TITLE
ACUTE KIDNEY INJURY IN THE PREGNANT PATIENT
Rosemary Nwoko, Darko Plecas and Vesna D. Garovic
1
ABSTRACT
Acute kidney injury (AKI) is costly and associated with increased mortality and
morbidity. An understanding of the renal physiologic changes that occur during
pregnancy is essential for proper evaluation, diagnosis, and management of AKI.
As in the general population, AKI can occur from pre-renal, intrinsic, and postrenal causes. Major causes of pre-renal azotemia include hyperemesis
gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic
etiologies include infections from acute pyelonephritis and septic abortion,
bilateral cortical necrosis, and acute tubular necrosis. Particular attention should
be paid to specific conditions that lead to AKI during the second and third
trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of
pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is
the recommended therapeutic option, with additional therapies indicated for each
specific disease entity. An understanding of the various etiologies of AKI in the
pregnant patient is key to the appropriate clinical management, prevention of
adverse maternal outcomes, and safe delivery of the fetus. In pregnant women
with pre-existing kidney disease, the degree of renal dysfunction is the major
determining factor of pregnancy outcomes, which may further be complicated by
a prior history of hypertension.
2
KEY WORDS
Acute kidney injury (AKI) - TTP-HUS (thrombotic thrombocytopenic purpuraHemolytic uremic syndrome) - HELLP (hemolysis, elevated liver enzymes, low
platelets) - TMA (thrombotic microangiopathy) - aHUS (atypical hemolytic uremic
syndrome).
INTRODUCTION
Acute kidney injury (AKI) can be defined as the sudden loss of renal
function associated with a rise in creatinine levels above a known baseline.
In this setting, clearance of nitrogenous wastes, as well as extracellular
volume and electrolyte regulation are impaired. AKI in the general
population is associated with increased mortality, increased length of
hospital stay and financial costs [1].
In the pregnant population the
incidence of all AKI cases, including dialysis dependence, is less than 1%
in the Western world, with reduced frequency and improved mortality [2]
since the 1960s. It is important to note that epidemiologic data on the
incidence and prevalence of AKI in pregnancy may vary due to different
diagnostic criteria and variable cut-off values for serum creatinine levels
that define kidney injury, the lack of creatinine data in this young, healthy
population, and the variability in ethnicity and socioeconomic class. New
cases of pregnancy-related AKI have declined from approximately 1/3000 to
3
1/15,000 – 20,000 since the 1960s [3]. Two main factors may be responsible
for the overall decline in the incidence of pregnancy-related AKI:
improvement in pre-natal care and a decrease in the rate of illegal, septic
abortions in developed countries. It is possible that the use of
antiprogesterone drugs, such as mifepristone, might have contributed to
the declining septic abortion rates, although there is a paucity of data
regarding this association.
During pregnancy, AKI can be due to any of the same disorders that affect
the general population, such as pre-renal, intrinsic and post-renal causes.
In the text that follows, we will review AKI in pregnancy in the context of
pre-renal, intrinsic and post-renal etiologies, and will address its
presentation and onset with respect to gestational age (i.e., trimester of
pregnancy), as this may help to facilitate making a differential diagnosis.
Finally, AKI may occur as a new condition, a pre-existing, albeit
unrecognized condition, or as a pre-existing condition in patients with
normal or impaired renal function. Among conditions that may lead to AKI,
and which commonly occur during the second and/or third trimester,
special attention will be given to those disease processes that are unique
to the pregnancy state.
PHYSIOLOGIC CHANGES IN PREGNANCY
Most organ systems in a pregnant female undergo changes in order to
accommodate the growing fetoplacental unit.
There are considerable
changes that occur in the urinary tract system: both kidneys and ureters
4
increase in size by 1 to 1.5 cm [4], accompanied by dilation of the renal
pelvis and calyx. This dilation of the urinary system is due to the hormonal
effects of progesterone, external compression by the gravid uterus and
morphologic changes in the ureteral wall [5]. Progesterone also reduces
ureteral peristalsis, contraction and tone. Decreased bladder tone, bladder
hyperemia and edema potentiate asymptomatic bacteruria, while bladder
flaccidity may affect the vesicoureteral valve, leading to vesicoureteral
reflux [5]. The result of these physiological changes are increased risks for
urinary stasis, urinary tract infection, and, ultimately, pyelonephritis. The
systemic vasodilatory state, typical of pregnancy, increases renal
perfusion and glomerular filtration rate (GFR).
Due to the rise in GFR,
hypouricemia and increased urine protein excretion occur. Systemic
vasodilation leads to the stimulation of anti-diuretic hormone (ADH) release
and increased thirst, resulting in a decrease in plasma osmolality and
plasma sodium concentration by 4 to 5 mEq/L [6]. Minute ventilation
increases
due
to progesterone-induced
stimulation
of
the
central
respiratory center in the brain. This results in a decrease in pCO2 and a
mild chronic respiratory alkalosis, which is compensated for by renal
excretion of bicarbonate.
PRE-RENAL AZOTEMIA
This is defined as a decrease in the effective intravascular volume leading to
decreased renal perfusion. Causative factors seen in the non-pregnant
5
population, such as vomiting, diarrhea, congestive heart failure, nephrotic
syndrome and diuretic use, are possible etiologies in the pregnant patient [2].
Pre-renal azotemia during pregnancy may be due to hypovolemia resulting from
hyperemesis gravidarum, diuresis, and hemorrhage from trauma, placental
previa, placental abruption, a ruptured or atonic uterus or intra-operative
bleeding. It may also result from decreased cardiac output in the setting of preexisting valvular heart disease, ischemia or cardiomyopathy from any cause.
Finally, decreased renal perfusion may also occur in the settings of anaphylaxis,
sepsis,
and
the
use
of
non-steroidal
anti-inflammatory
drugs/
cyclooxygenase-2 inhibitors (NSAIDs/COX-2 inhibitors).
The most common causes of prerenal azotemia in pregnancy include
hyperemesis gravidarum and hemorrhage. Hyperemesis gravidarum is defined
as severe and persistent nausea and vomiting leading to weight loss, exceeding
5 percent of the pre-pregnancy body weight, and ketonuria [7]. These patients
present in the first trimester of pregnancy with acute renal failure
associated
with
a
hypokalemic,
metabolic
alkalosis.
Conceivably,
metabolic alkalosis may be compensated by a respiratory response, i.e,
hypoventilation,
but
clinical
studies
supporting
this
compensatory
response are limited. As this occurs in the setting of preexisting
respiratory alkalosis, which is a known physiological consequence of the
direct progesterone effect on the respiratory center in pregnant women,
further evaluation with a blood gas may be necessary in order to evaluate
the respiratory and metabolic components and diagnose the underlying
acid-base disorder. Other laboratory abnormalities can include an increase in
hematocrit (hemoconcentration), mild elevations in aminotransferases [8], as well
6
as mild hyperthyroidism. The hyperthyroidism is thought to be due to the thyroid
stimulating activity of human chorionic gonadotropin [9]. Treatment with
antiemetics and intravenous fluids usually corrects the acid-base, electrolyte and
renal abnormalities [2].
The differential diagnoses of hemorrhage during the first trimester of pregnancy
differ from the second or third trimesters. Specifically, in the third trimester,
placenta previa, abruptio placenta (preeclampsia and prior hypertension are risk
factors), uterine rupture and vasa previa may occur.
INTRINSIC KIDNEY INJURY
Damage to the tubulo-interstitium, glomerulus, or cortex can lead to intrinsic
kidney damage during pregnancy. Causes of intrinsic AKI include tubular and
interstitial damage from acute tubular necrosis (ATN), contrast-induced
nephropathy, infections, nephrotoxic drugs and myoglobinuria. The usual causes
of glomerulonephritis (GN) in the non-pregnant patient, such as lupus nephritis,
post-infectious GN, and focal segmental glomerulosclerosis (FSGS) may occur.
The renovascular system can be affected in conditions such as HUS/TTP, antiphospholipid syndrome, scleroderma renal crisis, HELLP and pre-eclampsia/
eclampsia.
INFECTION
Urinary tract infections are very common in pregnancy, but rarely cause AKI,
except when accompanied by septicemia or hypotension.
However, acute
pyelonephritis, without signs of sepsis or hypotension, may result in abscess
7
formation and kidney injury [10], although it is unclear why these patients develop
significant renal dysfunction.
A more common infectious cause of renal failure associated with pregnancy is
septic abortion, which has a higher incidence in underdeveloped countries.
These patients present with signs and symptoms of septic shock and/or
disseminated intravascular coagulation (DIC). Renal failure may be due to
volume contraction, acute tubular necrosis or bilateral renal cortical necrosis.
Treatment includes supportive care with intravenous fluids and appropriate
antibiotics. Dilatation and curettage, as well as hysterectomy may be needed in
certain cases.
Thrombotic Microangiopathy (TMA)
Thrombotic microangiopathy is a pathologic diagnosis that may occur with
pregnancy, in the setting of severe preeclampsia, with HELLP (hemolysis,
elevated liver enzymes and low platelets) syndrome, TTP (thrombotic
thrombocytopenic purpura), HUS (hemolytic uremic syndrome), as well as
atypical variants of HUS. Although the term TTP-HUS will be used frequently
in the following text, it is important to note that both can and do occur as
separate disease processes (Table 1). The main feature of platelet thrombi
and/or fibrin in the microvasculature, can lead to multi-organ dysfunction. The
above differentials should be considered in patients who present in late
pregnancy with acute renal failure, microangiopathic hemolytic anemia and
thrombocytopenia.
8
Preeclampsia is characterized by hypertension and proteinuria occurring after 20
weeks gestation. Renal failure is unusual in this setting. Pregnancy termination is
the recommended and effective therapy, with abnormalities resolving postpartum, although microalbuminuria may persist for weeks post delivery.
It is widely accepted that preeclampsia occurs in the setting of placental hypoxia
and underperfusion. In contrast to normotensive pregnancies, placental spiral
arteries in preeclampsia fail to lose their musculoelastic layers, ultimately leading
to decreased placental perfusion [11] [12]. Placental hypoxia ensues, which is
viewed frequently as an early event that may cause placental production of
soluble factors leading to endothelial dysfunction. Recent studies have provided
evidence that preeclampsia is associated with elevated levels of the soluble
receptor for vascular endothelial growth factor (VEGF) of placental origin. This
soluble receptor, commonly referred to as sFlt-1 (from fms-like tyrosine kinase
receptor-1), may bind and neutralize VEGF, and thus decrease free VEGF levels
that are required for active fetal and placental angiogenesis in pregnancy.
Therefore, elevated sFlt-1 may be the missing link between placental ischemia
on one side and endothelial dysfunction, mediated by sFlt-1 neutralization of
vascular growth factors, on the other.
HELLP syndrome is associated with severe hypertension/preeclampsia during
pregnancy. Its overall incidence is 1 to 2 per 1000 pregnancies, and occurs in 1020 percent of severe preeclamptics/eclamptics. The underlying mechanism of
injury is not fully understood, as 15 to 20 percent of affected patients do not have
hypertension or proteinuria.
In addition to sFlt-1, elevated levels of soluble
endoglin may contribute to maternal endothelial dysfunction in HELLP patients
9
[13] [14]. Recent studies are elucidating the role of the dysfunctional
complement alternative pathway (CAP) as a risk factor for HELLP. Mutations
can occur in the major regulatory proteins of the CAP, factor H, membrane
cofactor protein and factor I. In a case series of 11 patients diagnosed with
HELLP, 4 patients were found to have missense mutations in 1 of 3 genes
encoding for CAP regulatory proteins, which were not found in 100 healthy
controls from the same ethnic background [15]. Low C3 and factor B levels may
also predispose to HELLP syndrome, even when no specific mutations are found
in these genes [15].
The clinical manifestations of HELLP syndrome include [16]), abdominal pain
(midepigastric, right upper quadrant or below the sternum) nausea, vomiting and
malaise. Hypertension (blood pressure > 140/90) and proteinuria may be either
present or absent in these patients [17]. Renal failure also may be present, and
the frequency of CAP abnormalities may be higher in these patients compared to
patients who present without renal involvement [15]. The presence of
microangiopathic hemolytic anemia with schistocytes on blood smear, low
platelets and elevated liver enzymes are the diagnostic criteria for HELLP. Other
indicators of hemolysis include an elevated lactate dehydrogenase (LDH) or
indirect bilirubin, and low haptoglobin. However, there is no consensus as to the
degree of laboratory abnormalities that are diagnostic of HELLP syndrome.
Imaging, such as computed tomography (CT) or magnetic resonance imaging
(MRI), may be helpful in cases where complications such as hepatic hematoma,
infarction or rupture occur [18].
10
HELLP may be difficult to differentiate from TTP-HUS, as thrombocytopenia and
microangiopathic hemolysis occur with both conditions. However, the presence
of elevated liver enzymes strongly suggests HELLP syndrome (Table 1).
TTP-HUS is a form of TMA that can be due to a deficiency in ADAMTS13 (TTP),
a von Willebrand factor (vWF) processing enzyme, or due to mutations in genes
that encode proteins responsible for regulating the CAP system (atypical HUS).
Deficiency in ADAMTS13 can be acquired or genetic, and patients have severe
thrombocytopenia and mild renal involvement. These patients commonly develop
neurological manifestations, and typically present in the second or third
trimesters of their pregnancies, when ADAMTS13 levels tend to fall [19]. Atypical
HUS (non-Shiga toxin) is associated with mutations in genes coding for proteins
in the alternative complement pathway. This results in spontaneous and
excessive activation of CAP leading to endothelial cell damage. Complement
abnormalities occur due to acquired anti-Factor H antibodies, inactivating
mutations in factors H and I, or membrane co-factor protein, and activating
mutations in factor B or C3 coding genes. Patients predominantly have renal
involvement, and thrombocytopenia may not be as severe as seen in TTP-HUS.
The pregnancy state may trigger abnormal complement activation leading to
atypical HUS. In a recent series of 100 patients with atypical HUS, 21 percent
developed during pregnancy, with 79% occurring post-partum [20]. Complement
abnormalities were detected in 18 of the 21 patients, and this patient group had
poor outcomes with respect to time to end stage renal disease (ESRD), as well
as risks of fetal loss and preeclampsia [20]. The interactions among complement
components, angiogenic factors, and the clinical features of preeclampsia were
11
documented further using pregnant mouse models. Results of this study
demonstrated that complement activation targets the placenta, leading to
endothelial dysfunction [21] through the release of anti-angiogenic factors that
have been associated previously with hypertension and proteinuria [22]
Renal biopsy is rarely needed for the diagnosis of these conditions, as clinical
and laboratory data are usually sufficient to distinguish and establish a diagnosis.
In addition, renal biopsy findings may be characteristic of TMA, but may not
differentiate among disease entities (e.g. HELLP versus atypical HUS). Light
microscopy typically shows double-contouring of the glomerular basement
membrane and mesangiolysis, with vascular changes such as arteriolar and
capillary thrombi
TTP-HUS may occur de novo with pregnancy, may relapse during pregnancy
and/or recur with subsequent pregnancies. The distinction among severe forms
of preeclampsia (and HELLP in particular), TTP, and HUS may be facilitated by
certain clinical and laboratory features, but it is not always possible (Table 1).
Renal biopsy should be considered if the laboratory evaluation is nondiagnostic and/or in the presence of co-morbidities, such as systemic
lupus erythematosus, where the renal biopsy findings may have a major
impact on a patient’s treatment. For example, biopsy-proven lupus
nephritis optimally is managed with immunosuppression, whereas delivery,
even remote from term, is indicated for HELLP syndrome. In pregnant
patients with adequate blood pressure control and normal coagulation
parameters, renal biopsy can be safely performed [23]. However, renal
biopsy is typically not advisable after 32 weeks of gestation.
12
Finally, a thrombotic microangiopathy, similar to TTP, can occur in patients with
anti-phospholipid antibodies presenting with renal disease, thrombocytopenia,
and hemolytic anemia during pregnancy [24]. In these patients, it is possible that
a hypercoagulable state, which is characteristic of pregnancy, may contribute to
the pre-existing subclinical thrombotic state due to the presence of antiphospholipid antibodies, resulting in a clinically apparent syndrome of thrombotic
microangiopathy during pregnancy (Figure 2). The role of anticoagulation in the
prevention/treatment of renal involvement in these patients is unclear.
ACUTE FATTY LIVER OF PREGNANCY
Fatty infiltration of hepatocytes may occur during pregnancy, and can be
associated with renal failure in 60% of cases [25]. It should be suspected in
women with preeclampsia. This is a disease of the third trimester of pregnancy,
and patients present with elevated liver function tests, thrombocytopenia,
hypofibrinogenemia, hypoglycemia and coagulation abnormalities [26]. In severe
cases, patients may present with encephalopathy. Renal failure may be due to
acute tubular necrosis and decreased renal perfusion.
The diagnosis is made clinically based upon presentation, laboratory and
imaging data. A liver biopsy is not necessary, but may be useful in atypical
presentations [26]. Characteristic liver biopsy findings consist of microvesicular
13
fatty infiltration of hepatocytes in the central and mid-zonal lobular regions, with
sparing of the portal tracts [27].
Primary treatment includes maternal stabilization, with correction of coagulation
abnormalities (with fresh frozen plasma, platelets, cryoprecipitate and red blood
cells) as needed and prompt delivery. Acute fatty liver of pregnancy may recur in
subsequent pregnancies, although the risk of recurrence is unknown.
RENAL CORTICAL NECROSIS
Renal cortical necrosis is a rare, but catastrophic process secondary to
ischemic necrosis of the renal cortex [4].It occurs as the end result of
various severe pregnancy complications, including abruptio placentae,
placenta previa, prolonged intrauterine fetal death or amniotic fluid
embolism [28]. Obstetric etiologies account for approximately 50-70% of
cases of renal cortical necrosis [5]. Patients present with the abrupt onset
of oliguria or anuria, gross hematuria, flank pain and hypotension [29]. The
diagnosis can be made by ultrasonography or CT scan. There is no specific
treatment available and many patients will require dialysis, with 20-40 % of
patients having partial renal recovery [29]. In one series, 42 of 45 patients
(87.5%) with biopsy-confirmed renal cortical necrosis were dialysis
dependent upon hospital discharge [30]. In patients who recover partial
renal function, creatinine clearance stabilizes between 15 and 50 ml/min
[29].
POST-RENAL KIDNEY INJURY
14
A common finding during the later stages of pregnancy is mild to moderate
dilatation of the collecting system from the gravid uterus, and relaxation of the
ureteral smooth muscle [31]. While the majority of patients are asymptomatic
and have normal renal function [31], this functional hydronephrosis, in rare
cases, may cause renal failure. Placing the patient in a lateral recumbent
position, thereby relieving uterine pressure on the ureter, may improve
urine output and creatinine. In contrast, patients with obstruction due to
either extrinsic (e.g. uterine fibroid), or intrinsic (e.g. renal stone) causes,
are commonly symptomatic and present with varying degrees of renal
insufficiency. Post-renal kidney injury occurs from obstruction of part or all of
the genitourinary system. Kidney stones, papillary necrosis, surgical ligation,
cervical cancer, and urethral obstruction by catheter malfunction, or blood clots
may be inciting factors. In the above cases, treatment involves relief of the
obstruction.
PREEXISTING RENAL DISEASE
Approximately 4% of childbearing-age women have chronic kidney disease, with
diabetic nephropathy being the most common cause found in pregnant women
[32]. A variety of primary and/or systemic kidney diseases can occur in the
pregnant population and lead to an increased incidence of fetal prematurity, low
birth weight and fetal loss [32]. Due to major obstetric and neonatologic
advancements, fetal outcomes in women with impaired renal function have
improved in recent years [33]. However, the risk for fetal loss remained higher in
pregnant patients with preexisting renal insufficiency compared to a control group
of women with medical problems other than renal disease [34] Factors predicting
15
fetal loss included severity of proteinuria and degree of renal dysfunction [34].
Other risk factors for complications include decreased GFR, nephrotic range
proteinuria, advanced maternal age and the presence of underlying diseases,
such as diabetes mellitus, hypertension, and active systemic lupus nephritis.
Pregnancy likely does not contribute to the progression of renal insufficiency
when the maternal creatinine is less than 1.4 mg/dl and the blood pressure is
normal. There are increased risks of renal decline and pregnancy loss with a
creatinine ≥1.4 mg/dl,; women with creatinine values of 3 mg/dl or greater should
be strongly discouraged against pregnancy, due to the high risks for adverse
fetal outcomes and maternal events, including further renal decline [35]. Other
data have shown an increased risk of deterioration of maternal renal function
when the creatinine clearance at conception is less than 25-30 ml/min [33, 36].
Some experts have suggested that patients with anti-phospholipid antibody
syndrome and a history of arterial thrombotic events (strokes, in particular),
should be advised against becoming pregnant [37]. These women, despite
adequate anticoagulation, appear to be at risk for recurrent strokes. Poorly
controlled diabetes mellitus and active lupus nephritis [38] are also relative
contraindications to pregnancy. Patients with preexisting renal disease
should undergo preconception counseling prior to attempting to conceive.
Diabetic patients should be closely monitored by an endocrinologist, with
goals for tight diabetic control before conception.
A minimum of 6
consecutive months without a flare, as well as stable renal function with a
creatinine <1.4 mg/dL, is required prior to conception in lupus patients [39]
In
patients
with
lupus
nephritis,
16
in
remission,
teratogenic
anti-
hypertensives and immunosuppressives must be changed to safe
alternatives prior to conception.
MANAGEMENT
An understanding of the physiologic changes occurring during pregnancy, as well
as early identification of women with pre-existing renal dysfunction, will enable
proper management of AKI that may occur during pregnancy. Therapy should be
directed at the underlying cause, and delivery of the fetus may be required in
certain instances, as discussed above. Severe renal failure may require dialysis,
and both hemodialysis and peritoneal dialysis can be safely used [40] [41].
Similar to non-pregnant patients, plasma exchange should be considered for
those with peri-partum TTP-HUS. For patients with ESRD undergoing dialysis, it
is crucial to prevent intrauterine azotemia, manage anemia, provide adequate
nutritional support and avoid dialysis-associated hypotension.
Volume contraction from dehydration and hemorrhage from any cause can be
readily managed by resuscitation with intravenous fluids and blood products.
Urinary tract infections should be treated with appropriate antibiotic therapy that
is safe for both mother and fetus. Antibiotics should always be adjusted for the
level of GFR. Renal obstruction can be treated conservatively or with surgical
interventions.
CONCLUSION
In this review, we have discussed the different etiologies of AKI, in general, and
those unique to pregnancy. The management of AKI during pregnancy presents
a challenge that requires knowledge of potential causative factors, proper
17
evaluation and treatment, and consideration of both maternal and fetal wellbeing. With respect to pregnancy-specific disorders, such as preeclampsia and
HELLP, their etiologies and pathogeneses remain elusive, resulting in a failure to
develop specific preventive and treatment options. Future research may be
crucial in identifying the underlying pathogenetic mechanisms and related
therapeutic targets.
18
TABLE 1
Preeclampsia
HUS
TTP
Time of onset
Late 3rd trimester
Post-partum
2nd and 3rd trimesters
Renal failure
Unusual
Common
Minimal or absent
Renal prognosis
Recovery
76% ESRD[20]
Fair
Neurological
Present
Minimal or absent
Dominant
Low platelet count
Present (HELLP)
Present
Present
DIC
Present
Absent
Absent
Absent
Absent
Present (HELLP)
Present
Absent
Mild to moderate
Absent
Severe
findings
Abnormal
liver Present (HELLP)
enzymes
Complement
alternative
pathway
Low ADAMTS13
19
FIGURE LEGENDS
Table1. Differential diagnosis of TMA in pregnancy: the role of clinical and
laboratory findings
Figure 1. Flow diagram showing the differential diagnosis of thrombotic
microangiopathy.
Figure 2 Light (A) and electron microscopy (B) from a renal biopsy consistent
with TMA. A 43-year old admitted at 33 weeks gestation for increasing edema
and decreased urinary output. This was the patient’s first pregnancy (twins)
through in vitro fertilization. She presented in hemorrhagic shock, with elevated
liver enzymes, and LDH, thrombocytopenia and a creatinine of 2.7 mg/dl. A
diagnosis of HELLP was made and the patient underwent urgent Cesarean
section. Her kidney function further deteriorated post-partum and she required
hemodialysis. As her clinical course was not consistent with HELLP syndrome
(Table 1), additional work up was initiated. ADAMTS 13 levels ranged within 4568% of normal, with normal C3, C4, CH50, factor H and factor I levels. Factor H
antibody was negative. Lupus anticoagulant was positive. Her renal biopsy was
consistent with TMA.
2A: Light microscopy showing fibrin (yellow thin arrow) and a thrombus (green
thick arrow) within a vessel that propagates to the vascular pole of the
20
glomerulus. There is also evidence of endothelial cell swelling (dashed black
arrow) resulting from inflammation and injury.
2B: Electron microscopy showing foot process effacement (multiple short arrows)
and the formation of new glomerular basement membrane (thin long arrow), the
process of double-contouring. She has remained on chronic hemodialysis and is
currently being evaluated for a renal transplant.
21
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