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Urinary cast

Urinary casts are microscopic, cylindrical structures formed in the distal convoluted tubules and collecting ducts of the kidney, primarily composed of Tamm-Horsfall protein (also known as uromodulin), a glycoprotein secreted by renal tubular epithelial cells, and are excreted in the urine during urinalysis.^[1]^[2]^[3] These casts reflect the functional status of the renal tubules and can incorporate various cellular elements, proteins, or other substances, serving as key diagnostic markers for kidney diseases.^[1]^[2] The formation of urinary casts occurs under conditions of low urine flow, acidic pH, and high salt concentration in the renal tubules, where Tamm-Horsfall protein aggregates and molds into the shape of the tubule lumen, potentially trapping cells, debris, or lipids during passage.^[2]^[3] In healthy individuals, casts are typically few in number and predominantly hyaline (transparent protein-based), appearing after physiologic stressors like dehydration or exercise, but their increased presence or specific compositions signal underlying pathology.^[1]^[3] Urinary casts are classified into acellular and cellular types based on their contents. Acellular casts include hyaline casts, which are the most common and consist solely of the protein matrix; granular casts, formed from degenerated cellular debris giving a "muddy brown" appearance; waxy casts, highly refractile and indicative of chronic stasis; broad casts, formed in dilated tubules and associated with chronic kidney disease; fatty casts, containing lipid droplets often seen in nephrotic syndrome; pigment casts, incorporating hemoglobin, myoglobin, or bilirubin; and crystal casts, containing crystallized substances such as uric acid.^[1]^[3]^[2] Cellular casts encompass red blood cell (RBC) casts, typically red-orange and pathognomonic for glomerulonephritis; white blood cell (WBC) casts, associated with pyelonephritis or interstitial nephritis; epithelial cell casts, derived from sloughed tubular cells in acute tubular injury; bacterial casts, linked to severe urinary tract infections; eosinophil casts, indicative of allergic or drug-induced interstitial nephritis; and mixed casts combining multiple cell types.^[1]^[3]^[2] Clinically, the detection of urinary casts via microscopic examination of a fresh urine sediment sample is essential for diagnosing renal disorders, as their type and quantity provide insights into the site and nature of kidney injury—such as glomerular bleeding (RBC casts), tubular necrosis (granular casts), or advanced chronic kidney disease (waxy casts).^[1]^[3]^[2] While a small number of hyaline casts may be normal, the presence of other casts warrants further evaluation to identify conditions like acute kidney injury, nephrotic syndrome, or infections, guiding targeted therapeutic interventions.^[1]^[3]

Introduction

Definition and composition

Urinary casts are microscopic, cylindrical structures formed in the renal tubules and collecting ducts of the kidney.^[2] They represent molds of the tubular lumens where precipitation occurs, reflecting the shape and dimensions of the nephron segments involved.^[4] Typically, these casts measure 30-50 μm in diameter, corresponding to the width of distal tubules, with lengths typically several times the diameter, ranging from 50 to several hundred micrometers depending on the site of formation and type.^[5]^[6] The primary composition of urinary casts consists of Tamm-Horsfall protein, also known as uromodulin, a glycoprotein secreted exclusively by the epithelial cells of the thick ascending limb of the loop of Henle.^[7] This protein polymerizes and gels under conditions of low urine flow, high salt concentration, and acidic pH, which promote denaturation and aggregation within the tubules.^[8] While the matrix may incorporate minor variations such as embedded proteins or lipids, the core structure excludes cellular elements in its basic form.^[4] In general morphology, urinary casts appear smooth and refractile under microscopy, featuring parallel sides, rounded or blunt ends, and a consistent cylindrical profile that distinguishes them from other urinary sediments.^[8] This uniform structure arises from the protein's gel-like solidification against the tubular walls.^[2] Urinary casts were first described in the 19th century through pioneering urinary microscopy by clinicians such as Pierre François Olive Rayer and Eugène Vigla in the late 1830s, who identified non-crystalline elements in urine sediment.^[9] The key compositional protein, uromodulin (Tamm-Horsfall protein), was isolated and characterized in 1950 by Igor Tamm and Frank L. Horsfall Jr. as a potent inhibitor of viral hemagglutination in urine.^[10]

Clinical significance in urinalysis

Urinary casts are key biomarkers in urinalysis for evaluating renal tubular and glomerular integrity, providing insights into intrarenal pathology that distinguish intrinsic kidney disease from prerenal azotemia due to hypoperfusion or postrenal obstruction from outflow issues.^[11]^[12] Their formation within the distal convoluted tubules and collecting ducts reflects conditions where urine flow is altered, allowing protein matrices to aggregate and mold cellular or acellular elements. In clinical practice, the identification of casts shifts diagnostic focus toward renal parenchymal involvement, guiding further evaluation such as serum creatinine assessment or imaging to confirm the site of injury.^[13] Even the presence of hyaline casts, the most common type, can signal reduced tubular flow or early epithelial damage, though they may appear in concentrated urine from dehydration without overt pathology.^[14] Pathologic casts, beyond hyaline, point to active renal insults like glomerulonephritis or acute tubular necrosis, where they form due to inflammation, ischemia, or toxic injury disrupting tubular homeostasis. This interpretive role in urinalysis enhances the ability to triage patients with acute kidney injury, as casts are rarely seen in non-renal causes of azotemia.^[11] Quantitatively, normal urine sediment contains 0-2 hyaline casts per low-power field (LPF), with elevations above this threshold correlating to the degree of tubular stress or damage severity.^[14]^[4] In chronic kidney disease monitoring, persistent or increasing cast counts offer prognostic utility, reflecting ongoing tubulointerstitial fibrosis and predicting faster progression to end-stage renal disease. Recent studies utilizing automated urine analyzers have quantified cast burden more precisely, linking higher loads to elevated risks of CKD advancement and cardiovascular complications in longitudinal cohorts.^[15]^[16]

Formation and detection

Pathophysiological mechanisms

Urinary casts form primarily in the distal convoluted tubule and collecting ducts of the nephron, where urine flow velocity decreases and the pH becomes more acidic, creating conditions conducive to the gelation of uromodulin.^[17] In these segments, the reduced flow allows for the concentration of proteins and solutes, facilitating the aggregation process that leads to cast development.^[18] This site-specific formation is essential, as upstream segments like the thick ascending limb primarily secrete uromodulin but do not support the stasis required for solidification.^[19] Key triggers for cast formation include urinary stasis induced by conditions such as dehydration, hypotension, or heart failure, which reduce renal perfusion and tubular flow, thereby promoting protein precipitation.^[18] High protein concentrations in the tubular fluid, often from glomerular leakage, further contribute by increasing the substrate available for aggregation.^[20] Additionally, acidic urine enhances insolubility of matrix proteins, accelerating gel formation in the low-flow environment.^[17] Uromodulin, the primary structural component of casts, is secreted as a soluble monomer by epithelial cells of the thick ascending limb and polymerizes into a gel-like matrix within the distal tubule and collecting ducts, trapping cellular debris or other elements.^[19] This polymerization is modulated by sodium concentration, where elevated levels in the tubular fluid promote microgel formation and increased viscosity, and by flow velocity, with slower rates allowing sufficient time for aggregation.^[17] The process begins with uromodulin's self-aggregation via its inter-domain linker, forming high-molecular-weight structures that stabilize under these physicochemical conditions.^[17] In pathologic states, inflammation or tubular necrosis elevates levels of matrix proteins beyond uromodulin, enhancing cast formation and contributing to obstructive nephropathy.^[20]

Methods of identification

Urinary casts are identified primarily through microscopic examination of urine sediment, requiring careful sample handling to preserve their fragile structure. Fresh urine specimens should be examined promptly, ideally within 30 to 60 minutes of collection, to minimize dissolution, particularly of cellular casts, which are sensitive to time, pH, and temperature changes.^[13] If immediate analysis is not possible, refrigeration at 4°C can extend viability up to 24 hours, though this may alter some elements.^[13] For sediment preparation, a 10-15 mL aliquot of well-mixed urine is centrifuged at 400-500 g for 5 minutes to concentrate the sediment without damaging structures, followed by decanting the supernatant and resuspending the pellet in a small volume of residual urine.^[13]^[21] Morning or first-void urine is preferred for its higher concentration, enhancing detection.^[13] Microscopic evaluation employs bright-field light microscopy at magnifications of 100-400×, with low-power fields (10× objective, 100× total) used to scan for casts and high-power fields (40× objective, 400× total) for detailed assessment.^[13] Phase-contrast microscopy is recommended to improve visibility of the translucent protein matrix in hyaline and other acellular casts, as it highlights refractile edges and internal details that may be obscured in standard bright-field illumination.^[22] Casts are typically reported quantitatively as the average number per low-power field (LPF), with findings interpreted in the context of the entire urinalysis. Stains such as Sternheimer-Malbin or Papanicolaou may occasionally be applied to enhance contrast for specific cast types, but unstained wet mounts are standard to avoid artifacts.^[23] Automated urine analyzers, such as the Sysmex UF-5000, utilize fluorescent flow cytometry or digital imaging to provide rapid preliminary screening for casts by detecting particle size, shape, and fluorescence properties, achieving throughputs up to 105 samples per hour.^[24]^[25] These systems differentiate casts from other elements like cells or crystals but require manual microscopic confirmation for accurate typing and to resolve discrepancies, as automation may under- or over-detect due to variability in cast morphology.^[26]^[27] Common pitfalls in cast identification include artifacts resembling pseudocasts, such as mucus threads, fibers, or clumped urates, which lack the uniform cylindrical shape, rounded ends, and refractile Tamm-Horsfall matrix of true casts; phase-contrast microscopy aids differentiation by revealing parallel sides and birefringence in genuine casts.^[4]^[3] Storage conditions exacerbate issues, as alkaline pH (>7.0) or dilute urine promotes rapid dissolution, while contamination from improper collection can introduce extraneous material mimicking casts.^[4]^[13] Low-speed centrifugation and immediate processing mitigate these risks, ensuring reliable detection.^[28]

Acellular casts

Hyaline casts

Hyaline casts are the most common type of acellular urinary casts, appearing as transparent, colorless, and cylindrical structures composed primarily of uromodulin (also known as Tamm-Horsfall protein), a glycoprotein secreted by the epithelial cells of the thick ascending limb of the loop of Henle.^[13]^[29] Under bright-field microscopy, they exhibit a homogeneous matrix without embedded inclusions, but they are highly refractile and more readily visible when examined using phase-contrast microscopy.^[13]^[4] In normal urine sediment, small numbers of hyaline casts—typically 0 to 2 per low-power field (LPF)—may be observed, particularly in concentrated specimens.^[30]^[11] These casts form through the gelation and polymerization of uromodulin in the distal convoluted tubules or collecting ducts, a process promoted by physiologic conditions such as low urinary flow rates, increased urine concentration, acidic pH, or stasis.^[29]^[13] This gel-like matrix molds to the shape of the renal tubules, resulting in the characteristic cylindrical form without cellular debris.^[11] Hyaline cast formation is enhanced by factors that reduce renal perfusion or increase urine osmolality, including dehydration, strenuous exercise, fever, and the use of diuretic medications.^[13]^[29] In low numbers, hyaline casts are generally benign and considered a normal physiologic finding, but elevated counts—greater than 5 per LPF—may indicate underlying pathology such as prerenal azotemia due to volume depletion or early stages of chronic kidney disease.^[29]^[30] They can also appear in association with conditions like pyelonephritis or mild heart failure, where increased plasma B-type natriuretic peptide (BNP) levels correlate with their presence even in the absence of overt renal dysfunction.^[13]^[30] Hyaline casts are distinguished from other cast types by their lack of embedded particles or cellular elements and their tendency to dissolve readily in alkaline or dilute urine, unlike more stable granular casts.^[4]^[11] This solubility underscores their proteinaceous nature and aids in confirming their identity during microscopic urinalysis.^[13]

Granular casts

Granular casts are cylindrical structures observed in urine sediment, characterized by coarse or fine yellow-brown granules embedded within a hyaline protein matrix, giving them an irregular, refractile texture that renders them less transparent than pure hyaline casts.^[13] These granules typically measure 30 to 50 micrometers in diameter and length, similar to hyaline casts, but their granular inclusions distinguish them under bright-field microscopy at 400x magnification.^[13] In cases of acute tubular injury, the granules often appear as "muddy brown" pigments, reflecting degenerated cellular debris.^[31] These casts form through the progressive degeneration of cellular elements, such as renal tubular epithelial cells or red blood cells, within the distal convoluted tubules or collecting ducts, particularly in environments of acidic pH, urinary stasis, and concentrated solutes.^[13] This process involves the breakdown of cellular casts over time, where lysosomal enzymes and metabolic byproducts contribute to the granular appearance, commonly occurring in acute tubular necrosis (ATN).^[31] The base matrix consists primarily of uromodulin (Tamm-Horsfall protein) secreted by tubular cells.^[13] Clinically, granular casts signify renal tubular epithelial damage and are associated with both acute and chronic kidney diseases, including ATN, pyelonephritis, and advanced renal failure.^[32] The presence of muddy brown granular casts is particularly indicative of ischemic or toxic ATN in acute kidney injury (AKI), helping differentiate it from prerenal azotemia.^[33] Recent research, including a 2023 study on AKI urine sediment scoring, has shown that higher counts of granular casts correlate with greater AKI severity, progression, and long-term outcomes, such as the need for renal replacement therapy, in alignment with KDIGO staging criteria.^[34]

Waxy casts

Waxy casts are acellular urinary sediment structures characterized by a homogeneous, melted wax-like appearance with a high refractive index, often featuring notched, sharp margins, and cracked or indented edges. They exhibit a broad cylindrical shape, typically wider than the diameter of renal tubules, and appear highly refractile under phase-contrast microscopy.^[35]^[13]^[36] These casts form through prolonged stasis of urine in dilated renal tubules, resulting in the homogenization and degeneration of uromodulin (Tamm-Horsfall protein), the primary protein matrix of urinary casts. This process is commonly associated with oliguria and diminished tubular flow, reflecting advanced tubular atrophy and stasis in the setting of renal failure.^[13]^[35] Clinically, waxy casts are a specific marker for chronic kidney disease or end-stage renal disease, indicating severe and longstanding renal impairment rather than acute processes. Their presence in hospitalized patients is linked to worse renal function, higher proteinuria, elevated blood pressure, and a poor prognosis, often preceding elevations in serum creatinine.^[35]^[13]^[36] A 2022 study of 1,282 patients confirmed that waxy casts have low sensitivity (0.29) but high specificity (0.97) for renal insufficiency (eGFR <60 mL/min/1.73 m²), underscoring their value as a prognostic indicator despite limited prevalence; counts exceeding 2 per low-power field are particularly alarming.^[35]

Broad casts

Broad casts represent a subtype of acellular urinary casts characterized by their markedly increased width, typically exceeding two times the diameter of standard casts (which are usually 20-50 μm wide), often measuring up to 100 μm in diameter. These casts feature a pale, homogeneous matrix that may appear waxy or granular, reflecting a composition primarily of Tamm-Horsfall protein with possible degenerative elements, and they are molded within the dilated collecting ducts of the kidney.^[37]^[4]^[38] Their formation occurs in the context of chronic tubular damage, where conditions such as prolonged urinary obstruction or vesicoureteral reflux induce tubular ectasia and stasis, enabling the development of enlarged casts from a base of hyaline or granular material. This process is facilitated by reduced urine flow and progressive renal parenchymal atrophy, distinguishing broad casts from narrower variants formed in less affected tubules.^[4]^[37] Clinically, broad casts serve as a key indicator of advanced chronic renal pathology, particularly chronic renal failure, where they correlate with significantly reduced glomerular filtration rate (GFR) and end-stage kidney disease. They are also associated with chronic pyelonephritis, characterized by recurrent infections leading to tubular dilation, and analgesic nephropathy, a tubulointerstitial disorder from prolonged analgesic use that promotes chronic obstruction and ectasia.^[36]^[39]30873-4/fulltext) Recent post-2020 studies emphasize the role of broad casts in urine sediment analysis for monitoring chronic kidney disease (CKD) progression, with automated urinalysis systems showing potential for earlier detection despite challenges in cast identification accuracy compared to manual microscopy. These casts may share a waxy appearance with standard waxy casts but are specifically linked to dilated tubular origins.^[36]^[40]

Fatty casts

Fatty casts are cylindrical structures composed of a proteinaceous matrix, typically hyaline or granular, embedded with numerous refractile lipid globules that appear oval or round and impart a yellow-white hue under bright-field microscopy. These globules, often derived from cholesterol esters or triglycerides, exhibit a distinctive Maltese cross birefringence when viewed under polarized light, aiding in their identification.^[4]^[3] Formation occurs primarily in the distal convoluted tubules or collecting ducts, where free lipids from glomerular filtration—stemming from podocyte injury and subsequent lipiduria—adhere to and become incorporated into the uromodulin (Tamm-Horsfall protein) matrix during cast precipitation. This embedding is facilitated by tubular degeneration and impaired lipid reabsorption, commonly in the context of heavy proteinuria and hyperlipidemia, with optimal stability in neutral to alkaline urine pH.^[13]^[41]^[4] Clinically, fatty casts are a hallmark of nephrotic syndrome, reflecting severe glomerular damage with lipid nephrosis and elevated urinary cholesterol esters, and are also seen in diabetes mellitus, hypothyroidism, acute tubular necrosis, and post-traumatic crush injuries. Their presence signifies advanced renal pathology involving lipid dysregulation and proteinuria exceeding 3.5 g/day.^[42]^[13] Diagnosis is confirmed by applying Sudan III or Oil Red O stain, which imparts a red-orange color to the lipid inclusions, thereby distinguishing fatty casts from unbound free lipid droplets in the urine sediment. Polarized light microscopy further enhances detection of the Maltese cross pattern without additional staining.^[36]^[43]

Pigment casts

Pigment casts are cylindrical structures formed in the renal tubules by the aggregation of heme pigments or bilirubin within a matrix of uromodulin (Tamm-Horsfall protein), appearing as reddish-brown for hemoglobin or myoglobin variants and yellow to green-black for bilirubin types, often with a granular or homogeneous texture embedded in a hyaline matrix.^[44]^[45] These casts are visible under microscopy in urine sediment and may resemble granular casts in their textured appearance but are distinguished by their pigment content.^[46] Formation occurs when filtered pigments from plasma bind to uromodulin in the distal tubules, particularly under conditions of low urine pH that promote precipitation and cast assembly. In cases of intravascular hemolysis, free hemoglobin is released, overwhelms haptoglobin binding, and passes through the glomerulus to form casts; similarly, myoglobin from muscle breakdown in rhabdomyolysis precipitates in acidic environments, while bilirubin in severe jaundice conjugates and filters excessively, leading to bile salt aggregation.^[47]^[48] This process is exacerbated in obstructive or toxic states, contributing to tubular obstruction.^[45] Clinically, hemoglobin casts are associated with hemolytic anemias such as autoimmune hemolytic anemia or paroxysmal nocturnal hemoglobinuria, often resulting in acute kidney injury (AKI) with elevated serum creatinine. Myoglobin casts predominate in rhabdomyolysis from crush injuries or trauma, signaling tubular toxicity and AKI through oxidative stress and obstruction. Bilirubin casts arise in hepatic failure or decompensated cirrhosis with severe hyperbilirubinemia, where direct bilirubin levels exceed 20 mg/dL, promoting mitochondrial damage and acute tubular necrosis.^[47]^[46]55928-0/fulltext) All types indicate pigment-induced nephrotoxicity, with many patients recovering renal function upon addressing the underlying cause.^[47] Recent 2024 reviews emphasize the specificity of myoglobin casts in predicting AKI post-trauma, as their presence correlates with serum myoglobin levels above 3865 μg/L, offering superior prognostic value over creatine kinase for risk stratification and hemodialysis needs in rhabdomyolysis.^[48]

Crystal casts

Crystal casts are uncommon formations in urine sediment consisting of a proteinaceous matrix, primarily uromodulin (also known as Tamm-Horsfall protein), embedded with precipitated crystals derived from supersaturated urinary solutes. These casts appear as cylindrical structures with irregular, crystalline inclusions that vary in shape, size, and color based on the crystal type; for instance, uric acid crystals often present as needle-like or rhombic forms within the matrix, while oxalate crystals may appear as envelope-shaped or sheaves. The overall morphology can resemble granular casts but is distinguished by the birefringent, defined crystalline elements visible under polarized light microscopy. Formation of crystal casts occurs when urine becomes supersaturated with crystallizable substances, leading to precipitation within the gel-like uromodulin matrix secreted by renal tubular epithelial cells in the distal nephron. This process is frequently triggered by conditions such as dehydration, which concentrates urine solutes, or by metabolic derangements and medications that alter solubility; crystal precipitation is highly pH-dependent, with acidic urine (pH <5.5) promoting uric acid crystal formation and alkaline urine favoring struvite (triple phosphate) crystals. The uromodulin matrix provides a scaffold for crystal entrapment during cast solidification in the renal tubules under low flow or stagnant conditions. Clinically, crystal casts are indicative of crystal-induced acute kidney injury (AKI) and are associated with intrarenal crystal deposition causing tubular obstruction and inflammation. Uric acid crystal casts are particularly linked to tumor lysis syndrome following chemotherapy or gout flares, where rapid nucleic acid breakdown elevates serum urate levels, leading to urinary supersaturation. Oxalate crystal casts occur in hyperoxaluria, such as from excessive dietary intake (e.g., high-oxalate foods like nuts or vitamin C supplements), resulting in AKI with tubular oxalosis confirmed by biopsy. Drug-induced examples include sulfonamide antibiotics (e.g., sulfamethoxazole), which form needle- or fan-shaped crystals in acidic urine, precipitating AKI through tubular blockade. Cystine crystal casts, appearing as hexagonal plates, are seen in cystinuria, an inherited disorder of renal amino acid transport causing recurrent nephrolithiasis and potential AKI. Due to their scarcity, crystal casts are infrequently observed and can occasionally represent artifacts from sample cooling or contamination, necessitating correlation with urine chemistry (e.g., pH, specific gravity, solute levels) and, if applicable, renal stone composition analysis for confirmation. Their detection underscores the value of fresh urine sediment examination to distinguish true pathologic findings from in vitro formations.

Cellular casts

Red blood cell casts

Red blood cell (RBC) casts are cylindrical structures formed by red blood cells embedded within a Tamm-Horsfall mucoprotein matrix, typically appearing as red-brown or reddish cylinders under phase-contrast microscopy, with intact or fragmented RBCs. These casts are distinguished from free RBCs or other cast types by their uniform shape and the presence of embedded erythrocytes, which may show varying degrees of preservation depending on the duration in the urinary tract.^[4]^[11] RBC casts form when bleeding originates from the glomeruli, allowing erythrocytes to pass through damaged glomerular basement membranes into the tubular lumen, where they become trapped in the uromodulin-rich protein precipitate during periods of urinary stasis in the distal tubules or collecting ducts. This process requires both glomerular injury to release RBCs and sufficient intratubular protein for matrix formation, often exacerbated by reduced urine flow. Once formed, the casts maintain their shape as they are flushed into the urine, though prolonged exposure can lead to partial degradation of the RBCs.^[4]^[49] The presence of RBC casts is pathognomonic for glomerular diseases, particularly proliferative glomerulonephritides such as IgA nephropathy, lupus nephritis, post-streptococcal glomerulonephritis, and anti-glomerular basement membrane disease, as well as renal vasculitis; the presence of RBC casts is highly specific for active glomerular inflammation. These casts indicate disruption of the glomerular filtration barrier, often accompanied by hematuria exceeding 5 RBCs per high-power field and dysmorphic features in the erythrocytes.^[50]^[49]^[11] Dysmorphic RBCs within these casts, characterized by irregular shapes such as acanthocytes (bleb-protruding, ring-like forms), are a hallmark of glomerular origin, distinguishing them from isomorphic RBCs seen in lower urinary tract bleeding; acanthocytes constitute at least 5-20% of RBCs in glomerular hematuria and result from mechanical distortion as cells traverse damaged glomerular structures. This dysmorphism enhances diagnostic specificity, with studies showing that the combination of dysmorphic RBCs and RBC casts has a sensitivity of 52-100% and specificity up to 98% for confirming glomerulonephritis.^[50]^[49]^[51]

White blood cell casts

White blood cell casts, also known as leukocytic casts, are cylindrical structures composed of embedded white blood cells, predominantly neutrophils, within a protein matrix formed in the distal renal tubules or collecting ducts.^[4] Under light microscopy, they typically appear as pale yellow, granular tubes measuring 30-50 μm in diameter and up to several hundred micrometers in length, with the leukocytes often showing degenerate nuclei that obscure cellular detail, distinguishing them from free-floating white blood cells.^[4]^[13] These casts form during episodes of tubulointerstitial inflammation, where white blood cells infiltrate the renal interstitium and are released into the tubular lumen, adhering to and becoming embedded in the Tamm-Horsfall mucoprotein secreted by tubular epithelial cells, especially under conditions of urinary stasis or low flow rates that promote matrix solidification.^[13]^[4] Pyuria, characterized by the presence of free white blood cells in the urine, commonly accompanies their formation as part of the broader inflammatory response.^[52] White blood cell casts are strongly associated with acute infectious or inflammatory processes confined to the kidney, including acute pyelonephritis, acute interstitial nephritis, and renal papillary necrosis.^[1]^[37] In allergic or drug-induced interstitial nephritis, variants containing eosinophils may predominate, reflecting an eosinophilic inflammatory component.^[53] In urine sediment examination, the detection of more than one white blood cell cast per low-power field (LPF) is indicative of an intrarenal source of inflammation or infection, helping to differentiate true renal pathology from contamination or lower urinary tract issues.^[54]^[4]

Epithelial cell casts

Epithelial cell casts, also referred to as renal tubular epithelial cell (RTE) casts, consist of sloughed renal tubular epithelial cells embedded within a proteinaceous matrix, primarily composed of Tamm-Horsfall mucoprotein. Under microscopy, these casts appear as cylindrical structures with parallel sides containing clusters or sheets of rounded RTE cells; the cells are larger than leukocytes or erythrocytes, exhibit granular cytoplasm, and possess eccentric nuclei that may become obscured in degenerated forms.^[4] These casts form through the detachment of RTE cells from the tubular lining due to injury mechanisms such as necrosis or ischemia, allowing the cells to aggregate within the tubular lumen and mold into casts under the influence of urine flow and protein precipitation. They can originate from either proximal or distal tubules, though proximal tubule-derived casts are more commonly linked to severe ischemic or toxic insults, while distal ones may reflect broader tubular damage.^[13] Clinically, epithelial cell casts signify significant renal tubular injury and are associated with conditions including acute tubular necrosis (ATN), renal transplant rejection, and exposure to nephrotoxins like heavy metals or certain drugs. Their presence often correlates with granular casts, which arise from the degeneration of these cellular elements.^[55] Identification of RTE cells in casts requires differentiation from other epithelial elements, such as transitional cells from the bladder, achieved by noting the smaller size, rounder morphology, and increased cytoplasmic granularity of RTE cells compared to the larger, dome-shaped transitional cells.^[4]

Bacterial casts

Bacterial casts are rare urinary sediment findings characterized by the presence of bacteria, typically in the form of rods or cocci, embedded within a proteinaceous matrix, often appearing irregular and granular under microscopy. These casts may contain densely packed, diffusely scattered, or clustered bacterial elements within a hyaline-like structure and are frequently accompanied by white blood cells, reflecting concurrent inflammation.^[36] They form in the distal convoluted tubules and collecting ducts during episodes of heavy bacteriuria associated with renal parenchymal infection, where bacteria are entrapped in the gel-like polymerized uromodulin (Tamm-Horsfall protein) matrix as it precipitates under acidic or concentrated urine conditions.^[36] This process is facilitated by the increased uromodulin secretion and gel formation in response to tubular injury from ascending bacterial invasion. Clinically, bacterial casts are highly specific indicators of acute pyelonephritis, signaling severe upper urinary tract involvement such as complicated infections or renal abscesses, often resulting from ascending pathogens like Escherichia coli.^[56] Their detection necessitates correlation with urine culture to identify the causative organism and guide antibiotic therapy, as they distinguish renal infection from lower tract involvement.^[56]^[57] In immunocompromised patients, such as those with diabetes or undergoing chemotherapy, bacterial casts underscore the need for prompt evaluation, with 2024 reviews emphasizing the role of imaging modalities like contrast-enhanced CT to confirm renal parenchymal involvement and detect complications like abscesses.^[36]^[58]

Eosinophil casts

Eosinophil casts are cylindrical structures observed in urine sediment, composed of a protein matrix embedding eosinophils, which are identifiable by their characteristic bilobed nuclei and prominent cytoplasmic granules.^[13] Under bright-field microscopy, these casts appear as elongated forms with embedded cells; when stained with Wright's or Hansel's stain, the eosinophil granules exhibit an orange-red coloration, facilitating their distinction from other cellular elements.^[59] Hansel's stain, a combination of eosin and methylene blue, is particularly effective for highlighting these granules in bright orange, enhancing detection in urinary sediment.^[60] These casts form in the distal renal tubules and collecting ducts during periods of acute inflammation, where Tamm-Horsfall mucoprotein precipitates to create the matrix, trapping eosinophils that have migrated from the renal interstitium into the tubular lumen.^[4] In allergic or hypersensitivity reactions, cytokines such as interleukin-5 recruit eosinophils to the kidney interstitium, and during intense inflammation, these cells spill into the tubules, becoming incorporated into the forming casts.^[61] Clinically, eosinophil casts are most strongly associated with drug-induced acute interstitial nephritis (AIN), often triggered by medications such as antibiotics (e.g., penicillins, cephalosporins) or nonsteroidal anti-inflammatory drugs (NSAIDs).^[62] They may also appear in parasitic infections involving the urinary tract or kidneys, where eosinophilic infiltration occurs as part of the immune response.^[63] Confirmation of eosinophil presence in casts typically requires special staining like Hansel's method on fresh urine sediment.^[64] The diagnostic value of eosinophil casts lies in their support for AIN, particularly when eosinophils constitute more than 1% of urinary leukocytes in sediment analysis, though this finding has moderate sensitivity (around 30-60%) and specificity (approximately 70%).^[65] Their presence, alongside eosinophiluria, strengthens suspicion for hypersensitivity-mediated renal injury but is not pathognomonic, as they can occasionally occur in other inflammatory renal conditions.^[66]

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Igor Tamm and Frank Horsfall Jr., who initially discovered this protein in 1950 as an inhibitor of viral hemagglutination in the urine. This protein was ...
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A practical approach to the pathology of renal intratubular casts
Light chain cast formation is further influenced by additional factors including uromodulin concentrations, ionic composition of the tubule fluid, tubule ...
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[PDF] Urine Sediment Guide | Idexx
Centrifuge the sample (and a balance tube) on the Urine setting (or 400 g). Note: If your centrifuge does not have a Urine setting, refer to its operator's ...
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Oct 1, 2018 · Phase contrast microscopy (PCM) is the recommended technique for manual urinary sediment (U-sed) examination. In fact, compared to bright field microscopy (BFM ...
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Casts from freshly voided urine specimens, cytocentrifuged and stained by the Papanicolaou method, can be visualized optimally from permanent slide preparations ...Missing: urinalysis | Show results with:urinalysis
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Fully automated analyzer that uses Fluorescent Flow Cytometry technology for accurate and precise urine particle differentiation and counts.
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https://www.sysmex.com/en-us/lab-solutions/urinalysis/un-series/uf-5000
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Sysmex UF-5000 Automatic Urine Sediment Analyzer Can Improve ...
The aim of this study was to evaluate the consistency and accuracy of all the parameters of the urine samples detected by two automated urine sediment ...
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Comparison of IDEXX SediVue Dx® urine sediment analyzer to ...
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Apr 18, 2023 · A relative centrifugal force (RCF) of less than 400 appears to be optimal to generate sediment without damaging urinary elements [7].
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Aug 8, 2025 · Histologic findings may include proximal tubular damage, tubular dilation, and characteristic muddy brown granular casts on urinalysis.Missing: staging | Show results with:staging
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Acute kidney injury (AKI) is an abrupt decrease in kidney function that occurs over a period of 7 days or less, and chronic kidney disease (CKD) is defined as a ...<|control11|><|separator|>
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Jun 22, 2022 · In conclusion, waxy or pre-waxy casts in urinary sediment are closely related to impaired renal function and are indicators of renal injury.
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The factors which favor protein cast formation are low flow rate, high salt concentration, and low pH, all of which favor protein denaturation and ...
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May 22, 2023 · Analgesic nephropathy is chronic tubulointerstitial nephritis caused by chronic use of analgesics such as acetaminophen, aspirin, and nonsteroidal anti- ...
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Diagnostic Utility of Urine Microscopy in Kidney Diseases
May 28, 2024 · Homogenous, broad, waxy-appearing cast with high refractile index. ... They can also be elevated in other conditions such as sepsis, chronic ...
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Urine Sediment of the Month: Isolated Lipiduria
Nov 11, 2020 · No oval fat bodies or lipid casts, signs of glomerular hematuria or tubular injury were present ... lipiduria as a sign of podocyte injury.
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Sudan III has long been used, to a limited extent, for the identification of fat in the urine.2 Since the presence of fat in casts or cells in the urinary ...
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A practical approach to the pathology of renal intratubular casts
This review discusses the clinicopathologic characteristics of the six most common pathologic casts: light chain, hemoglobin, myoglobin, red cell, neutrophilic ...
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### Summary of Bile Cast Nephropathy
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Hemolysis-associated hemoglobin cast nephropathy results from a ...
Intravascular hemolysis is relatively rare but can lead to acute kidney injury (AKI), from increased destruction of erythrocytes and release of free hemoglobin.
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The acanthocytes, dysmorphic red blood cells, and RBC casts are pathognomonic of glomerular inflammation. It can be identified in urine analysis. Supportive ...
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Oct 6, 2017 · Dysmorphic red blood cells (dRBCs) on urine microscopy have been associated with glomerulonephritis (GN). We assessed the prevalence and ability of dRBCs to ...
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Urine Sediment Exam Provides More Diagnostic Information in AKI ...
Urine sediment score: one for zero casts per LPF and zero RTECs per HPF; two for one to five casts per LPF ... The observation of white blood cell casts ...
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The presence and number of renal tubular epithelial cells and renal tubular epithelial cell casts and/or granular casts in the urine sediment appear beneficial ...
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This cast is characterized by the presence of bacteria in its matrix and appears to be specific for and diagnostic of pyelonephritis. It is easily demonstrated ...
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A variety of clinical conditions were associated with eosinophiluria. Urinary tract infection and acute interstitial nephritis were most common, each accounting ...
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Infection of the upper and lower urinary tract accounted for 45% of the clinical conditions associated with eosinophiluria. In nine (14%) of the 65 patients a ...
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Eosinophiluria - PubMed
Eosinophiluria demonstrated by Hansel's stain appears to be a sensitive marker for drug-induced acute interstitial nephritis.
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Sep 19, 2013 · Urine eosinophils (UEs) have been shown to correlate with acute interstitial nephritis (AIN) but the four largest series that investigated ...