Casts in the Urine Sediment

왗your lab focus 왘
interpretation [cytology]
Casts in the Urine Sediment
Karen M. Ringsrud, MT(ASCP)
From the Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN
왘
Casts in the urine sediment and
their disease associations
왘
Cast origins or mechanisms of
formation
왘
Reagent-strip findings or other
sediment findings associated with
casts
Casts are the result of solidification
of material (protein) in the lumen of the
kidney tubules, more specifically in the
nephron. Once formed, these molds (or
casts) of the tubule are eliminated via the
urine and may be seen in the urine sediment. Such structures are extremely important clinically, as they show the
conditions in the nephron where they
were formed. They may be considered to
represent a biopsy of the kidney. If a cast
is seen in the urine, kidney disease or involvement exists; the presence of casts
indicates kidney (renal) disease rather
than lower urinary tract disease.
All casts have a matrix of TammHorsfall mucoprotein to which other proteins or elements may be added. They are
generally associated with a positive
reagent-strip test result for protein. They
may contain RBCs, WBCs, renal epithelial cells, fat globules, bacteria, and degenerated forms of any of these structures,
which are seen as granules. Aggregates of
plasma proteins, including fibrinogen, immune complexes, and globulins, may also
be seen as granules within a cast. Although
size and diameter vary, casts are generally
cylindrical structures that have a definite
outline, showing parallel sides and 2
rounded ends. They are approximately 7
or 8 times the diameter of an RBC and
several times longer than wide. Casts are
classified primarily on the basis of morphologic features; various types have different clinical implications.
Hyaline Casts
Hyaline casts are both the most difficult to visualize and least important type
of casts encountered in the urine
sediment. They are the result of solidification of Tamm-Horsfall mucoprotein,
which is secreted by the renal tubular
cells, and they may be present without
significant proteinuria. A few may be seen
in the urine of healthy persons. They may
be seen in increased numbers after strenuous exercise and in some renal diseases.
Cellular Casts
A cellular cast may be composed of
any of the cells found in the urine
sediment, such as RBC, WBC, or renal
tubular epithelial cell. Bacterial cell casts
have also been described as have casts
consisting of a mixture of cell types. The
cellular cast appears to result from a
clumping, or conglutination, of cells that
are incorporated in a protein matrix. In
some instances, a few cells are found embedded in a hyaline matrix. If a cellular
cast is seen in the urine, it is known that
the cells were present in the kidney
(nephron). Although causes and severity
differ, the presence of cellular casts indicates a disease process. It may be difficult
or impossible to determine what cell type
is present in a cast, because the cells are
subject to deterioration. Such casts are
generally reported as “cellular casts,” and
the cell type is generally suggested by
other findings in the urine sediment.
RBC Casts
RBCs may be found in a cast either as
the result of leakage of RBCs through the
glomerular membrane or by bleeding into
the tubules at any point along the nephron
[I1]. According to Rose and Rennke,1 “Red
cell casts . . . are virtually diagnostic of
some form of glomerulonephritis or vasculitis.” RBC casts are most often associated
with diseases that affect the glomerulus,
such as acute poststreptococcal glomerulonephtitis and other acute glomerulonephritides, IgA nephropathy, and lupus
nephritis. They may also be seen in cases of
©
laboratorymedicine> april 2001> number 4> volume 32
[I1] RBC cast. RBC casts are particularly fragile
and prone to disintegration (×400).
subacute bacterial endocarditis, renal infarction, and rarely in severe pyelonephritis
(tubulointersititial disease).
Other forms of RBC casts include
blood casts and hemoglobin casts, which
are the result of degeneration of RBCs
within the cast matrix. The cells are no
longer visible, yet the remaining hemoglobin pigment imparts a characteristic
orange-yellow or red-brown color, which
distinguishes them from waxy casts. This
breakdown of cells within the cast suggests urinary stasis and a condition more
chronic than acute. Reagent-strip findings
associated with RBC casts are positive
test results for protein and blood.
WBC Casts
WBC casts are generally composed
of neutrophils. Theoretically, they may
enter the nephron at any point, but they
are generally associated with tubulointerstitial disease such as acute pyelonephritis. In this case, they are associated with
the presence of WBCs and bacteria in the
urine sediment; the occurrence of WBC
casts locates an infection within the kidney rather than the lower urinary tract.
Occasionally, the WBCs enter the urine at
the glomerulus, and WBC casts or mixed
RBC and WBC casts may be seen in
cases of acute glomerulonephritis. They
may also be seen in acute interstitial
191
왗your lab focus 왘
nephritis, lupus nephritis, and acute papillary necrosis.
Reagent-strip findings associated
with WBC casts are positive test results
for protein, leukocyte esterase, and nitrite
(if certain bacteria are present).
Bacterial Casts
Bacterial casts are casts composed of
bacteria in a protein (hyaline) matrix. The
bacteria might be closely packed,
diffusely scattered, or concentrated in an
area of the cast; WBCs are also frequently
present. Bacterial casts may be misidentified as granular or cellular casts. They
may be identified by Gram staining the
dried (cytocentrifuged) sediment. Bacterial casts are diagnostic of acute
pyelonephritis or intrinsic renal infection.
Epithelial Casts
Epithelial casts are composed of renal
epithelial cells [I2]. A serious pathologic
finding, epithelial casts are associated
with acute tubular necrosis, viral disease
such as infection with cytomegalovirus,
and exposure to nephrotoxic substances
such as mercury, ethylene glycol, and various drugs (the same conditions associated
with renal epithelial cells). They may be
difficult to distinguish from WBC casts,
especially as they begin to degenerate into
granular casts. Other sediment findings
and clinical symptoms are helpful.
Reagent strips show positive reactions for
protein, but test results for leukocyte esterase are negative unless sufficient neutrophils are also present.
192
Granular Casts
Granular casts are generally the result
of degeneration of cells in cellular casts
[I3]. Their significance lies with the cast
from which they were formed. Granular
casts may also be the result of direct aggregation of serum proteins and other substances into a matrix of Tamm-Horsfall
mucoprotein. In general, the presence of
granular casts suggests stasis in the
nephron. The casts are associated with
tubulointerstitial disease.
Waxy Casts
Waxy casts represent the final stage
in the degeneration of cells within a
a
[I2] Epithelial cell cast (Sedi-Stain, ×400).
b
[I4] a, Fatty cast and dysmorphic RBC (arrow)
(×400). b, Same fatty cast as in image 4a
viewed with polarized light, showing the
Maltese cross appearance of cholesterol
(×400).
A
B
[I3] Waxy cast (A) and cellular-to-granular cast
(B) (×100.)
cast—from cellular to granular to waxy
[I3]. They suggest renal stasis or
nephron obstruction and represent serious disease. Associated with severe
chronic renal disease and renal amyloidosis, waxy casts are only rarely seen in
acute renal disease. They are often seen
as broad casts (having a greater diameter
than most casts). Such casts probably
form in the larger collecting tubules or
dilated tubules where they are able to
form when there is significant stasis and
tubular atrophy. For this reason, they
have been referred to as renal failure
casts.
Waxy casts are homogeneous, like
hyaline casts, but they are more refractile, with sharper outlines, and they tend
to have broken or blunt ends and fissures
or cracks along the sides. It is important
that waxy casts not be confused with
fibers from disposable diapers or other
contaminants. The presence of protein
on the reagent strip and lack of polarization of the waxy cast with polarized
light help with this distinction.
laboratorymedicine> april 2001> number 4> volume 32
©
Fatty Casts
Fatty casts contain globules of fat,
either as triglyceride or neutral fat,
which stains with fat stains, or as cholesterol, which will polarize as a Maltese
cross [I4a, I4b]. Fatty casts are associated with oval fat bodies and free fat and
with massive proteinuria (300 mg/dL
[3g/L] or more on reagent strips). The
fatty cast may contain free globules of
fat or oval fat bodies. These findings are
associated with the nephrotic syndrome.
Fatty casts may also be found in patients
with diabetic nephropathy or toxic renal
poisoning.
Other Casts
There are a variety of other casts
that may or may not be of clinical significance. Myoglobin casts are of clinical importance because they occur with
myoglobinuria as a result of acute muscle damage, which may result in acute
renal failure. They appear much like a
hemoglobin cast, but they are dark red to
brown because of the myoglobin
pigment. Associated findings in the urinalysis are a positive reagent-strip test
for “blood” (actually myoglobin) without the presence of RBCs in the
sediment.
Casts may also be stained with
bilirubin or intensely colored drugs such
as phenazopyridine. Such staining is
helpful in the microscopic visualization
of these casts. Hemosiderin casts may be
seen in the urine sediment 2 or 3 days
after an acute hemolytic episode. The
왗your lab focus 왘
Suggested Reading
College of American Pathologists. Surveys
Hematology Glossary. Northfield, IL: College
of American Pathologists; 1999.
Haber MH. Urinary Sediment: A Textbook
Atlas. Chicago, IL: ASCP Press; 1981.
Henry JB, Lauzon RL, Schumann GB. Basic
examination of urine. In: Henry JB, ed.
Clinical Diagnosis and Management by
Laboratory Methods. 19th ed. Philadelphia,
PA: Saunders; 1996.
Linné JJ, Ringsrud KM. Clinical Laboratory
Science: The Basics and Routine Techniques.
4th ed. St Louis, MO: Mosby; 1999.
Ringsrud KM, Linné JJ. Urinalysis and Body
Fluids: A ColorText and Atlas. St Louis, MO:
Mosby; 1995.
왘
Practice parameters, including
standards, practice guidelines, and
options, directing clinical decision
making
왘
Rationales for practice parameters
왘
How practice parameters are
developed
왘
The effectiveness of practice
parameters and barriers to their
acceptance
coarse yellow-brown granules of hemosiderin stain blue with a Prussian blue
stain for iron. Hemosiderin granules may
also be seen in the urine sediment, either
free or within macrophages or renal epithelial cells, as the result of intravascular
hemolysis.
Finally, crystal casts of various urinary crystals have been described. There
is disagreement about whether they are
casts or merely crystals adhering to a
cast form or artifacts. The clinical significance is that of the crystal in question.
of casts of all types indicates renal involvement. Casts represent different disease states; eg, RBC casts are most
associated with glomerular disease,
whereas WBC casts are indicative of
tubular disease, especially infection and
acute pyelonephritis. Casts must be
properly identified so that meaningful
diagnoses can be made.
1. Rose BD, Rennke HG. Renal Pathophysiology—
The Essentials. Baltimore, MD: Williams &
Wilkins; 1994:200.
Conclusion
Casts in the urine sediment have
various origins or mechanisms of formation and clinical relevance. The presence
193
©
laboratorymedicine> april 2001> number 4> volume 32