Acute kidney injury in pregnancy


Pregnancy-related acute kidney injury, acute renal failure in pregnancy

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Related Conditions

Acute kidney injury

Acute renal failure,

Hypertensive disorders of pregnancy


1. Description of the problem

Pregnancy-related acute kidney injury (PR-AKI) is acute kidney injury occurring during pregnancy, labor and delivery, and/or the postpartum period. The two categories are:

  • diseases or conditions that are specific and unique to pregnancy

  • diseases or conditions that happen to coincide with pregnancy (i.e., not pregnancy-specific)

Obstetrical AKI appears to be increasing in the United States which is partly attributable to increases in chronic hypertension and chronic kidney disease among pregnant women. Proper management of PR-AKI is challenging because (i) both maternal and fetal health must be considered and (ii) the cardiovascular and renal adaptations of pregnancy add to the complexity of diagnosis and management. A multi-disciplinary team is often needed to optimize all aspects of the pregnant woman’s care.

Clinical features

AKI is a clinical diagnosis based on the abrupt deterioration in kidney function. Despite efforts to standardize the definition in the general literature, AKI has been variably defined during pregnancy, ranging from serum creatinine levels of greater than 0.8 mg/dL or doubling of the serum creatinine to dialysis requirement.

Key management points

Management of PR-AKI can be complex for the following reasons:

  • There are two patients to consider, the mother and her fetus.

  • Renal and cardiovascular adaptations of pregnancy affect diagnosis and management.

  • A multi-disciplinary team approach is warranted (including specialists in critical care medicine, maternal-fetal medicine/high-risk obstetrics, nephrology, and neonatology).

Key management points are:

  • Stabilize the patient

  • Treat the underlying cause

  • Prevent progression of kidney damage

  • Maintain supportive care

  • Optimize fetal health

2. Emergency Management

Key steps in the emergency management of PR-AKI include:

  • Assess and restore hemodynamic stability (this overlaps with #2 and #3).

  • Identify and treat the underlying cause of AKI.

  • Prevent progression of kidney damage.

  • Maintain supportive care.

  • Maternal health takes priority, but fetal health should also be optimized.

General principles in the management of PR-AKI:

1. Stabilize the patient – this includes a basic assessment of airway, breathing, and circulation.

2. Identify and treat the underlying cause of AKI

  • The most common cause of PR-AKI is reduced renal perfusion. In most cases of pregnancy-specific causes of AKI, the cause of the renal injury is readily apparent, such as obstetric hemorrhage. The fundamental treatment in such cases is to stop the ongoing bleeding. Specific treatments are discussed in the following sections by underlying etiology.

3. Prevent progression of kidney damage

  • Maintaining adequate renal perfusion to limit ongoing damage and reverse any pre-ischemic changes is one of the most important principles in the management of PR-AKI. Volume resuscitation should be accomplished with intravenous crystalloid or colloid solutions as well as blood and blood products as indicated. Volume status should be monitored clinically, with close attention to urine output and pulmonary function. Invasive hemodynamic monitoring in an ICU setting is often warranted.

  • All nephrotoxic medications should be stopped or the dose adjusted to prevent further renal damage.

  • Pharmacologic therapies to prevent progression of renal decline are largely secondary. Vasoactive and diuretic medications may affect fetal well-being by reducing uterine blood flow and placental perfusion.

  • Post-renal causes of progressive renal injury such as obstruction of the urinary tract by the pregnant uterus can be relieved by ureteral stents, percutaneous nephrostomy, or delivery, if indicated.

4. Maintain supportive care

  • Hyperkalemia – should be promptly corrected using glucose/insulin or potassium-binding resins such as polystyrene sulfonate.

  • Metabolic acidosis – Intravenous bicarbonate can be used for acute correction of acidosis while the underlying cause is being treated. Of note, the physiologic respiratory alkalosis must be taken in account when addressing acid-base status in a pregnant woman.

  • Anemia – acute treatment is with red blood cell transfusion. Exogenous erythropoietin may be considered for chronic anemia.

  • Renal replacement therapy/dialysis – Indications for renal replacment therapy in pregnancy are similar to those in the nonpregnant patient:

    volume overload

    hyperkalemia refractive to medical management

    metabolic acidosis

    symptomatic uremia.

Hemodialysis is generally used in the acute setting. Recommendations in pregnancy include: increase in dialysis time and frequency, keeping serum urea <45-60 mg/dL, and minimizing fluid shifts and hypotension, which can affect fetal well-being. Renal replacement therapy is often short term in PR-AKI until there is recovery of renal function.

5. Optimize fetal well-being

  • In general, maternal health takes priority; however, the fetal condition should be optimized whenever possible.

  • Fetal well-being and neonatal outcomes are closely linked to maternal status. Adequate blood flow to the uterus and feto-placental unit are key factors in preventing fetal compromise; as such, intravascular volume depletion should be avoided and hypotension treated promptly.

  • Fetal monitoring – the degree and type of fetal monitoring is based on gestational age. For viable pregnancies (greater than 23-24 weeks of pregnancy), fetal well-being should be assessed at least daily. Fetal heart rate monitoring (continuous or intermittent) and/or biophysical profile evaluation by ultrasound may be used depending on the clinical situation. If preterm delivery is indicated after 24 weeks but prior to 34 weeks, then antenatal glucocorticoids should be administered to reduce neonatal mortality and morbidity. Maternal-fetal medicine specialists and neonatologists should be closely involved if preterm delivery is a consideration.

3. Diagnosis

Renal adaptations start very early in pregnancy. These dramatic changes have implications for normal laboratory parameters that may affect diagnosis and management of AKI.

1. Anatomic changes

  • Increase in size and volume of kidneys – this is due to increases in blood volume and capacity of collecting system

  • Dilation of the collecting system – this is due to smooth muscle relaxation, an effect of pregnancy hormones. Hydronephrosis and hydroureter occur in 80% of women by the midtrimester of pregnancy.

  • Right-sided ureteral dilation is greater than left – due to gravid uterus that is rotated towards the right and the vascular plexus at the pelvic brim.

2. Physiologic changes (Table I)

Table I.
Lab parameter Change compared to non-pregnant state Normal values in pregnancy
Serum creatinine lower ~ 0.5 mg/dL (<0.9 mg/dL)
Blood urea nitrogen (BUN) lower ~9.0 mg/dL
Plasma uric acid lower 2.0-3.0 mg/dL
pCO2 lower 27-32 mmHg
pH higher 7.40-7.45
Serum bicarbonate lower 18-20 mEq
Creatinine clearance higher ~25% above baseline (>100 cc/min)
Urinary protein excretion variable to higher <300 mg/24 hours
Urinary glucose excretion variable to higher may be present
  • Increase in renal blood flow and glomerular filtration rate (GFR) – This occurs concomitantly with a marked decrease in systemic vascular resistance, increase in plasma volume, and increase in cardiac output. Renal plasma flow increases by 50-80% and GFR increases by 40-65% by the third trimester compared to non-pregnant levels. Laboratory parameters are affected by these changes, resulting in different normative values during pregnancy. Serum creatinine and BUN are lower during pregnancy. Thus, a serum creatinine of 0.9 or 1.0 mg/dL which may be normal in a non-pregnant adult, is not normal for a healthy, pregnant woman. Proteinuria and glucosuria are not uncommon.

  • Volume and sodium balance – Although GFR is increased, tubular reabsorption results in a net sodium retention of 900-950 mEq and total body water increases by 6-8L over the course of pregnancy.

  • Acid-base changes – Minute ventilation is increased in pregnancy, which results in a respiratory alkalosis (pCO2 is reduced by approximately 10 mmHg). There is a partial compensatory metabolic acidosis with increased excretion of bicarbonate by the kidneys. While these adaptations facilitate gas exchange across the placenta, they reduce acid-buffering capacity in the mother. These changes are important to understand, particularly in the ICU setting.

Diagnosing pregnancy-specific causes of AKI
1. Hypertensive disorders of pregnancy
  • Preeclampsia – affects 3-10% of pregnancies. Diagnosis is based on new-onset hypertension and proteinuria after 20 weeks’ gestation (see Table II for specific diagnostic criteria). In severe forms of the syndrome, maternal brain, lungs, kidneys, liver, and platelets as well as placental function and fetal well-being can be affected. Serial blood pressures, timed urine collection for protein excretion, creatinine, liver transaminases, and platelets are helpful in making the diagnosis and classifying severity (see Table II). Systemic features include increased peripheral vascular resistance, vasospasm, endothelial dysfunction, activation of coagulation and inflammatory pathways, and platelet aggregation leading to ischemia and multi-organ dysfunction, including AKI. Renal plasma flow and GFR are reduced by approximately 24% and 32% respectively with preeclampsia; however, the majority of women with preeclampsia do not develop AKI. On the other hand, preeclampsia and other hypertensive disorders of pregnancy are the most common cause of PR-AKI, with an incidence of 1.5-2%. Often, there is a superimposed insult such as hemorrhage or DIC in a preeclamptic woman, which can lead to acute intravascular volume depletion and AKI. Acute tubular necrosis is most commonly seen with preeclampsia-associated AKI. Short-term renal replacment therapy may be required. The precise cause of preeclampsia is unknown. Reduced placental perfusion leading to maternal vascular dysfunction is hypothesized.

  • Eclampsia – seizures in a women with preeclampsia, not attributable to other causes

  • HELLP – hemolysis, elevated liver enzymes, low platelets; considered a variant of preeclampsia

  • Acute fatty liver of pregnancy – less common than preeclampsia; characterized by rapid progression and fulminant hepatic failure. Presenting symptoms are nausea/vomiting, abdominal pain, and malaise. Laboratory abnormalities include elevated liver transaminases, hyperbilirubinemia, elevated ammonia, coagulation abnormalities, hypoglycemia, and modest elevations in creatinine. As with preeclampsia, superimposed insults can accelerate AKI.

  • Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) – These are not pregnancy-specific, but can present like preeclampsia, HELLP syndrome or acute fatty liver and be coincident with pregnancy. TTP/HUS is more common in women (70%) and in pregnancy (13%), with significant mortality and long-term morbidity, including kidney injury. Often an accurate diagnosis cannot be made until after delivery, when preeclampsia-spectrum disorders improve while TTP/HUS does not (Table III).

Table II.
Preeclampsia New onset of sustained increase in BP, systolic >=140 or diastolic >=90 mmHg (on at least 2 occasions, 4 hours apart) in a previously normotensive woman
Proteinuria of >=300 mg/24 h after 20 weeks, or protein/creatinine ratio >=0.3 or dipstick reading of 1+
In the absence of proteinuria, new onset hypertension with the new onset of any of the following:
-platelet count <100,000/μL
-renal insufficiency with serum creatinine greater than 1.1 mg/dL or a doubling of creatinine in the absence of other renal disease
-impaired liver function with liver transaminases elevated to twice normal
-pulmonary edema
-cerebral or visual symptoms
Severe features of preeclampsia BP >=160 mmHg systolic or >=110 mmHg diastolic on at least 2 occasions, 4 hours apart (unless antihypertensive therapy is iniated before that time)
-platelet count <100,000/μL
-progressive renal insufficiency with serum creatinine greater than 1.1 mg/dL, or a doubling of creatinine in the absence of other renal disease
-impaired liver function with liver transaminases elevated to twice normal
-pulmonary edema
-new onset cerebral or visual symptoms
Eclampsia Seizures in a preeclamptic woman, not attributable to other causes
HELLP syndrome Hemolysis, elevated liver enzymes, low platelets
May or may not occur with hypertension
Considered a variant of preeclampsia
Superimposed preeclampsia
(diagnosed in women with pre-pregnancy hypertension)
Sudden and sustained increase in BP with or without significant increase in proteinuria
New onset of proteinuria (>=300 mg/24 h)
Sudden increase in proteinuria or hypertension in a woman with previously well-controlled BP and stable proteinuria before 20 weeks
Low platelets, elevated liver transaminases, or a rapid decline in renal function
Diagnosis may be challenging; a high index of suspicion is warranted!
Table III.
  Preeclampsia or HELLP Acute fatty liver of pregnancy Thrombotic thrombocytopenic purpura Hemolytic uremic syndrome
Pregnancy-specific yes yes no no
Onset usually 3rd trimester usually 3rd trimester median 23 weeks often postpartum
Major/unique clinical manifestation hypertension and proteinuria nausea, vomiting, malaise neurologic symptoms renal dysfunction
Fever no no yes no
Purpura no no yes no
Hemolysis mild mild severe severe
Platelets variable (normal to low) variable (normal to low) low variable (normal to low)
Coagulation studies variable abnormal normal normal
Hypoglycemia no yes no no
Other none some association with fetal long chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency accumulation of large von Willebrand factor multimers; deficiency of ADAMTS13 may be be complement-mediated or associated with Shiga toxin; may have overlap with TTP
Primary treatment delivery delivery plasmapheresis plasmapheresis
2. Volume depletion
  • Obstetric hemorrhage – Uterine blood flow increases from 50 cc/min prior to pregnancy to approximately 1000 cc/min at term. Thus, pregnancy-related bleeding can be rapid and massive, resulting in acute intravascular volume depletion and AKI. Common causes include:

    Induced or spontaneous abortion – can result in persistent/heavy bleeding, often due to products of conception retained within the uterine cavity

    Ectopic pregnancy – implantation of the pregnancy outside the uterus, usually within the fallopian tubes. Rupture can lead to severe hemorrhage.

    Placenta previa – implantation of the placenta over the internal os of the cervix. This can be associated with heavy bleeding, often painless.

    Placental abruption – separation of the placenta from the uterine wall before delivery of the fetus. This usually presents with abdominal pain, vaginal bleeding, and contractions. Severe or complete abruptions are associated with heavy bleeding, DIC, fetal distress and death.

    Intra- or post-partum hemorrhage – most common reason is uterine atony (failure of the uterus to adequately contract after delivery). Other reasons include retained placenta, genital tract lacerations, coagulopathy, placenta accreta, uterine rupture or inversion.

  • Hyperemesis gravidarum – severe cases of nausea and vomiting of pregnancy. Very severe, refractory, and untreated cases can lead to severe dehydration, hypovolemia and prerenal AKI.

3. Infection – Sepsis can lead to intravascular volume depletion, hypotension, and organ dysfunction including AKI. Common causes of infection leading to sepsis in pregnancy are:

  • Pyelonephritis – This occurs in 1-2% of pregnancies and is associated with maternal and fetal complications including sepsis, preterm labor and adult respiratory distress syndrome. Physiologic changes of pregnancy including ureteral dilation, stasis related to smooth muscle relaxation, and pressure on the bladder and ureters predispose to ascending urinary tract infections. E. coli is the most common organism, followed by other GI organisms such as Klebsiella, Proteus, and enterococcus.

  • Chorioamnionitis – Intrauterine infection involving the chorion and amniotic membranes. This most commonly results from ascending infection of organisms colonizing the lower genital tract. These infections are usually polymicrobial with lower genital tract organisms, peptostreptococcus, Gardnerella, E. coli, Group B streptococcus, and anaerobes.

  • Septic abortion – This has become uncommon in the United States with the legalization of abortion, but it is a significant cause of maternal mortality and morbidity, including AKI, worldwide.

  • Pneumonia

4. Obstruction – Although uncommon in pregnancy, the overdistended, gravid uterus is a risk factor. Additional contributors are:

  • Polyhydramnios (increased amniotic fluid)

  • Multi-fetal gestation (twins and higher)

  • Large uterine fibroids

5. Cardiovascular collapse – While any cardiovascular collapse can lead to AKI during pregnancy, amniotic fluid embolism or “anaphylactoid syndrome of pregnancy” occurs only in pregnancy. It presents suddenly with fulminant respiratory failure, hypoxemia, cardiogenic shock, and hypotension, and is often accompanied by disseminated intravascular coagulation and multi-organ failure. The precise cause is unclear, with early case series describing squamous cells and mucin of fetal origin in the maternal pulmonary vasculature. Maternal mortality is estimated to be as high as 60%.

Other causes of AKI that may be coincident but not specific to pregnancy
  • Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) – As indicated above, there are not pregnancy-specific syndromes but can present like preeclampsia, HELLP syndrome, or acute fatty liver.

  • Autoimmune causes – Primary etiologies such as acute glomerulonephritis, IgA nephropathy or secondary causes such as systemic lupus erythematosus should be considered. Differentiating between acute glomerulonephritis and preeclampsia can be challenging in the late second and third trimester, but is important since the treatments are different. Features that are more suggestive of glomerulonephritides include systemic symptoms (lupus symptoms, preceding infection), active urinary sediment (hematuria, red cell casts), nephrotic-range proteinuria (>2 g), positive ANA, autoantibodies, and abnormal complement levels.

  • Drugs – aminoglycosides, non-steroidal anti-inflammatory medications, to name a few

This is NOT a complete list of all the other etiologies of kidney injury that occur in reproductive-aged women but is intended to highlight some of the more common causes that may coincide with pregnancy.

4. Specific Treatment

Aside from the general principles in the management of PR-AKI discussed in previous sections, specific therapies are directed towards the underlying diagnosis or cause.

  • Hypertensive disorders of pregnancy: Preeclampsia/HELLP syndrome/Acute fatty liver of pregnancy – The only effective cure is delivery of the fetus and placenta. In selected cases of preeclampsia without evidence of end-organ involvement (neurologic symptoms, liver or kidney dysfunction, or low platelets) expectant management may be considered under the care of high-risk obstetricians in a tertiary care facility. Decision regarding mode of delivery (vaginal vs. C-section) is made based on clinical and obstetric factors. In severe cases, supportive care with IV fluids and administration of blood and blood products as indicated is warranted to prevent progression of AKI. Blood pressure must be controlled to prevent maternal cerebrovascular and coronary accidents, with attention to fetal well-being. Intravenous magnesium sulfate (4-gram IV bolus followed by 2 grams/hour) is used to prevent maternal seizures, with close monitoring for any evidence of respiratory depression. Dosage may need to be adjusted and magnesium levels monitored, if there is evidence of renal dysfunction to avoid toxicity. Neonatologists must be involved if delivering a premature fetus.

  • Volume depletion – Obstetric hemorrhage: Correcting the underlying cause to stop ongoing bleeding along with aggressive fluid resuscitation, appropriate replacement with blood and blood products, and correction of coagulation abnormalities are basic management principles of obstetric hemorrhage.

    Ectopic pregnancy – Immediate surgical intervention is warranted to remove the pregnancy and stop bleeding if the patient is hemodynamically unstable. More conservative surgical options and/or medical therapies (such as methotrexate) may be considered if hemodynamically stable.

    Induced or spontaneous abortion – If ongoing and heavy bleeding is due to retained products of conception, then dilation of the cervix and curettage of the uterus (D&C) is generally performed.

    Placenta previa – Delivery by C-section is recommended for heavy, active bleeding. Expectant management may be considered if the bleeding is mild and/or self-limited.

    Placental abruption – Severe abruption with complete separation of the placenta can lead to severe and rapid hemorrhage, coagulopathy, fetal distress and death. Quick recognition is important, followed by stabilization of maternal status, delivery and supportive care. Mild or partial abruptions can be monitored expectantly.

    Intra- or postpartum hemorrhage – Treatment is based on cause. For uterine atony, medical and conservative surgical therapies are used to improve uterine tone; if unsuccessful and bleeding is intractable, then removal of the uterus may be indicated.

  • Infection – Treatment consists of antibiotic therapy along with supportive measures such as intravenous hydration, pressors, and ventilatory support as needed. Broad-spectrum antibiotics should be used initially with attention to local and hospital-based microbiology and organisms. Directed antibiotics can be used once specific culture and sensitivity results are available.

  • Obstruction – Ultrasound is used for initial diagnosis. CT scan and/or pyelogram can be used if necessary. Retrograde ureteral stent placement using cystoscopy or percutaneous nephrostomy can be used to relieve or bypass the obstruction. Delivery may be considered based on gestational age and is often the definitive treatment.

  • Amniotic fluid embolism – Quick recognition with rapid resuscitation, cardiopulmonary support and correction of coagulopathy are the mainstays of treatment.

  • Non-pregnancy-specific etiologies – Treatment is based on the suspected cause. Safety of medication in pregnancy and proper dosing must be considered. Consultation with subspecialists, including maternal-fetal medicine/high-risk obstetricians, is warranted.

5. Disease monitoring, follow-up and disposition

Once the underlying cause is identified and treated, most cases of PR-AKI will stabilize, improve and recover. Generally, the prognosis is good. Short-term renal replacement therapy may be needed in severe cases; long-term dialysis related to PR-AKI is uncommon.

Ongoing follow-up after the acute renal injury is recommended to assess the degree of renal recovery. Furthermore, the cardiovascular and renal changes of pregnancy may take up to 12 weeks to return to baseline. Women with incomplete renal recovery will require close, long-term follow-up to prevent progression. This may include tight control of blood pressure and renoprotective medications. Women with hypertensive disorders of pregnancy are at higher risk of cardiovascular disease over the course of their lifetime and should be monitored on an ongoing basis outside of pregnancy.







Special considerations for nursing and allied health professionals.