CAST

Casts are the only elements found in the urinary sediment that are unique to the kidney.
They are formed within the lumens of the distal convoluted tubules and collecting ducts,
providing a microscopic view of conditions within the nephron. Their shape is
representative of the tubular lumen, with parallel sides and somewhat rounded ends,
and they may contain additional elements present in the filtrate.

✓ Examination of the sediment for the detection of casts is performed using lower
power magnification. When the glass cover-slip method is used, low-power
scanning should be performed along the edges of the cover slip.

✓ Observation under subdued light is essential, because the cast matrix has a low
refractive index. Similar to many other sediment constituents, the cast matrix
dissolves quickly in dilute, alkaline urine.

✓ Once detected, casts must be further identified as to composition using high-

power magnification. They are reported as the average number per 10 LPFs.

Cast Composition and Formation

✓ The major constituent of casts is uromodulin ( also known as Tamm’s Horsfall

Protein)

✓ Other proteins present in the urinary filtrate, such as albumin and

immunoglobulins, are also incorporated into the cast matrix.

✓ Under normal conditions, uromodulin is excreted at a relatively constant rate. The

rate of excretion appears to increase under conditions of stress and exercise,
which may account for the transient appearance of hyaline casts when these
conditions are present.

✓ The protein gels more readily under conditions of:

1. Urine-flow stasis

 2. Acidity

3. Presence of sodium and calcium.

✓ Uromodulin protein is found in both normal and abnormal urine and, as

discussed previously, is a major constituent of mucus. It is not detected by
reagent strip protein methods. Therefore, the increased urinary protein frequently
associated with the presence of casts is caused by underlying renal conditions.

✓ Scanning electron microscope studies have provided a step-by-step analysis of

the formation of the uromodulin protein matrix:

1. Aggregation of uromodulin protein into individual protein fibrils attached to the

RTE cells

2. Interweaving of protein fibrils to form a loose fibrillar network (urinary

constituents may become enmeshed in the network at this time)

3. Further protein fibril interweaving to form a solid structure

4. Possible attachment of urinary constituents to the solid matrix

5. Detachment of protein fibrils from the epithelial cells

6. Excretion of the cast

✓ As the cast forms, urinary flow within the tubule decreases as the lumen
becomes blocked. The accompanying dehydration of the protein fibrils and
internal tension may account for the wrinkled and convoluted appearance of
older hyaline casts.

✓ The width of the cast depends on the size of the tubule in which it is formed.
Broad casts may result from tubular distension or, in the case of extreme urine
stasis, from formation in the collecting ducts.

✓ Formation of casts at the junction of the ascending loop of Henle and the distal
convoluted tubule may produce structures with a tapered end. These have been

 referred to as cylindroids, but they have the same significance as casts. In fact,
the presence of urinary casts is termed cylindruria.

✓ The appearance of a cast is also influenced by the materials present in the filtrate
at the time of its formation and the length of time it remains in the tubule. Any
elements present in the tubular filtrate, including cells, bacteria, granules,
pigments, and crystals, may become embedded in or attached to the cast matrix.

Hyaline Casts

The most frequently seen cast is the hyaline type, which consists almost entirely of
uromodulin.

Appearance ✓ Appear colorless in unstained sediments and have a

refractive index similar to that of urine
✓ Sternheimer-Malbin stain produces a pink color in hyaline
casts
✓ The morphology of hyaline casts is varied, consisting of
normal parallel sides and rounded ends, cylindroid forms,
and wrinkled or convoluted shapes that indicate aging of
the cast matrix
Indications ✓ Increased numbers following strenuous exercise,
dehydration, heat exposure, and emotional stress.
✓ Pathologically: Increased in acute glomerulonephritis,
pyelonephritis, chronic renal disease, and congestive heart
failure

 RBC Casts

Whereas the finding of RBCs in the urine indicates bleeding from an area within the
genitourinary tract, the presence of RBC casts is much more specific, showing bleeding
within the nephron. Examination under high-power magnification should concentrate on
determining that a cast matrix is present, thereby differentiating the structure from a
clump of RBCs. Because of the serious diagnostic implications of RBC casts, the actual
presence of RBCs must also be verified to prevent the inaccurate reporting of non-
existent RBC casts. It is highly improbable that RBC casts will be present in the
absence of free-standing RBCs and a positive reagent strip test for blood (Fig. 6–50).

 Appearance ✓ Easily detected under low power by their orange-red color.

They are more fragile than other casts and may exist as
fragments or have a more irregular shape as the result of
tightly packed cells adhering to the protein matrix (Figs. 6–
48 and 6–49).
✓ As an RBC cast ages: cell lysis begins and the cast
develops a more homogenous appearance, but retains the
characteristic orange-red color from the released
haemoglobin (Fig. 6–51).
▪ These casts may be distinguished as blood casts,
indicating greater stasis of urine flow.
✓ Homogenous orange-red or red-brown casts may be
observed in the presence of massive hemoglobinuria or
myoglobinuria.
✓ Granular, dirty, brown casts representing hemoglobin
degradation products such as methemoglobin may also be
present (Fig. 6–52).
▪ They are associated with the acute tubular necrosis
often caused by the toxic effects of massive
hemoglobinuria that can lead to renal failure.
▪ Present in conjunction with other pathologic findings
such as RTE cells and a positive reagent strip test
for blood.
Objective and ✓ Both types of casts are reported as the number of RBC
Reporting casts per LPFs.

 Indications ✓ RBC casts are primarily associated with damage to the

glomerulus (glomerulonephritis) that allows passage of the
cells through the glomerular membrane; however, any
damage to the nephron capillary structure can cause their
formation.
✓ RBC casts associated with glomerular damage are usually
associated with proteinuria and dysmorphic erythrocytes.
✓ RBC casts have also been observed in healthy individuals
following participation in strenuous contact sports.

 WBC Casts

Appearance ✓ WBC casts are composed of neutrophils; therefore, they

may appear granular, and, unless disintegration has
occurred, multilobed nuclei will be present (Fig. 6–53).
✓ Supravital staining:
▪ Demonstrate the characteristic nuclei (Fig. 6–54). It
is particularly helpful for differentiating WBC casts
from RTE casts. Observation of free WBCs in the
sediment is also essential (Fig. 6–55).
✓ Hansel and Wright’s stains:
▪ Eosinophil casts may be present in appropriately
stained specimens.
Objective and Visible under low-power magnification but must be positively
Reporting identified using high power
Indications ✓ Signifies infection or inflammation within the nephron.
✓ Most frequently associated with pyelonephritis and are a
primary marker for distinguishing pyelonephritis (upper
UTI) from cystitis (lower UTI).
✓ Also present in non-bacterial inflammations such as acute
interstitial nephritis and may accompany RBC casts in
glomerulonephritis.
✓ Bacteria are present in cases of pyelonephritis, but are not
present with acute interstitial nephritis.

 Bacterial Casts

Bacterial casts containing bacilli both within and bound to the protein matrix are seen in
pyelonephritis. They may be pure bacterial casts or mixed with WBCs. Identification of
bacterial casts can be difficult, because packed casts packed with bacteria can
resemble granular casts. Their presence should be considered when WBC casts and
many free WBCs and bacteria are seen in the sediment. Confirmation of bacterial casts
is best made by performing a Gram stain on the dried or cytocentrifuged sediment.

Epithelial Cell Casts

Appearance ✓ Staining and the use of phase microscopy can be helpful to

enhance the nuclear detail needed for identification (Figs. 6–58 A
and B and 6–59).
✓ Fragments of epithelial tissue may also be attached to the cast
matrix.
✓ Bilirubin-stained RTE cells are seen in cases of hepatitis (see
Fig. 6–59).

 Indications ✓ Casts containing RTE cells represent the presence of advanced

tubular destruction, producing urinary stasis along with disruption
of the tubular linings.
✓ Similar to RTE cells, they are associated with heavy metal and
chemical or drug-induced toxicity, viral infections, and allograft
rejection.
✓ They also accompany WBC casts in cases of pyelonephritis.

 Fatty Casts

Appearance ✓ The cast matrix may contain few or many fat droplets, and intact
oval fat bodies may be attached to the matrix (Figs. 6–60, 6–61,
6–62).
✓ Confirmation of fatty casts is performed using polarized
microscopy and Sudan III or Oil Red O fat stains.
✓ Cholesterol demonstrates characteristic Maltese cross
formations under polarized light, and triglycerides and neutral
fats stain orange with fat stains. Fats do not stain with
Sternheimer-Malbin stains.
Indications ✓ Lipiduria: seen in conjunction with oval fat bodies and free fat
droplets
✓ They are most frequently associated with the nephrotic
syndrome, but are also seen in toxic tubular necrosis, diabetes
mellitus, and crush injuries.

 Mixed Cellular Casts

Considering that a variety of cells may be present in the urinary filtrate, observing casts
containing multiple cell types is not uncommon. Mixed cellular casts most frequently
encountered include RBC and WBC casts in glomerulonephritis and WBC and RTE cell
casts, or WBC and bacterial casts in pyelonephritis. The presence of mixed elements in
a cast may make identification more difficult. Staining or phase microscopy aids in the
identification. When mixed casts are present, there should also be homogenous casts of
at least one of the cell types, and they will be the primary diagnostic marker. For
example, in glomerulonephritis, the predominant casts will be RBC, and in
pyelonephritis, the predominant casts will be WBC. Bacteria are often incorporated into
WBC casts and provide little additional diagnostic significance. Laboratory protocol
should be followed in the reporting of mixed cellular casts.

Granular Casts

Coarsely and finely granular casts are frequently seen in the urinary sediment and may
be of pathologic or non-pathologic significance. It is not considered necessary to
distinguish between coarsely and finely granular casts. Artifacts, such as clumps of
small crystals and fecal debris, may occur in shapes resembling casts and must be
differentiated.

As mentioned previously, columnar RTE cells may also resemble granular casts, and
staining for nuclear detail may be required. When granular casts remain in the tubules
for extended periods, the granules further disintegrate, and the cast matrix develops a
waxy appearance. The structure becomes more rigid, the ends of the casts may appear
jagged or broken, and the diameter becomes broader (Fig. 6–67).

 Appearance Granular casts:

✓ Seen in conjunction with WBC casts contain WBC granules of
varying sizes.
✓ Granular casts occurring as a result of cellular disintegration may
contain an occasional recognizable cell.
✓ Granular casts are easily visualized under low-power microscopy
and final identification should be performed using high power to
determine the presence of a cast matrix.
Indications ✓ Non-pathogenic conditions (appears to be from the lysosomes
excreted by RTE cells during normal metabolism)
✓ Pathogenic:
▪ Granules may represent disintegration of cellular casts
and tubule cells or protein aggregates filtered by the
glomerulus (Figs. 6–65 and 6–66).

 Waxy Casts

Appearance ✓ The brittle, highly refractive cast matrix from which these casts
derive their name is believed to be caused by degeneration of
the hyaline cast matrix and any cellular elements or granules
contained in the matrix.
✓ More easily visualized than hyaline casts because of their higher
refractive index
✓ Often appear fragmented with jagged ends and have notches in
their sides (Figs. 6–68 and 6–69).
✓ With supravital stains, waxy casts stain a homogenous, dark
pink (Fig. 6–70).
Indications Waxy casts are representative of extreme urine stasis, indicating
chronic renal failure.

Broad Casts

Often referred to as renal failure casts, broad casts like waxy casts represent extreme
urine stasis. As a mold of the distal convoluted tubules, the presence of broad casts
indicates destruction (widening) of the tubular walls. Also, when the flow of urine to the
larger collecting ducts becomes severely compromised, casts form in this area and
appear broad. All types of casts may occur in the broad form. However, considering the
accompanying urinary stasis, the most commonly seen broad casts are granular and

 waxy (Figs. 6–71 and 6–72). Bile-stained broad, waxy casts are seen as the result of
the tubular necrosis caused by viral hepatitis (Fig. 6–73).

Urine Appearanc Sources of Reporting Complete Clinical Significance

Casts e error urinalysis
correlations
Hyaline Colorless, ✓ Mucus Average ✓ Protein ✓ Glomerulonep
homogeno ✓ Fibers number ✓ Blood hritis
us matrix ✓ Hair per lpf (exercise) ✓ Pyelonephritis
✓ Increas ✓ Color ✓ Chronic renal
ed (exercise) disease
lighting ✓ Congestive
heart failure
✓ Stress
✓ Exercise
RBC Orange- ✓ RBC Average ✓ RBCs ✓ Glomerulonep
red color, clumps number ✓ Blood hritis
cast matrix per lpf ✓ Protein ✓ Strenuous
containing exercise
RBCs
WBC Cast ✓ WBC Average ✓ WBCs ✓ Pyelonephritis
matrix clumps number ✓ Protein ✓ Acute
containing per lpf ✓ Leukocyte interstitial
WBCs Esterase ✓ Nephritis

 Bacteri Bacilli ✓ Granul Average ✓ WBC ✓ Pyelonephritis

al Cast bound to ar number casts
protein casts per lpf (pyelonep
matrix hritis)
✓ WBCs
✓ LE
✓ Nitrite
✓ Protein
✓ Bacteria
Epithelia RTE cells ✓ WBC Average ✓ Protein ✓ Renal tubular
l Cell attached to cast number ✓ RTE cells damage
protein per lpf
matrix
Granular Coarse and ✓ Clumps Average ✓ Protein ✓ Glomeruloneph
fine of small number ✓ Cellular ritis
granules in crystals per lpf casts ✓ Pyelonephritis
a cast ✓ Column ✓ RBCs ✓ Stress
matrix ar ✓ WBCs ✓ Exercise
✓ RTE
cells
Waxy Highly ✓ Fibers Average ✓ Protein ✓ Stasis of urine
flow
refractile ✓ Fecal number ✓ Cellular
✓ Chronic renal
cast with material per lpf casts failure
jagged ends ✓ Granular
and notches casts
✓ WBCs
✓ RBCs
Fatty Fat droplets ✓ Fecal Average ✓ Protein ✓ Nephrotic
✓ Free fat syndrome
and oval fat debris number
droplets ✓ Toxic tubular
bodies per lpf ✓ Oval fat necrosis
bodies ✓ Diabetes
attached to
mellitus
protein ✓ Crush injuries
matrix
Broad Wider than ✓ Fecal Average ✓ Protein ✓ Extreme urine
✓ WBCs stasis
normal cast material number
✓ RBCs ✓ Renal failure
matrix ✓ Fibers per lpf ✓ Granular
casts
✓ Waxy casts