your lab focus 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
Casts in the urine sediment and their disease associations Cast origins or mechanisms of formation 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

[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

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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. 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

[I2] Epithelial cell cast (Sedi-Stain, 400).

[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
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

B
[I3] Waxy cast (A) and cellular-to-granular cast (B) (100.)

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castfrom 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.

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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. Conclusion Casts in the urine sediment have various origins or mechanisms of formation and clinical relevance. The presence 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.

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. Linn JJ, Ringsrud KM. Clinical Laboratory Science: The Basics and Routine Techniques. 4th ed. St Louis, MO: Mosby; 1999. Ringsrud KM, Linn JJ. Urinalysis and Body Fluids: A ColorText and Atlas. St Louis, MO: Mosby; 1995.