ACUTE TUBULAR NECROSIS

ACUTE TUBULAR NECROSIS
by Geoffrey K. Dube and Robert S. Brown
Three days after a complicated right hemicolectomy, a 70
year-old man is noted to have a creatinine of 3.0 mg/dl,
which is increased from his baseline creatinine of 1.0
mg/dl. Vital signs are normal. A thorough physical
examination is notable only for a surgical site which
appears to be healing well. Urine dipstick shows no
protein, heme or leukocyte esterase.
© 2004, Beth Israel Deaconess Medical Center, Inc.
Three days after a complicated right hemicolectomy, a 70 year-old man is
noted to have a creatinine of 3.0 mg/dl, which is increased from his
baseline creatinine of 1.0 mg/dl. Vital signs are normal. A thorough
physical examination is notable only for a surgical site which appears to be
healing well. Urine dipstick shows no protein, heme or leukocyte esterase.
How do the results of the dipstick help narrow your
differential diagnosis?
a. The dipstick is consistent with a nephrotic urine.
b. The dipstick is consistent with a nephritic urine.
c. The dipstick is consistent with a combined nephrotic and
nephritic urine.
d. The dipstick is consistent with a diagnosis of acute
tubular necrosis, pre-renal azotemia, or post-renal
obstruction.
In acute tubular necrosis (ATN), there is
ischemic or toxin-induced damage to the
tubular cells, resulting in cell death and cell
sloughing into the urine. Some tubular cells
may also be shed in the urine due to
defective adhesion to either adjacent cells or
the tubular basement membrane.
In ATN, a large amount of proteinuria, which is
characteristic of the nephrotic syndrome, and a dipstick that
is positive for heme and pyuria, which is characteristic of
the nephritic syndrome, are often absent. However, these
findings may be present if there is a concurrent glomerular
or interstitial process or if there was pre-existing renal
disease. In such cases, the urine dipstick will be positive
for mild-moderate protein, heme, and leukocyte esterase.
In renal failure due to pre-renal azotemia or post-renal
obstruction, the dipstick usually does not show evidence of
proteinuria, hematuria or pyuria unless there is pre-existing
renal disease.
The patient’s urine sediment is shown above. Which of
the following elements are present?
a. Erythrocyte casts
b. Coarse granular, “muddy brown” casts
c. Waxy casts
d. Tubular cell casts
This slide demonstrates several of the coarsely granular,
“muddy brown” casts (single-headed arrows) that are
associated with acute tubular necrosis. It also
demonstrates several waxy casts (double-headed arrow),
many erythrocytes (curved arrow), and cellular debris, all
of which may be seen in ATN.
Our patient’s urine also contained several waxy casts (above left, arrows).
Waxy casts derive their name from their appearance, which looks like melted
wax. Waxy casts are thought to be the end result of granular cast
degeneration. Since cast degeneration is a slow process, waxy casts are
most likely to form in nephrons with diminished urine flow. Waxy casts may
be broad or narrow. Broad casts, as seen in the slide on the right (arrow),
are given their name because they are wider than other types of casts.
Broad casts may have a waxy appearance (as seen in the slide on the right).
They may also have a granular appearance. Broad casts are a sign of
chronic renal failure, since they form in the enlarged tubules of the remaining
hypertrophic nephrons. The slide on the right also contains several
erythrocytes.
Shown above is the urine sediment from another
patient with acute tubular necrosis. It is densely
packed with the coarse granular, “muddy brown”
casts that are characteristic of ATN. There is also a
significant amount of cellular debris.
This slide demonstrates another example of a coarse granular cast. The
granules in these casts may be either coarse or fine and may be either clear
or dark. The granules within the casts are thought to represent degenerating
cells and filtered proteins that have subsequently aggregated. Although
granular casts are a non-specific finding, since they are composed of
elements that are not normally found in urine their presence in the sediment
suggests the presence of intrinsic renal disease. This cast is also an
example of a broad cast. Broad casts develop in hypertrophic nephrons
and are usually seen in chronic renal failure.
Seen above are an example of a finely granular cast (top arrow) and a
coarsely granular cast (middle arrow). All three casts marked by arrows are
bilirubin casts. Bilirubin casts may be seen in the urine of any patient with
elevated levels of conjugated bilirubin. They may be seen in an ATN
sediment if the patient has concurrent acute or chronic liver disease.
Bilirubin may stain casts of any type (e.g., hyaline, granular, waxy, or
cellular). These casts will assume the typical yellow color of bilirubin when
viewed under the microscope.
Tubular cell casts occasionally may be seen in acute tubular
necrosis. Tubular cell casts form when tubular cells complex
with Tamm-Horsfall mucoprotein in the urine. The tubular cells
within the cast appear as round or oval cells with a large
nucleus. If tubular cell degeneration occurs, the distinction
between tubular cell casts and leukocyte casts can be difficult.
In addition to ATN, tubular cell casts may also be seen in any other
condition associated with severe tubular damage, such as acute
interstitial nephritis of any cause, the acute nephritic syndrome, or the
nephrotic syndrome. Lipiduria in the nephrotic syndrome can cause
tubular cell damage, resulting in tubular cell desquamation and the
formation of tubular cell casts. Lipiduria is discussed in more detail in
the section on the nephrotic syndrome.
Our patient’s sediment also contained several isomorphic erythrocytes
(arrow). When ATN is associated with concurrent hematuria, the bleeding is
usually non-glomerular, i.e., acanthocytes and dysmorphic erythrocytes are
absent. The presence of erythrocyte casts in the sediment (as seen in the
slide on the right) should raise suspicion for an acute glomerulonephritis,
vasculitis, or much less commonly, an acute interstitial nephritis. In
glomerulonephritis, erythrocytes should appear dysmorphic and
acanthocytes may be visible. The erythrocytes should be isomorphic in
acute interstitial nephritis. Hematuria is discussed in more detail in the
section on the nephritic syndrome.