Urinary casts

Overview
‘Cast’ describes the shape of aggregated particulates in urine rather than a particular substance, thus a modifier is necessary to describe the actual composition of the cast. ‘Cast’ simply describes a cylindrically shaped aggregation of some particulate that forms in the distal convoluted tubule or distal nephron via precipitation of a mucoprotein secreted by tubule cells (Tamm-Horsfall protein) or, in proteinuria and to a lesser extent, albumin. Cast formation is pronounced in environments favoring protein denaturation and precipitation (low flow, concentrated salts, low pH). Unfortunately, Tamm-Horsfall protein is particularly susceptible to precipitation in these conditions.

When present on microscopic evaluation during urinalysis, urinary casts hold significance as diagnostic and prognostic indicators of kidney disease. As reflected in their cylindrical form, casts are generated in the small tubules and collecting ducts of the kidney, and generally maintain their shape and composition as they pass the lower conveyances of the urinary system. Although the commonest forms are benign, other forms are indicative of a pathologic state. All rely on the inclusion or adhesion of various elements on a mucoprotein base – the hyaline cast. The various types of casts that can be found in urine sediment may be classified as follows:

Hyaline casts
The most common type of cast, hyaline casts are solidified Tamm-Horsfall mucoprotein secreted from the tubular epithelial cells of individual nephrons. Low urine flow, concentrated urine, or an acidic environment can contribute to the formation of hyaline casts, and as such, they may be seen in normal individuals in dehydration or vigorous exercise. Hyaline casts are cylindrical and clear, with a low refractive index, so that they can easily be missed on cursory review under brightfield microscopy, or on an aged sample where dissolution has occurred. On the other hand, phase contrast microscopy leads to easier identification. Given the ubiquitous presence of Tamm-Horsfall protein, other cast types are formed via the inclusion or adhesion of other elements to the hyaline base.

Granular casts
The 2nd most common type of cast, granular casts can result either from the breakdown of cellular casts, or the inclusion of aggregates of plasma proteins (eg, albumin) or immunoglobulin light chains. Depending on the size of inclusions, they can be classified as fine or coarse, though the distinction has no diagnostic significance. Their appearance is generally more cigar-shaped and of a higher refractive index than hyaline casts.

Waxy casts
Thought to represent the end product of cast evolution, waxy casts suggest the very low urine flow associated with severe, longstanding kidney disease such as renal failure. Additionally, due to urine stasis and their formation in diseased, dilated ducts, these casts are significantly larger than hyaline casts. While cylindrical, they also possess a higher refractive index and are more rigid, demonstrating sharp edges, fractures, and broken off ends. Waxy casts also fall under the umbrella of “broad” casts, a more general term to describe the wider cast product of a dilated duct.

Fatty casts
Formed by the breakdown of lipid rich epithelial cells, these are hyaline casts with fat globule inclusions, and are yellowish-tan in appearance. If cholesterol or cholesterol esters are present, they are associated with the “Maltese cross” sign under polarized light. They can be present in various disorders, including the high urinary protein nephrotic syndrome, diabetic or lupus nephropathy, or larger scale necrosis or epithelial cell death.

Pigment casts
Formed by the adhesion of metabolic breakdown products or drug pigments, these casts are so named due to their discoloration. Pigments include those produced endogenously, such as hemoglobin in hemolytic anemia, myoglobin in rhabdomyolysis, and bilirubin in liver disease. Drug pigments, such as phenazopyridine, may also cause cast discoloration.

Crystal casts
Though crystallized urinary solutes, such as oxalates, urates, or sulfonamides, may become enmeshed within a hyaline cast during its formation, the clinical significance of this occurrence is not felt to be great.

Red blood cell casts
The presence of red blood cells within the cast is always pathologic, and is strongly indicative of glomerular damage, which can occur in glomerulonephritis from various causes or vasculitis, including Wegener's granulomatosis, systemic lupus erythematosis, poststreptococcal glomerulonephritis or Goodpasture’s syndrome. They can also be associated with renal infarction and subacute bacterial endocarditis. They are a yellowish-brown color, and generally cylindrical with sometimes ragged edges; their fragility makes inspection of a fresh sample paramount. They are usually associated with nephritic syndromes.

White blood cell casts
Indicative of inflammation or infection, the presence of white blood cells within or upon casts strongly suggests pyelonephritis, a direct infection of the kidney. They may also be seen in inflammatory states, such as acute allergic interstitial nephritis, nephrotic syndrome, or post-streptococcal acute glomerulonephritis. White cells sometimes can be difficult to discern from epithelial cells, and may require special staining. Differentiation from simple clumps of white cells can be made by the presence of hyaline matrix.

Bacterial casts
Given their appearance in pyelonephritis, these should be seen in association with loose bacteria, white blood cells, and white blood cell casts. Their discovery is likely rare, due to the infection fighting efficiency of neutrophils, and the possibly of misidentification as a fine granular cast.

Epithelial cell casts
Formed via inclusion or adhering of desquamated epithelial cells of the tubule lining. Cells can adhere in random order or in sheets, and are distinguished by large, round nuclei and a lower amount of cytoplasm. These can be seen in acute tubular necrosis and toxic ingestion, such as from mercury, diethylene glycol, or salicylate. In each case, clumps or sheets of cells may slough off simultaneously, depending of the focality of injury. Cytomegalovirus and viral hepatitis are organisms that can cause epithelial cell death as well.

Reference
Haber, Meryl H. Urinary Sediment: A Textbook Atlas. American Society of Clinical Pathologists, Chicago. 1981.