SOURCE: Woo K, Lau YK. Singapore Med J. 2001;42(8):385–389.
Summary of Key Points in Proteinuria
• Urine dipstick test is most sensitive to albumin and less sensitive to low-molecular-weight proteins.
• False-positive results may occur in highly alkaline urine.
• Quantitative methods such as 24-hour urine protein collection, protein-to-creatinine ratio or albumin to-creatinine ratio should be considered for further evaluation of proteinuria.
• Random spot urine protein-to-creatinine ratio (PCR) accurately estimates 24-hour total protein measurement. Sulfosalicylic acid (SSA) can be used for dipstick-negative proteinuria to detect positively charged light chains of immunoglobulins.
• Proteinuria is defined as >150 mg/day of urinary protein.
• Presence of proteinuria indicates renal injury (table 65.4).
• In orthostatic proteinuria, suspected cases should be confirmed by an 8-hour overnight urinary measurement demonstrating <50 mg/day.
BLOOD
The dipstick test is dependent on the pseudoperoxidase activity of hemoglobin. The dipstick test has a sensitivity range of approximately 91–100% with specificity ranging from 65% to 99%. It is more sensitive to free hemoglobin and myoglobin than to intact erythrocytes. Hemoglobin detected on dipstick may occur as a result of hematuria, intravascular hemolysis, or myoglobinuria that can be secondary to conditions such as rhabdomyolysis. A positive result may also occur with lysis of erythrocytes on standing, an alkaline pH, or a low relative density (especially <1.010). When the dipstick test for hemoglobin is positive, microscopic sediment examination should be performed to distinguish hematuria from other causes.
Hematuria is defined by three or more red blood cells per high-powered field. The presence of hematuria is always an abnormal finding and may result from renal or extrarenal causes (Figure 65.1). The most benign form of hematuria is its appearance after vigorous exercise (in marathon runners), which disappears in 24–48 hours.
Figure 65.1. Common differential diagnoses for hematuria.
Summary of Key Points on Positive Dipstick for Blood
• Dipstick test is dependent on the pseudoperoxidase activity of hemoglobin.
• Dipstick test is more sensitive to free hemoglobin and myoglobin than to intact erythrocytes.
• It has sensitivity of 91–100% and specificity of 65–99%.
• Microscopic sediment examination should be performed in positive cases.
• Positive dipstick test may occur in hematuria, intravascular hemolysis, or myoglobinuria such as in rhabdomyolysis.
• Hematuria is defined as three or more red blood cells per high-powered field and is indicative of renal or extrarenal pathologies.
LEUKOCYTES
The urine dipstick detects leukocyte esterase released from lysed neutrophils and is indicative of pyuria associated with glomerular and/or interstitial inflammation or lower urinary tract infection. The dipstick reagent strip should be allowed to stand for 1 minute before reading to detect significant pyuria accurately. False-positive results can occur with granulocyte lysis in longstanding urine or glomerular epithelial cells that can contaminate the specimen. False-negative results may occur with hyperglycemia, albuminuria, tetracycline, cephalosporins, and oxaluria.
Bacteria produce nitrites by the reduction of urinary nitrates that can be detected by urine dipstick. This process occurs in the presence of many gram-negative and some gram-positive organisms. False-negative results can occur in the presence of ascorbic acid and high specific gravity. They may also occur with low levels of urinary nitrate due to diet, prolonged storage of urine, and rapid transit of urine in the bladder. Urinary tract infection is more likely if both leukocyte esterase and nitrites are positive on dipstick examination. However, infection cannot be definitively ruled out if both tests are negative.
MICROSCOPIC EXAMINATION
Microscopic examination of the urine sediment is necessary for a complete urinalysis. The identification of cells, casts, crystals, lipids, and organisms can yield important diagnostic information. Examination of urinary sediment provides clues to diagnosis and management of renal or urinary tract disease and to detection of metabolic or systemic disease not directly related to the kidney.
CELLS
Erythrocytes, leukocytes, and epithelial cells are the three main types of cells found in urine in various pathologic conditions (see table 65.5; figures 65.2–65.4).
Table 65.5 MICROSCOPIC EXAMINATION OF CELLS IN URINE
SOURCES: Birch et al. Clin Nephrol. 1983;20(2):78–84; Pollock et al. Kidney Int. 1989;36(6):1045–1049; Pollock Am J Med. 1983;75(1B):79–84; Fogazzi et al. J Nephrol. 2005;18(6):703–710; Nolan and Kelleher et al. N Engl J Med. 1986;315(24):1516–1519; Nolan. Clin Lab Med. 1988;8(3):555–565;Tetu. Mod Pathol. 2009;22 (Suppl 2):S53–S59; Skoberne et al. Am J Physiol Renal Physiol. 2009;296(2):F230–F241.
Figure 65.2. Erythrocytes in Urinary Sediments. (A) Isomorphic red blood cells which are uniformly round, biconcave, 7 µm in diameter, and have ample hemoglobin. These increased numbers are typically associated with lower urinary tract inflammation. ×400 magnification. (B) Dysmorphic RBC in urine sediment in glomerular hematuria. ×4000. (C) Erythrocytes under phase contrast—oil droplets.
Figure 65.3. Leukocytes in Urinary Sediments. Polymorphonuclear leukocytes in which the lobed nuclei are readily evident (A, arrow and B). These increased numbers may be associated with lower urinary tract infection or with renal disease affecting either tubules, interstitium, or the glomerulus. ×400 magnification.
Figure 65.4. Epithelial Cells in Urinary Sediments. (A) Squamous epithelial cells. (B) Transitional epithelial cells in the presence of bacteria (arrow).
CASTS
The formation of casts occur when proteins, predominantly Tamm-Horsfall protein secreted by cells of the thick ascending limb of the loop of Henle trap cells, fat, bacteria, and other inclusions. These amalgamations are then excreted in urine (table 65.6; figures 65.5–65.7).
Table 65.6 MICROSCOPIC EXAMINATION OF CASTS IN URINE
| PATHOLOGIC CAUSES AND DESCRIPTION | |
| Hyaline (Figure 65.5A) | Can be observed under normal conditions, in concentrated acidic urine and under various physiological states, including strenuous exercise, dehydration, and febrile disease. |
| Large numbers are frequently seen in congestive heart failure and minimal change disease nephrotic syndrome. | |
| Granular (Figure 65.5B and 65.5C) | Formed from amalgamation of Tamm-Horsfall protein, debris of cells, and plasma proteins. |
| Classification as finely or coarsely granular casts depends on how much digestion of debris has occurred within cast. | |
| Nonspecific causes and can be observed in a variety of glomerular or tubular diseases. | |
| In acute tubular necrosis, large numbers of “muddy brown” granular casts can be observed. | |
| Waxy (Figure 65.6A and 65.6B) | Opaque, formed from degeneration of hyaline, granular, and cellular casts. |
| Can be detected by light microscopy. | |
| Observed in CKD and have been reported as frequent finding in rapidly progressive glomerulonephritis. | |
| Fatty (Figure 65.6C) | Formed by lipid droplets. |
| Frequently are doubly refractile (Maltese crosses). | |
| Seen in nephrotic syndrome and mercury poisoning. | |
| Red cell (Figure 65.7A) | Active glomerular injury and is a finding that signifies serious glomerular disease. |
| Characteristic of proliferative extra- and endocapillary necrotizing glomerulonephritis. | |
| Leukocyte (Figure 65.7B) | Reflects trapping of WBCs within a matrix of tubular proteins (must distinguish from WBCs appearing in clusters, which have no distinct borders). |
| Observed in acute pyelonephritis, acute interstitial nephritis and other interstitial inflammatory processes. | |
| More frequent observation in glomerulonephritis than RBC casts and reflect the degree of inflammation. | |
| Renal tubular epithelial (RTE) cell casts (Figure 65.7C) | Typically observed in acute tubular necrosis, acute interstitial nephritis, and also less frequently in glomerular disorders. |
SOURCE: Serafini-Cessi F, Malagolini N, Cavallone D. Am J Kidney Dis, 2003;42(4):658–676. | |
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