Prerenal
First trimester
Hyperemesis gravidarum
Septic abortion
Third trimester
Hemorrhage
Placental abruption
Postpartum
Postpartum hemorrhage
Intrarenal
Third trimester
Preeclampsia
HELLP syndrome
Acute fatty liver of pregnancy
Thrombotic microangiopathy
Postrenal
Any trimester
Obstruction (nephrolithiasis)
Hyperemesis gravidarum
Septic abortion
Hyperemesis Gravidarum
The ARF in hyperemesis is prerenal and results from severe volume depletion. The reduction in renal perfusion is recognized by the rise in blood urea nitrogen, out of proportion to the serum creatinine [1]. Adequate fluid replacement should be instituted to correct the acid-base and electrolyte abnormalities. The hyperemesis should be addressed with a multipronged approach with antiemetics playing an important part in its management.
Septic Abortion
Septic abortion still plays a major role in the development of ARF in developing countries like India. In India, the incidence of ARF due to postabortal complications has dropped from 59.7 % [9] in the 1970s to 20 % [6] at present. This is a direct result of the legalization of abortion and a decrease in the incidence of sepsis.
Causes in the Third Trimester
The causes of ARF in the third trimester can be divided into prerenal and intrarenal (Table 6.1).
Prerenal Causes
Hemorrhage (Placental abruption)
Intrarenal Causes
Preeclampsia
Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome
Acute fatty liver of pregnancy
Thrombotic microangiopathies
The four most common causes of ARF in late pregnancy and the postpartum period are the following:
Preeclampsia
HELLP syndrome
Acute fatty liver of pregnancy
Thrombotic microangiopathy
Preeclampsia
Preeclampsia is the most common form of high blood pressure (BP) that complicates pregnancy. It is the association of new-onset hypertension (≥140/90 mm of Hg) that develops after 20 weeks of gestation, with new-onset proteinuria [11].
When a woman presents with hypertension with no proteinuria, there are other criteria that may lead to classifying her as having preeclampsia [11]. These criteria are the following:
Thrombocytopenia (platelet count less than 100,000/μl)
Impaired liver function (elevated blood levels of liver transaminases to twice the normal concentration)
The new development of renal insufficiency (elevated serum creatinine greater than 1.1 mg/dL or a doubling of serum creatinine in the absence of other renal disease)
Pulmonary edema
New-onset cerebral or visual disturbances
Preeclampsia is classified as non-severe or severe. Signs that point to severe preeclampsia are the following [12]:
Blood pressure ≥160/110 mmHg
Significant proteinuria
Multiorgan involvement
Non-severe preeclampsia is not associated with ARF. Renal failure is unusual even with severe cases (1–5 %) [13]. Severe preeclampsia may be associated with a mild degree of azotemia, due in part to reduced permeability of the glomerular capillary wall [6].
Seventy percent of patients with preeclampsia develop glomeruloendotheliosis which persists in the immediate postpartum period. However, these changes reverse completely in the majority of patients.
The changes in preeclampsia that may lead to acute renal failure in preeclampsia are listed in Table 6.2.
Table 6.2
Causes of ARF in preeclampsia
Primary changes | Glomeruloendotheliosis |
Decrease in GFR | |
Decrease in renal plasma flow | |
Secondary effects | Intravascular volume depletion |
Vasoconstriction | |
Activation of inflammatory cascade | |
Activation of coagulation cascade |
Pregnancy complications superimposed on preeclampsia may precipitate ARF. These complications are the following:
Significant bleeding with hemodynamic instability
Marked disseminated intravascular coagulation (DIC)
Placental abruption which may occur with severe preeclampsia
HELLP Syndrome
HELLP is a syndrome characterized by hemolysis, elevated liver enzymes, and low platelet count. Though it is associated with severe preeclampsia, 15–20 % of women with HELLP syndrome do not have hypertension or proteinuria [15]. Unlike preeclampsia, it is more common in multiparous women.
In the HELLP syndrome, hepatic involvement and hemolysis are more severe than in preeclampsia. Infarction and hemorrhage are more pronounced and rupture of liver hematoma is more common.
ARF occurs in 7–36 % of women with the HELLP syndrome [15, 16]. As in severe preeclampsia, ARF may be a result of direct renal injury or as a consequence of abruption.
The ARF that develops as a consequence of the HELLP syndrome can necessitate dialysis in the acute phase in approximately 10–46 % of pregnant women [17]. However, even women requiring dialysis demonstrate a complete recovery of kidney function [18]. Though the maternal mortality following ARF in the HELLP syndrome is low (1 %), perinatal mortality rate is higher, ranging between 7 and 34 % [15, 19, 20]. Perinatal mortality is more common in early-onset disease, which tends to be more severe [15].
Acute Fatty Liver of Pregnancy
Acute fatty liver of pregnancy (AFLP) is associated with fatty infiltration of hepatocytes without inflammation or necrosis. The disease is caused by an autosomal recessive genetic error. An excessive fetal fatty acid accumulation is released into the maternal circulation. The resulting increased load of long-chain fatty acids is deposited in liver tissue and leads to impaired hepatic function.
Though a rare complication of pregnancy, it is an obstetric emergency which can lead to fulminant hepatic failure. AFLP is associated with acute renal failure in up to 60 % of cases [21–23]. There is decreased renal perfusion or acute tubular necrosis.
In the early stages, it may be difficult to differentiate AFLP from severe preeclampsia and/or HELLP syndrome [24]. The diagnosis should be suspected when preeclampsia is associated with [7]:
Hypoglycemia
Hypofibrinogenemia
Liver function test abnormalities with hyperbilirubinemia
Prolonged partial thromboplastin time (PTT) in the absence of abruptio placentae
Most severely affected women will have complete recovery of liver and kidney function after delivery. However, AFLP is associated with substantial maternal and perinatal morbidity and mortality [25].
Thrombotic Microangiopathies
Thrombotic microangiopathies are a combination of thrombocytopenia and microangiopathic anemia. They are rare and affect 1 in 25,000 pregnancies. They are characterized by the presence of fibrin and/or platelet thrombi in the microcirculation of multiple organs [26]. It might be difficult to differentiate severe preeclampsia from thrombotic microangiopathies because of the similar clinical and histologic characteristics [7]. A history of preceding hypertension and proteinuria favors a diagnosis of preeclampsia.
Thrombotic microangiopathies can be divided into two distinct entities depending on which organ is more affected and the timing of onset:
1.
Thrombotic thrombocytopenic purpura (TTP):
(a)
Neurologic abnormalities are dominant and kidney injury is minimal.
(b)
Diagnosed predominantly in the second and third trimesters.
2.
Hemolytic-uremic syndrome (HUS):
(a)
Renal failure is profound.
(b)
Diagnosed primarily in the postpartum period.
In actual practice the distinction may be difficult since the clinical manifestations of these two conditions may overlap.
TTP is identified by the presence of fever, thrombocytopenia (usually severe), microangiopathic hemolytic anemia, mild renal failure (creatinine <1.4 mg/dL), and neurologic symptoms like disorientation, ataxia, headache, focal changes, seizures, or aphasia [27]. The clinical features of HUS are similar, but neurological involvement is rare while renal involvement is profound.
A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS-13) is also known as von Willebrand factor-cleaving protease (VWFCP). An enzyme produced by liver stellate cells, endothelial cells, and platelets, it is responsible for cleaving large von Willebrand factor multimers. When ADAMTS-13 is deficient (defined by ADAMT-13 activity of <10 %), these large multimers continue to circulate, leading to platelet aggregation and red cell fragmentation. This enzymatic deficiency can be congenital (rare), but is mostly acquired due to autoantibodies [28].
The differentiating features of severe preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome are listed in Table 6.3.
Table 6.3
Severe preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, TTP, and HUS: differentiating features
Severe preeclampsia | HELLP | AFLP | TTP | HUS | |
|---|---|---|---|---|---|
Onset of symptoms | 3rd trimester | 3rd trimester | 3rd trimester | 2nd or 3rd trimester | Postpartum |
Hypertension | 100 % | 80 % | 25–50 % | Occasionally | + |
Acute renal failure | Mild | Mild/moderate | Moderate | Mild/moderate | Severe |
Thrombocytopenia | +/− | + | – | ++ | ++ |
Hemolytic anemia | – | _ | −/+ | ++ | + |
Increased PTT | −/+ | −/+ | + | – | – |
Increased liver transaminase | −/+ | + | ++ | – | – |
ADAMTS-13 activity <10 % | – | – | – | ++ | + |
Renal outcome | Good | Good | Good | Poor | Poor |
Uterine Hemorrhage and ARF
Acute renal failure is especially common in pregnancy complicated by:
Placental abruption
Disseminated intravascular coagulation
Postpartum hemorrhage
Massive hemorrhage is implicated as a cause of ARF in pregnancy. If there is associated severe preeclampsia or HELLP syndrome, the renal consequences of hemorrhage are worsened [29]. Hemorrhage will exacerbate the hypovolemic state already associated with severe preeclampsia and precipitate the development and progression of acute tubular necrosis (ATN).
If acute hemorrhage, and the resultant hypovolemia, is not treated adequately and immediately, transient acute tubular necrosis may result. ATN is potentially reversible and with supportive therapy, the damage can be minimal. Since pregnancy is associated with heightened inflammation and is a prothrombotic state, without immediate intervention, the ATN can progress rapidly to bilateral renal cortical necrosis (BRCN). This almost always leads to permanent and irreversible renal damage. Twenty percent of cases of acute renal failure of obstetric origin progress to BRCN [10].
Diagnosis of ATN:
Urinary sodium >25 mEq/L.
Urine exam shows tubular cell debris and brown granular (pigmented) casts.
Oliguria (50 % of cases).
Diagnosis of BRCN:
Anuria persisting for >1 week
CT with contrast or selective renal angiography (imaging not essential)
Delayed filling
Poor arborization of the interlobar arteries
Absent or nonhomogeneous filling at the level of the cortex
Renal biopsy
Management of ARF in Pregnancy
Treatment of acute kidney injury in pregnancy poses special challenges, as there are risks to both the mother and the fetus. Management is best provided by a multidisciplinary team that involves obstetricians, nephrologists, neonatologists, and other specialists as needed.
The key issues in the management of ARF in pregnancy include:
Correction of hypovolemia when present
Prevention of further injury
Initiation of renal replacement therapy (dialysis) when indicated
Treatment of underlying cause
The delivery of a baby and the placenta as promptly as possible
It would be prudent to discontinue and avoid nephrotoxic drugs as well as to treat any associated infection such as urinary tract infection [30]. Commonly used nephrotoxic drugs include nonsteroidal anti-inflammatory drugs (NSAIDs) and aminoglycoside antibiotics such as amikacin and gentamicin. Patients who are hypovolemic would require intravenous fluids to restore and maintain renal as well as uroplacental perfusion. Although rarely undertaken in pregnancy, it would also be important to avoid radiocontrast studies in patients with ARF.
Complications of ARF in Pregnancy
Complications of ARF in pregnancy are similar to other patient groups and include:
Hypertension
Electrolyte abnormalities
Hyperkalemia
Hypocalcemia
Metabolic acidosis
Anemia
Volume overload
Hypertension
Hypertension is common in patients with ARF, and there is no consensus about the blood pressure level at which antihypertensives should be started in pregnancy [12, 31, 32]. NICE guidelines [33] recommend starting treatment when the blood pressure is ≥150/100 mm of Hg. Labetalol is the initial drug of choice. The target blood pressure to be achieved is a systolic of <150 mm of Hg and a diastolic blood pressure between 80 and 100 mm of Hg.
Other antihypertensives such as methyldopa, hydralazine, and nifedipine can also be used safely in pregnancy. Hydralazine is often used intravenously in pregnant women who present with severe hypertension due to preeclampsia [34]. However, a meta-analysis of randomized controlled trials for the treatment of moderate to severe hypertension in pregnancy was not in favor of using hydralazine as its use was associated with a higher incidence of maternal side effects including hypotension, placental abruption, and oliguria [35]. Methyldopa should also be switched to an alternative antihypertensive in the postnatal period as it increases the risk of postnatal depression [36]. Other commonly used antihypertensives such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) should be avoided in pregnancy.
Hyperkalemia
Hyperkalemia can be treated with either insulin and dextrose or cation exchange resin although persistent and severe hyperkalemia would be an indication for renal replacement therapy [37]. Care should be taken to avoid hypoglycemia when treating hyperkalemia with insulin and dextrose, given the risks to the mother as well as the fetus.
Metabolic Acidosis
Mild acidosis is common in pregnancy and sodium bicarbonate can be used to correct worsening metabolic acidosis [38].
Anemia
Anemia is also common in ARF and can be managed with blood transfusion which, however, may exacerbate hyperkalemia and volume overload in patients with renal failure [39]. Human recombinant erythropoietin (EPO) has been used safely in pregnancy, but higher doses may be required to achieve the desired target hemoglobin [40].
Renal Replacement Therapy (RRT) or Dialysis
The indications for renal replacement therapy (RRT) or dialysis are similar to other patients with ARF and are listed in Table 6.4.
Table 6.4
Indications for renal replacement therapy
1. Electrolyte imbalance |
2. Metabolic acidosis |
3. Volume overload |
4. Symptomatic uremia (pericarditis, neuropathy, mental status changes) |
No specific guidelines exist to steer RRT in pregnant women. However, relying on experience with RRT in nonpregnant women alone fails to take account the impact of the physiological changes that often accompany pregnancy [41]. Glomerular filtration rate increases by about 50 % in pregnancy as a result of increased renal plasma flow [42]. These changes occur early and persist till term, resulting in a fall in serum creatinine by about 20–30 % during pregnancy, compared to pre-pregnancy values [43]. Given this, standard dose of RRT used in nonpregnant patients may not be adequate in the setting of ARF in pregnancy.
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