia. Patients with glomerulonephritis have an active urine sediment; by contrast, hematuria is not a common finding in preeclampsia. While hypertension is a typical feature of acute glomerulonephritis, it is not uniformly present. Patients with AKI due to preeclampsia almost always have hypertension. AKI with proteinuria in the first trimester or early second trimester (before 20 weeks) is usually due to acute glomerulonephritis.

In patients with SLE, low complement levels and increased titers of anti-dsDNA also are useful to distinguish lupus nephritis from preeclampsia. (See "Pregnancy in women with systemic lupus erythematosus", section on 'Preeclampsia versus lupus nephritis'.)

In many cases of glomerulonephritis, a kidney biopsy is necessary to obtain a definitive diagnosis. However, kidney biopsy in pregnancy is generally reserved for patients in whom a definitive diagnosis has significant implications for immediate treatment. (See "The kidney biopsy", section on 'Contraindications'.)

●Obstructive uropathy – In pregnant patients with AKI who have ultrasound findings consistent with urinary tract obstruction, additional imaging with magnetic resonance urography or low-dose CT is usually required for diagnosis and subsequent management. This is discussed in detail elsewhere. (See "Kidney stones in adults: Kidney stones during pregnancy", section on 'Diagnosis in pregnancy'.)

In patients with AKI and confirmed urinary tract obstruction, urgent urologic consultation should be obtained.

TREATMENT AND OUTCOME — Treatment is targeted to the specific cause of AKI. Although indications for urgent dialysis in pregnancy are the same as those in the general population (see "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose"), the decision to initiate dialysis electively in a pregnant patient often must be individualized. Barring urgent indications, or the impending development of such indications, early initiation of dialysis in the nonobstetric setting is typically avoided because it may be harmful and can delay recovery of kidney function. However, early initiation of dialysis in pregnancy may be considered with the aim of improving pregnancy outcomes, especially in situations where rapid recovery of kidney function is not expected and prolongation of pregnancy is desired. No high-quality data exist to guide the dialytic strategy in a pregnant patient with AKI; the putative benefits of aggressive dialysis in this setting are extrapolated from data demonstrating that advanced nondialysis chronic kidney disease (CKD) is associated with a variety of pregnancy complications and that more intensive dialysis improves pregnancy outcomes in patients with end-stage kidney disease (ESKD). (See "Pregnancy and contraception in patients with nondialysis chronic kidney disease", section on 'Indications to initiate hemodialysis' and "Pregnancy in patients on dialysis".)

Treatment and kidney outcomes of selected AKI etiologies are outlined below:

●Preeclampsia with severe features/HELLP – Preeclampsia with severe features with or without HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is an indication for urgent delivery (see "Preeclampsia: Antepartum management and timing of delivery").

Additional management considerations for the HELLP variant of preeclampsia are discussed elsewhere. (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)", section on 'Management'.)

The renal and extrarenal abnormalities of preeclampsia typically begin to resolve spontaneously within two to three days postpartum, and complete recovery of glomerular filtration rate (GFR) occurs within eight weeks postpartum [54,55]. 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 [56]. Individuals who develop preeclampsia may be at increased risk of developing 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'.)

●ATN and renal cortical necrosis – The treatment of acute tubular necrosis (ATN) is supportive; no specific therapy has been shown to be effective. (See "Possible prevention and therapy of ischemic acute tubular necrosis", section on 'Treatment'.)

Kidney function in patients with ATN typically takes between one and three weeks to recover. However, patients with preexisting CKD or who experience repeated hemodynamic or nephrotoxic insults may take months to recover kidney function, and/or may have incomplete recovery due to irreversible injury.

Many patients with renal cortical necrosis require dialysis and do not recover kidney function [10,57]. Approximately 20 to 40 percent of patients with renal cortical necrosis have partial kidney recovery with a creatinine clearance that stabilizes between 15 and 50 mL/min [12].

●Thrombotic thrombocytopenic purpura – Plasma exchange is an important component of treatment of AKI due to pregnancy-associated TTP [33]. The treatment of pregnancy-associated TTP is discussed in detail elsewhere. (See "Thrombocytopenia in pregnancy", section on 'Management decisions' and "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 (hTTP)", section on 'Management of pregnancy'.)

The development of advanced CKD is uncommon in patients with TTP, even after an episode of AKI [58].

●Complement-mediated thrombotic microangiopathy – Anticomplement therapy (eg, eculizumab) is indicated for treatment of CM-TMA [9,59]. The treatment of pregnancy-associated CM-TMA is discussed in detail elsewhere. (See "Thrombocytopenia in pregnancy", section on 'Management decisions'.)

The kidney prognosis of patients with pregnancy-associated CM-TMA who are not treated with anticomplement therapy is poor. In one study of 87 patients with pregnancy-associated CM-TMA, only four received eculizumab [33]. Over a mean follow-up of seven years, 53 percent of patients developed ESKD and an additional 19 percent had CKD.

Patients with CM-TMA who are treated with anticomplement therapy appear to have an improved prognosis over historical controls, with a considerably lower rate of progression to ESKD than would be expected based on the natural history of the disease [60,61]. Registry data suggest that the improved kidney outcomes associated with eculizumab are similar in pregnancy-associated CM-TMA and non-pregnancy-associated CM-TMA [62].

●Acute fatty liver of pregnancy – Therapy consists of treatment of disseminated intravascular coagulation (DIC) and immediate delivery of the fetus [2,40]. (See "Acute fatty liver of pregnancy", section on 'Initial management'.)

Long-term maternal consequences of AFLP are uncertain. The disease is rare, and most studies have not followed patients beyond the immediate postpartum phase of the illness [63].

●Lupus nephritis – The treatment of lupus nephritis in pregnancy is discussed elsewhere. (See "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis", section on 'Pregnant patients'.)

●Obstructive uropathy/kidney stones – Obstructive AKI usually resolves with relief of obstruction. Procedures to relieve obstruction, such as ureteral stents or nephrostomy tubes, 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 [64]. The surgical management of kidney stones in pregnancy is discussed in detail elsewhere. (See "Kidney stones in adults: Kidney stones during pregnancy", section on 'Surgical management'.)

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SUMMARY AND RECOMMENDATIONS

●Epidemiology – Pregnancy-related acute kidney injury (AKI) is uncommon in resource-abundant settings. 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.)

●Etiology according to clinical presentation – The causes of AKI in pregnancy are associated with a variety of clinical presentations as follows (see 'Etiology according to clinical presentation' above):

•Volume depletion – Volume depletion, typically due to severe vomiting (ie, hyperemesis gravidarum), is a common cause of prerenal AKI early in pregnancy (<20 weeks).

•Infection – Severe infections that occur in the general population or septic abortion may lead to sepsis-associated acute tubular necrosis (ATN), which is another common cause of AKI early in pregnancy. The incidence of pyelonephritis increases in the second and third semester of pregnancy, and severe pyelonephritis also can lead to sepsis-associated ATN.

•Obstetric catastrophe – Catastrophic obstetric emergencies leading to massive hemorrhage and/or cardiovascular collapse (eg, placenta previa, placental abruption, prolonged intrauterine fetal death, or amniotic fluid embolism) may cause ischemic ATN or renal cortical necrosis, a severe and often irreversible form of ischemic ATN. Patients with cortical necrosis present with the abrupt onset of oliguria or anuria, frequently accompanied by gross hematuria and flank pain.

•Microangiopathic hemolysis and thrombocytopenia – Preeclampsia, with or without HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), is the most common cause of AKI during pregnancy and generally occurs after 20 weeks of gestation. Other causes of AKI associated with microangiopathic hemolysis and thrombocytopenia include thrombotic thrombocytopenic purpura (TTP), complement-mediated thrombotic microangiopathy (CM-TMA), and acute fatty liver of pregnancy (AFLP) (table 1).

•Nephritic syndrome (acute glomerulonephritis) – The nephritic syndrome is uncommon in pregnancy. Patients typically present with hematuria (often with dysmorphic red blood cells and/or red blood cell casts), proteinuria (which can sometimes be in the nephrotic range), hypertension, and varying degrees of kidney function impairment.

•Kidney stones – Urinary tract obstruction is rare in pregnancy and is almost always caused by kidney stones. AKI due to nephrolithiasis usually occurs in the setting of an obstructed unilateral kidney or an infected stone leading to sepsis-associated AKI.

●Initial evaluation – The initial evaluation of pregnancy-associated AKI includes a history, physical examination, and the following tests (see 'Initial evaluation' above):

•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

●Subsequent evaluation – The subsequent diagnostic evaluation, including the need for additional testing, is guided by the clinical presentation and results of the initial evaluation. A kidney biopsy is rarely performed in the obstetric setting. Although it may be difficult to distinguish between preeclampsia with or without HELLP syndrome, TTP, CM-TMA, and AFLP because of the overlap in symptoms and laboratory abnormalities, an accurate diagnosis is usually made based upon clinical features (table 1). (See 'Subsequent evaluation' above.)

●Treatment – The specific treatment for pregnancy-associated AKI depends on the underlying etiology. Although indications for urgent dialysis in pregnancy are the same as those in the general population, the decision to initiate dialysis electively in a pregnant patient often must be individualized. (See 'Treatment and Outcome' above.)

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