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Coarse, deeply-pigmented granular casts (ie, "muddy brown" or heme-granular casts) are considered characteristic of ATN, the leading cause of acute kidney injury (AKI) in hospitalized patients [56].
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lar casts or the aggregation of proteins within a cast matrix [2] (picture 9). Granular casts may be coarse or fine in nature, although the clinical significance of this distinction is unclear. <span>Coarse, deeply-pigmented granular casts (ie, "muddy brown" or heme-granular casts) are considered characteristic of ATN, the leading cause of acute kidney injury (AKI) in hospitalized patients [56]. In patients with ischemic or toxic injury to the tubular epithelial cells, cell sloughing into the tubular lumen, due either to cell death or to defective cell-to-cell or cell-to-baseme




In patients with ischemic or toxic injury to the tubular epithelial cells, cell sloughing into the tubular lumen, due either to cell death or to defective cell-to-cell or cell-to-basement membrane adhesion, may lead to the formation of granular and/or epithelial cell casts
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e, deeply-pigmented granular casts (ie, "muddy brown" or heme-granular casts) are considered characteristic of ATN, the leading cause of acute kidney injury (AKI) in hospitalized patients [56]. <span>In patients with ischemic or toxic injury to the tubular epithelial cells, cell sloughing into the tubular lumen, due either to cell death or to defective cell-to-cell or cell-to-basement membrane adhesion, may lead to the formation of granular and/or epithelial cell casts. (See "Pathogenesis and etiology of ischemic acute tubular necrosis", section on 'Epithelial cell injury and dysfunction'.) Hyaline casts — Hyaline casts are only slightly more refracti




Whether crystals form in the urine depends upon a variety of factors, including the degree of concentration of constituent molecules, the urine pH, and the presence of inhibitors of crystallization.
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elieved to be due to their formation in large dilated tubules with little flow (picture 12). The presence of broad casts is typically associated with advanced chronic kidney disease. Crystals — <span>Whether crystals form in the urine depends upon a variety of factors, including the degree of concentration of constituent molecules, the urine pH, and the presence of inhibitors of crystallization. Many different forms may be observed in normal patients and in those with defined disorders: ●Uric acid crystals – Uric acid crystals as well as amorphous urates are observed in acid ur




Uric acid crystals as well as amorphous urates are observed in acid urine, a milieu that favors the conversion of the relatively soluble urate salt into the insoluble uric acid (picture 13A-B).
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nt molecules, the urine pH, and the presence of inhibitors of crystallization. Many different forms may be observed in normal patients and in those with defined disorders: ●Uric acid crystals – <span>Uric acid crystals as well as amorphous urates are observed in acid urine, a milieu that favors the conversion of the relatively soluble urate salt into the insoluble uric acid (picture 13A-B). (See "Uric acid renal diseases".) ●Calcium oxalate or calcium phosphate crystals – Calcium oxalate crystals, which are not dependent upon the urine pH, may appear in the monohydrate for




Calcium oxalate crystals, which are not dependent upon the urine pH, may appear in the monohydrate form with a characteristic "dumbbell" appearance or in the dihydrate form as an envelope-like structure. Calcium phosphate crystals only form in a relatively alkaline urine and have a characteristic coffin-like structure (picture 14A-B).
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that favors the conversion of the relatively soluble urate salt into the insoluble uric acid (picture 13A-B). (See "Uric acid renal diseases".) ●Calcium oxalate or calcium phosphate crystals – <span>Calcium oxalate crystals, which are not dependent upon the urine pH, may appear in the monohydrate form with a characteristic "dumbbell" appearance or in the dihydrate form as an envelope-like structure. Calcium phosphate crystals only form in a relatively alkaline urine and have a characteristic coffin-like structure (picture 14A-B). (See "Kidney stones in adults: Epidemiology and risk factors".) ●Cystine crystals – Cystine crystals, with their characteristic hexagonal shape, are diagnostic of cystinuria (picture 15




Cystine crystals, with their characteristic hexagonal shape, are diagnostic of cystinuria (picture 15).
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als only form in a relatively alkaline urine and have a characteristic coffin-like structure (picture 14A-B). (See "Kidney stones in adults: Epidemiology and risk factors".) ●Cystine crystals – <span>Cystine crystals, with their characteristic hexagonal shape, are diagnostic of cystinuria (picture 15). (See "Cystine stones".) ●Magnesium ammonium phosphate crystals – Magnesium ammonium phosphate (struvite) and calcium carbonate-apatite are the constituents of struvite stones (picture 1




Magnesium ammonium phosphate (struvite) and calcium carbonate-apatite are the constituents of struvite stones (picture 16). Normal urine is undersaturated with ammonium phosphate. Struvite stone formation occurs only when ammonia production is increased and the urine pH is elevated, which decreases the solubility of phosphate. Both increased ammonia production and increased urine pH occur only in the setting of a urinary tract infection with a urease-producing organism, such as Proteus or Klebsiella.
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s".) ●Cystine crystals – Cystine crystals, with their characteristic hexagonal shape, are diagnostic of cystinuria (picture 15). (See "Cystine stones".) ●Magnesium ammonium phosphate crystals – <span>Magnesium ammonium phosphate (struvite) and calcium carbonate-apatite are the constituents of struvite stones (picture 16). Normal urine is undersaturated with ammonium phosphate. Struvite stone formation occurs only when ammonia production is increased and the urine pH is elevated, which decreases the solubility of phosphate. Both increased ammonia production and increased urine pH occur only in the setting of a urinary tract infection with a urease-producing organism, such as Proteus or Klebsiella. (See "Pathogenesis and clinical manifestations of struvite stones".) The observation of crystals in the urine is useful in patients with known or suspected kidney stones and is a risk f




The combination of AKI and calcium oxalate crystals, which may suggest ethylene glycol ingestion
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nostic utility in other settings: ●The presence of magnesium ammonium phosphate crystals, which is consistent with infection (see "Pathogenesis and clinical manifestations of struvite stones") ●<span>The combination of AKI and calcium oxalate crystals, which may suggest ethylene glycol ingestion (see "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Clinical features of overdose') ●The presence of a larger number of uric




The observation of crystals in the urine is useful in patients with known or suspected kidney stones and is a risk factor for recurrent calcium oxalate [57] or cystine [58] stone formation
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e pH occur only in the setting of a urinary tract infection with a urease-producing organism, such as Proteus or Klebsiella. (See "Pathogenesis and clinical manifestations of struvite stones".) <span>The observation of crystals in the urine is useful in patients with known or suspected kidney stones and is a risk factor for recurrent calcium oxalate [57] or cystine [58] stone formation. In addition, crystalluria may have diagnostic utility in other settings: ●The presence of magnesium ammonium phosphate crystals, which is consistent with infection (see "Pathogenesis a




The presence of a larger number of uric acid crystals occurring in association with AKI, which may suggest tumor lysis syndrome
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ls, which may suggest ethylene glycol ingestion (see "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Clinical features of overdose') ●<span>The presence of a larger number of uric acid crystals occurring in association with AKI, which may suggest tumor lysis syndrome (see "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors" and "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, e




Lipid droplets, composed primarily of cholesterol esters and, to a lesser degree, cholesterol, are commonly seen on urinalysis in patients with conditions that are associated with the nephrotic syndrome [59,60].
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ce of bacteriuria is generally guided by patient symptoms (picture 17). Fungi are also frequently present (picture 17). (See "Asymptomatic bacteriuria in adults".) THE ASSESSMENT OF LIPIDURIA — <span>Lipid droplets, composed primarily of cholesterol esters and, to a lesser degree, cholesterol, are commonly seen on urinalysis in patients with conditions that are associated with the nephrotic syndrome [59,60]. These fat droplets may be free within sloughed tubular cells (called oval fat bodies) or within casts (called fatty casts) (picture 3D). Fat droplets have a characteristic "Maltese cros




Fat droplets are round and may be confused with red cells. They can be differentiated from red cells under routine light microscopy by their variable size (ranging from larger to much smaller than red cells), their dark outline, and the "Maltese cross" appearance under polarized light
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ughed tubular cells (called oval fat bodies) or within casts (called fatty casts) (picture 3D). Fat droplets have a characteristic "Maltese cross" appearance under polarized light (picture 3E). <span>Fat droplets are round and may be confused with red cells. They can be differentiated from red cells under routine light microscopy by their variable size (ranging from larger to much smaller than red cells), their dark outline, and the "Maltese cross" appearance under polarized light. The origin of urinary lipid is not well understood [60]. The initial step is the filtration of lipoprotein-bound cholesterol, particularly HDL-cholesterol. Filtration of lipoproteins i




The origin of urinary lipid is not well understood [60]. The initial step is the filtration of lipoprotein-bound cholesterol, particularly HDL-cholesterol. Filtration of lipoproteins is minimal in healthy individuals but is markedly enhanced when glomerular permeability to macromolecules is increased in the nephrotic syndrome. Some of the filtered lipoprotein is taken up by the proximal tubular cells.
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d cells under routine light microscopy by their variable size (ranging from larger to much smaller than red cells), their dark outline, and the "Maltese cross" appearance under polarized light. <span>The origin of urinary lipid is not well understood [60]. The initial step is the filtration of lipoprotein-bound cholesterol, particularly HDL-cholesterol. Filtration of lipoproteins is minimal in healthy individuals but is markedly enhanced when glomerular permeability to macromolecules is increased in the nephrotic syndrome. Some of the filtered lipoprotein is taken up by the proximal tubular cells. The cholesterol will be seen in the urine sediment as an oval fat body when the cell is desquamated and/or as free droplets or in fatty casts if the lipid is extruded from the cells. Be




Because of the apparent requirement for increased glomerular permeability, lipiduria is almost always diagnostic of some form of glomerular disease (see "Glomerular disease: Evaluation and differential diagnosis in adults"). One exception is autosomal dominant polycystic kidney disease [61,62]
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lar cells. The cholesterol will be seen in the urine sediment as an oval fat body when the cell is desquamated and/or as free droplets or in fatty casts if the lipid is extruded from the cells. <span>Because of the apparent requirement for increased glomerular permeability, lipiduria is almost always diagnostic of some form of glomerular disease (see "Glomerular disease: Evaluation and differential diagnosis in adults"). One exception is autosomal dominant polycystic kidney disease [61,62]. In one report, urinary oval fat bodies were observed in 21 of 35 patients with autosomal dominant polycystic kidney disease whose average proteinuria on dipstick was only 1+ [61]. Oval




Hematuria with dysmorphic RBCs, RBC casts, and proteinuria — This constellation of findings (eg, dysmorphic red blood cells [RBCs], RBC casts, and proteinuria) is suggestive of a proliferative glomerular disease, which, in the setting of rapidly declining kidney function, constitutes a nephrologic emergency
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y findings must be interpreted in the context of the history, physical exam, and available laboratory data (table 2). Patterns of urinary findings and the diagnoses to which they point include: <span>Hematuria with dysmorphic RBCs, RBC casts, and proteinuria — This constellation of findings (eg, dysmorphic red blood cells [RBCs], RBC casts, and proteinuria) is suggestive of a proliferative glomerular disease, which, in the setting of rapidly declining kidney function, constitutes a nephrologic emergency (picture 3A-E). (See "Glomerular disease: Evaluation and differential diagnosis in adults".) Heavy proteinuria with absent or minimal hematuria — Heavy proteinuria with oval fat bodies,




Heavy proteinuria with oval fat bodies, lipid-laden casts, and absent or minimal hematuria is indicative of nonproliferative glomerular diseases including severe diabetic nephropathy. In addition, this pattern may be seen with membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, and amyloidosis, each of which has both primary and secondary forms
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y function, constitutes a nephrologic emergency (picture 3A-E). (See "Glomerular disease: Evaluation and differential diagnosis in adults".) Heavy proteinuria with absent or minimal hematuria — <span>Heavy proteinuria with oval fat bodies, lipid-laden casts, and absent or minimal hematuria is indicative of nonproliferative glomerular diseases including severe diabetic nephropathy. In addition, this pattern may be seen with membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, and amyloidosis, each of which has both primary and secondary forms. (See "Overview of heavy proteinuria and the nephrotic syndrome".) Granular or epithelial cell casts and renal tubular epithelial cells — In a patient with acute kidney injury (AKI), th




In a patient with acute kidney injury (AKI), the presence of granular and/or epithelial cell casts with or without free renal tubular epithelial cells is strongly suggestive of acute tubular necrosis (ATN) (picture 18A-B). The number of observed granular or renal tubular casts may also have prognostic significance; in a study of patients with ATN who were diagnosed based upon clinical criteria, a semiquantitative assessment of the burden of granular or renal tubular epithelial cell casts on low-powered fields was associated with an increased risk of death or the subsequent need for renal replacement therapy
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sis, each of which has both primary and secondary forms. (See "Overview of heavy proteinuria and the nephrotic syndrome".) Granular or epithelial cell casts and renal tubular epithelial cells — <span>In a patient with acute kidney injury (AKI), the presence of granular and/or epithelial cell casts with or without free renal tubular epithelial cells is strongly suggestive of acute tubular necrosis (ATN) (picture 18A-B). The number of observed granular or renal tubular casts may also have prognostic significance; in a study of patients with ATN who were diagnosed based upon clinical criteria, a semiquantitative assessment of the burden of granular or renal tubular epithelial cell casts on low-powered fields was associated with an increased risk of death or the subsequent need for renal replacement therapy [63]. The presence and quantity of granular casts or renal tubular epithelial cells in the urine was evaluated as a diagnostic tool in 267 patients with hospitalized AKI [64]. Prior to




The presence and quantity of granular casts or renal tubular epithelial cells in the urine was evaluated as a diagnostic tool in 267 patients with hospitalized AKI [64]. Prior to performing a urinalysis, trained clinicians were asked to make a clinical diagnosis of ATN, prerenal AKI, or other. Since kidney biopsies were not routinely performed, the final diagnosis of ATN versus prerenal disease was determined by whether the renal function improved within 48 hours after fluid resuscitation and/or hemodynamic manipulation. The following observations were made:

● A pre-urinalysis diagnosis (based upon the history, physical examination, and other available data) of ATN had a positive predictive value of 86 percent. In such patients who also had at least one granular cast or tubular epithelial cell in the urinalysis, the positive predictive value increased to 100 percent. Of patients with a pre-urinalysis diagnosis of ATN and no granular casts or tubular epithelial cells, 44 percent had a final diagnosis of ATN. Thus, a diagnosis of ATN is still possible even if the urinalysis has no granular casts or tubular epithelial cells.

● A pre-urinalysis diagnosis of prerenal AKI had a positive predictive value of 77 percent. In such patients, the absence of granular casts or tubular epithelial cells increased the positive predictive value to 91 percent for a final diagnosis of prerenal AKI

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of the burden of granular or renal tubular epithelial cell casts on low-powered fields was associated with an increased risk of death or the subsequent need for renal replacement therapy [63]. <span>The presence and quantity of granular casts or renal tubular epithelial cells in the urine was evaluated as a diagnostic tool in 267 patients with hospitalized AKI [64]. Prior to performing a urinalysis, trained clinicians were asked to make a clinical diagnosis of ATN, prerenal AKI, or other. Since kidney biopsies were not routinely performed, the final diagnosis of ATN versus prerenal disease was determined by whether the renal function improved within 48 hours after fluid resuscitation and/or hemodynamic manipulation. The following observations were made: ●A pre-urinalysis diagnosis (based upon the history, physical examination, and other available data) of ATN had a positive predictive value of 86 percent. In such patients who also had at least one granular cast or tubular epithelial cell in the urinalysis, the positive predictive value increased to 100 percent. Of patients with a pre-urinalysis diagnosis of ATN and no granular casts or tubular epithelial cells, 44 percent had a final diagnosis of ATN. Thus, a diagnosis of ATN is still possible even if the urinalysis has no granular casts or tubular epithelial cells. ●A pre-urinalysis diagnosis of prerenal AKI had a positive predictive value of 77 percent. In such patients, the absence of granular casts or tubular epithelial cells increased the positive predictive value to 91 percent for a final diagnosis of prerenal AKI. The presence of granular casts and tubular epithelial cells in the urine was also associated with progression of AKI in the hospital [65]. Patients whose urinalyses revealed six or mor




Isolated pyuria is usually indicative of bacterial urinary tract infection. The differential diagnosis is broad if a concurrent urine culture is negative and includes a partially or recently treated urinary tract infection, non-bacterial infections (including tuberculosis), prostatitis, interstitial nephritis, and nephrolithiasis [50]
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veloping worse kidney function, initiation of dialysis, or death compared with patients who had no granular casts or tubular epithelial cells (54-67 percent versus 9 percent). Isolated pyuria — <span>Isolated pyuria is usually indicative of bacterial urinary tract infection. The differential diagnosis is broad if a concurrent urine culture is negative and includes a partially or recently treated urinary tract infection, non-bacterial infections (including tuberculosis), prostatitis, interstitial nephritis, and nephrolithiasis [50]. Normal or near-normal urinalysis — In patients with AKI, a relatively normal urinalysis (few cells with little or no proteinuria and no casts other than hyaline casts) can be associate




In patients with AKI, a relatively normal urinalysis (few cells with little or no proteinuria and no casts other than hyaline casts) can be associated with ATN but may also indicate one of the following diseases:

● Prerenal AKI due to either an actual or effective decrease in circulating volume

● Urinary tract obstruction

● Hypercalcemia

● Cast nephropathy in multiple myeloma

● Vascular disease that produces glomerular ischemia but not infarction (eg, hypertensive emergency, scleroderma, thrombotic microangiopathies) or that affects extra-glomerular vessels (eg, cholesterol atheroemboli, polyarteritis nodosa)

● Tumor lysis syndrome

● Acute phosphate nephropathy

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or recently treated urinary tract infection, non-bacterial infections (including tuberculosis), prostatitis, interstitial nephritis, and nephrolithiasis [50]. Normal or near-normal urinalysis — <span>In patients with AKI, a relatively normal urinalysis (few cells with little or no proteinuria and no casts other than hyaline casts) can be associated with ATN but may also indicate one of the following diseases: ●Prerenal AKI due to either an actual or effective decrease in circulating volume ●Urinary tract obstruction ●Hypercalcemia ●Cast nephropathy in multiple myeloma ●Vascular disease that produces glomerular ischemia but not infarction (eg, hypertensive emergency, scleroderma, thrombotic microangiopathies) or that affects extra-glomerular vessels (eg, cholesterol atheroemboli, polyarteritis nodosa) ●Tumor lysis syndrome ●Acute phosphate nephropathy In patients with chronic kidney disease, a normal urinalysis most commonly indicates states of persistently decreased effective circulating volume, such as in patients with heart failur




In patients with chronic kidney disease, a normal urinalysis most commonly indicates states of persistently decreased effective circulating volume, such as in patients with heart failure, urinary tract obstruction, chronic tubulointerstitial diseases, light chain cast nephropathy, and ischemic or hypertensive nephrosclerosis.
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ency, scleroderma, thrombotic microangiopathies) or that affects extra-glomerular vessels (eg, cholesterol atheroemboli, polyarteritis nodosa) ●Tumor lysis syndrome ●Acute phosphate nephropathy <span>In patients with chronic kidney disease, a normal urinalysis most commonly indicates states of persistently decreased effective circulating volume, such as in patients with heart failure, urinary tract obstruction, chronic tubulointerstitial diseases, light chain cast nephropathy, and ischemic or hypertensive nephrosclerosis. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain langu