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Specific gravity Urinary pH Determination of urinary pH is useful in the diagnosis and management of UTIs and calculi. Alkaline urine in a patient with a UTI suggests the presence of a urea-splitting organism, which may be associated with magnesium-ammonium phosphate crystals and can form staghorn calculi. Uric acid calculi are associated with acidic urine Hematuria |
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TABLE 4 Common Causes of Hematuria |
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Glomerular causes Familial causes Fabry's disease Hereditary nephritis (Alport's syndrome) Nail-patella syndrome Thin basement-membrane disease Primary glomerulonephritis Focal segmental glomerulonephritis Goodpasture's disease Henoch-Schönlein purpura IgA nephropathy (Berger's disease) Mesangioproliferative glomerulonephritis Postinfectious glomerulonephritis Rapidly progressive glomerulonephritis Secondary glomerulonephritis Hemolytic-uremic syndrome Systemic lupus nephritis Thrombotic thrombocytopenic purpura Vasculitis |
Renal causes Arteriovenous malformation Hypercalciuria Hyperuricosuria Loin pain-hematuria syndrome Malignant hypertension Medullary sponge kidney Metabolic causes Papillary necrosis Polycystic kidney disease Renal artery embolism Renal vein thrombosis Sickle cell disease or trait Tubulointerstitial causes Vascular cause |
Urologic causes Benign prostatic hyperplasia Cancer (kidney, ureteral, bladder, prostate, and urethral) Cystitis/pyelonephritis Nephrolithiasis Prostatitis Schistosoma haematobium infection Tuberculosis Other causes Drugs (e.g., NSAIDs, heparin, warfarin [Coumadin], cyclophosphamide [Cytoxan]) Trauma (e.g., contact sports, running, Foley catheter) |
| NSAIDs = nonsteroidal anti-inflammatory drugs. Adapted with permission from Ahmed Z, Lee J. Asymptomatic urinary abnormalities. Hematuria and proteinuria. Med Clin North Am 1997;81:644. |
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Glomerular Hematuria. Glomerular hematuria typically is associated with significant proteinuria, erythrocyte casts, and dysmorphic RBCs. However, 20 percent of patients with biopsy-proven glomerulonephritis present with hematuria alone.22 IgA nephropathy (i.e., Berger's disease) is the most common cause of glomerular hematuria. Renal (Nonglomerular) Hematuria. Nonglomerular hematuria is secondary to tubulointerstitial, renovascular, or metabolic disorders. Like glomerular hematuria, it often is associated with significant proteinuria; however, there are no associated dysmorphic RBCs or erythrocyte casts. Further evaluation of patients with glomerular and nonglomerular hematuria should include determination of renal function and 24-hour urinary protein or spot urinary protein-creatinine ratio. Urologic Hematuria. Urologic causes of hematuria include tumors, calculi, and infections. Urologic hematuria is distinguished from other etiologies by the absence of proteinuria, dysmorphic RBCs, and erythrocyte casts. Even significant hematuria will not elevate the protein concentration to the 2+ to 3+ range on the dipstick test.23 Up to 20 percent of patients with gross hematuria have urinary tract malignancy; a full work-up with cystoscopy and upper-tract imaging is indicated in patients with this condition.24 In patients with asymptomatic microscopic hematuria (without proteinuria or pyuria), 5 to 22 percent have serious urologic disease, and 0.5 to 5 percent have a genitourinary malignancy.25-29 Exercise-induced hematuria is a relatively common, benign condition that often is associated with long-distance running. Results of repeat urinalysis after 48 to 72 hours should be negative in patients with this condition.30 Proteinuria In healthy persons, the glomerular capillary wall is permeable only to substances with a molecular weight of less than 20,000 Daltons. Once filtered, low-molecular-weight proteins are reabsorbed and metabolized by the proximal tubule cells. Normal urinary proteins include albumin, serum globulins, and proteins secreted by the nephron. Proteinuria is defined as urinary protein excretion of more than 150 mg per day (10 to 20 mg per dL) and is the hallmark of renal disease. Microalbuminuria is defined as the excretion of 30 to 150 mg of protein per day and is a sign of early renal disease, particularly in diabetic patients. The reagent on most dipstick tests is sensitive to albumin but may not detect low concentrations of γ-globulins and Bence Jones proteins. Dipstick tests for trace amounts of protein yield positive results at concentrations of 5 to 10 mg per dL-lower than the threshold for clinically significant proteinuria.15 A result of 1+ corresponds to approximately 30 mg of protein per dL and is considered positive; 2+ corresponds to 100 mg per dL, 3+ to 300 mg per dL, and 4+ to 1,000 mg per dL.31,32 Dipstick urinalysis reliably can predict albuminuria with sensitivities and specificities of greater than 99 percent.4 Asymptomatic proteinuria is associated with significant renal disease in less than 1.5 percent of patients.4,33 Proteinuria can be classified as transient or persistent (Table 5).21 In transient proteinuria, a temporary change in glomerular hemodynamics causes the protein excess; these conditions follow a benign, self-limited course.34,35 Orthostatic (postural) proteinuria is a benign condition that can result from prolonged standing; it is confirmed by obtaining a negative urinalysis result after eight hours of recumbency. |
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TABLE 5 Common Causes of Proteinuria |
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Transient proteinuria Congestive heart failure Dehydration Emotional stress Exercise Fever Orthostatic (postural) proteinuria Seizures Persistent proteinuria Primary glomerular causes Focal segmental glomerulonephritis IgA nephropathy (i.e., Berger's disease) IgM nephropathy Membranoproliferative glomerulonephritis Membranous nephropathy Minimal change disease |
Secondary glomerular causes Alport's syndrome Amyloidosis Collagen vascular diseases Diabetes mellitus Drugs (e.g., NSAIDs, penicillamine [Cuprimine], gold, ACE inhibitors) Fabry's disease Infections (e.g., HIV, syphilis, hepatitis, Malignancies (e.g., lymphoma, solid Sarcoidosis Sickle cell disease |
Tubular causes Aminoaciduria Drugs (e.g., NSAIDs, antibiotics) Fanconi syndrome Heavy metal ingestion Hypertensive nephrosclerosis Interstitial nephritis Overflow causes Hemoglobinuria Multiple myeloma Myoglobinuria |
| NSAIDs = nonsteroidal anti-inflammatory drugs; ACE = angiotensin-converting enzyme; HIV = human immunodeficiency virus. Adapted with permission from Ahmed Z, Lee J. Asymptomatic urinary abnormalities. Hematuria and proteinuria. Med Clin North Am 1997;81:650. |
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Persistent proteinuria is divided into three general categories:glomerular, tubular, and overflow. In glomerular proteinuria, the most common type, albumin is the primary urinary protein. Tubular proteinuria results when malfunctioning tubule cells no longer metabolize or reabsorb normally filtered protein. In this condition, low-molecular-weight proteins predominate over albumin and rarely exceed 2 g per day. In overflow proteinuria, low-molecular-weight proteins overwhelm the ability of the tubules to reabsorb filtered proteins. Further evaluation of persistent proteinuria usually includes determination of 24-hour urinary protein excretion or spot urinary protein-creatinine ratio, microscopic examination of the urinary sediment, urinary protein electrophoresis, and assessment of renal function.32 Glycosuria Glucose normally is filtered by the glomerulus, but it is almost completely reabsorbed in the proximal tubule. Glycosuria occurs when the filtered load of glucose exceeds the ability of the tubule to reabsorb it (i.e., 180 to 200 mg per dL). Etiologies include diabetes mellitus, Cushing's syndrome, liver and pancreatic disease, and Fanconi's syndrome. Ketonuria Ketones, products of body fat metabolism, normally are not found in urine. Dipstick reagents detect acetic acid through a reaction with sodium nitroprusside or nitroferricyanide and glycine. Ketonuria most commonly is associated with uncontrolled diabetes, but it also can occur during pregnancy, carbohydrate-free diets, and starvation. Nitrites Nitrites normally are not found in urine but result when bacteria reduce urinary nitrates to nitrites. Many gram-negative and some gram-positive organisms are capable of this conversion, and a positive dipstick nitrite test indicates that these organisms are present in significant numbers (i.e., more than 10,000 per mL). This test is specific but not highly sensitive. Thus, a positive result is helpful, but a negative result does not rule out UTI.6 The nitrite dipstick reagent is sensitive to air exposure, so containers should be closed immediately after removing a strip. After one week of exposure, one third of strips give false-positive results, and after two weeks, three fourths give false-positive results.36 Non-nitrate-reducing organisms also may cause false-negative results, and patients who consume a low-nitrate diet may have false-negative results. Leukocyte esterase Leukocyte esterase is produced by neutrophils and may signal pyuria associated with UTI. To detect significant pyuria accurately, five minutes should be allowed for the dipstick reagent strip to change color. Leukocyte casts in the urinary sediment can help localize the area of inflammation to the kidney. Organisms such as Chlamydia and Ureaplasma urealyticum should be considered in patients with pyuria and negative cultures. Other causes of sterile pyuria include balanitis, urethritis, tuberculosis, bladder tumors, viral infections, nephrolithiasis, foreign bodies, exercise, glomerulonephritis, and corticosteroid and cyclophosphamide (Cytoxan) use. Bilirubin and urobilinogen Urine normally does not contain detectable amounts of bilirubin. Unconjugated bilirubin is water insoluble and cannot pass through the glomerulus; conjugated bilirubin is water soluble and indicates further evaluation for liver dysfunction and biliary obstruction when it is detected in the urine. Normal urine contains only small amounts of urobilinogen, the end product of conjugated bilirubin after it has passed through the bile ducts and been metabolized in the intestine. Urobilinogen is reabsorbed into the portal circulation, and a small amount eventually is filtered by the glomerulus. Hemolysis and hepatocellular disease can elevate urobilinogen levels, and antibiotic use and bile duct obstruction can decrease urobilinogen levels. Microscopic Urinalysis Microscopic examination is an indispensable part of urinalysis; the identification of casts, cells, crystals, and bacteria aids in the diagnosis of a variety of conditions. To prepare a urine specimen for microscopic analysis, a fresh sample of 10 to 15 mL of urine should be centrifuged at 1,500 to 3,000 rpm for five minutes. The supernatant then is decanted and the sediment resuspended in the remaining liquid.37 A single drop is transferred to a clean glass slide, and a cover slip is applied. |
 Figure 1. Squamous epithelial cells (arrows) and leukocytes (200 X). |
 Figure 2. Convoluted renal tubule cells (200 X). |
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