INTRODUCTION

Kidney disease, whether acute or chronic, may present with systemic features of renal injury (hypertension, edema, uremia), renal limited manifestations (flank or loin pain, gross hematuria), or asymptomatically with only abnormalities in blood testing or urinalysis. Kidney disease is fully assessed with complete history and physical examination, directed blood testing, and examination of the urinary sediment. Although the urinary sediment evaluation does not measure level of renal function, it is extremely important in providing insight into the cause of kidney disease and may also provide prognostic information in the setting of prerenal acute kidney injury (AKI) and acute tubular necrosis (ATN). Thus, in addition to urinalysis, the clinical examination, estimates of glomerular filtration rate (GFR), radiologic testing, and renal biopsy are used in combination to assess the patient with kidney disease. This chapter reviews the components of the urinalysis/urine microscopy, as well as their interpretation in patients with kidney disease.

URINALYSIS/URINE MICROSCOPY: ROLE IN KIDNEY DISEASE

Examination of urine in patients with kidney disease provides invaluable information. It is one of the major noninvasive diagnostic tools available to the clinician. The urinalysis is comprised of several components. These include the appearance of the urine, various parameters measured on dipstick and spot collections, and examination of the urine under the microscope. As will be discussed later, urine microscopy is essential to complete the urinalysis and assess kidney disease. The full urinalysis can provide insight into the cause of kidney injury/disease, some of the functional consequences of renal injury, and the course of kidney disease following various interventions. For example, in a patient suffering from acute glomerulonephritis, the urine sediment can provide information about activity of the inflammatory process. It will not always predict eventual renal outcomes, although data support its utility in prognosis in prerenal AKI and ATN. Thus, normalization of the urine sediment may represent either resolution with full recovery of kidney function or healing of the inflammatory process with residual glomerulosclerosis and nephron loss (chronic kidney disease). In this circumstance, other testing is required to accurately predict the status of kidney disease.

Despite some of the limitations of urinalysis, it should be performed in all patients with kidney disease or suspected kidney problems. The urine specimen is examined within an hour of voiding to provide optimal information and eliminate false-positive or false-negative results. A midstream specimen is adequate in men. In women, the external genitalia should be cleaned prior to voiding to avoid contamination of the urine with vaginal secretions. Following collection, dipstick testing is performed and the sample centrifuged at 3000 rpm for 3 to 5 minutes. Urine color and appearance is noted both before and after centrifugation, as this will provide clues to potential causes of the underlying kidney process. The dipstick measures pH, specific gravity, protein (albumin), heme, glucose, leukocyte esterase, bile, and nitrite. The centrifuged specimen is decanted to remove the supernatant and placed in a separate tube. This allows examination of the sediment. A small amount of sediment is placed on a glass slide. A cover slip is applied and both stained and unstained sediment are examined at various powers (100×, 160×, and 400×) under the microscope. These aspects of urinalysis are discussed in more detail throughout the chapter.

KEY POINTS

URINALYSIS: COMPONENTS

Appearance

Initial examination of urine consists of assessment of urine color and appearance. Normal urine is typically clear and light yellow in color. It tends to be lighter when more dilute (large water intake or polyuric states) and darker when more concentrated (overnight water restriction, prerenal disease states). The urine may appear cloudy because of infection (white cells, bacteria, proteinaceous material) or crystalluria (uric acid or calcium-containing crystals). The urine can look white from the presence of pyuria or calcium phosphate crystals; green from drugs such as methylene blue, amitriptyline, or propofol; or black as a consequence of certain malignancies or ochronosis. Table 14.1 lists some of the substances that can alter urine color. Although these urinary colors are unusual, various shades of red or brown are more common. Intermittent excretion of red to brown urine occurs in a variety of clinical settings. Assessment of red/brown urine should proceed through the following steps:

1. Centrifuge the urine and examine the sediment and supernatant.

2. Red/brown sediment supports hematuria or ATN with muddy brown casts.

3. Red/brown supernatant should be examined further with dipstick testing for the presence of heme.

4. Heme-negative supernatant may be caused by beeturia (beet ingestion in certain hosts), porphyria, or therapy with phenazopyridine (bladder analgesic).

5. Heme-positive supernatant may result from either hemoglobinuria or myoglobinuria. These are distinguished by examination of the plasma that will be red with hemoglobinuria and clear with myoglobinuria.

Dipstick Examination of Urine

Urine dipstick allows rapid examination of the urine for several abnormalities. They include specific gravity, pH, protein, blood/heme, glucose, leukocyte esterase, nitrite, and bile. Each of these components of the dipstick, as well as their application to the evaluation of kidney disease are discussed.

Specific Gravity

The kidney can vary urine osmolality (concentration) to appropriately maintain plasma osmolality within a very narrow range. Thus, the concentration of urine varies markedly based on the status of the patient’s intravascular volume. To assess whether the kidney’s response is appropriate or abnormal for the patient’s volume status, measures of urine concentration are employed. Specific gravity is one such available test. Importantly, the specific gravity and other measures of urine concentration are assessed in correlation with the patient’s clinical state. The specific gravity is defined as the weight of a solution compared with that of an equal volume of water. As such, it is a reasonable reflection of urine concentration. It is most useful in the diagnosis of patients with disorders of water homeostasis (hyponatremia, hypernatremia) and states of polyuria. It can vary significantly, however, with measured urine osmolality under certain clinical situations. For example, the presence of large molecules in the urine such as glucose and radiocontrast media can produce large changes in specific gravity, while having minimal effects on osmolality. These potential confounders must be accounted for when interpreting the specific gravity.

Urinary pH

Urine pH reflects the degree of acidification of urine; hence it is a measure of the urine hydrogen ion concentration. Urine pH normally ranges from 4.5 to 8.0 based on the prevailing systemic acid–base balance. Examination of urine pH is most useful in the workup of a metabolic acidosis. The appropriate response to metabolic acidosis is an increase in renal acid (buffered hydrogen ion) excretion, with a reduction in urine pH to below 5. Urine pH above 5 in the setting of metabolic acidosis may signal kidney disease, such as one of the forms of renal tubular acidosis (RTA). Changes in urine pH to various provocative tests can help distinguish which type of RTA exists. A urine pH less than 5.5 can also suggest risk for crystal and stone formation from uric acid, as well as medications such as sulfadiazine and methotrexate. Alkaline pH (>7.0) can provide clues to various clinical disorders such as urinary infection with urease-producing organisms (Proteus mirabilis) and risk for crystal and stone formation from calcium phosphate and certain drugs (atazanavir, indinavir). Management of these clinical disorders is assessed by measuring urine pH following the appropriate intervention.

Urine Protein

The urine dipstick measures primarily albumin. It does not identify other proteins that may be found in the urine, such as immunoglobulins and their light chains, or proteins secreted by tubular cells. Although the dipstick test is highly specific for the identification of albumin, it is insensitive in the detection of urinary albumin levels that are less than 300 to 500 mg/day. This is an important point as this makes the dipstick an unreliable test in the detection of microalbuminuria in certain patient populations. For example, microalbuminuria is an important early manifestation of diabetic nephropathy, one that would prompt changes in disease management in this population. Waiting for dipstick positive proteinuria allows significant amounts of structural damage to occur prior to aggressively managing kidney disease. Similarly, microalbuminuria is associated with cardiovascular disease in nondiabetic patients and its detection would likely alter management in these patients. In addition to the insensitivity of the dipstick protein measurement, the semiquantitative values (trace, 1+, 2+, 3+, 4+) obtained are only rough guides to actual amounts of proteinuria. Furthermore, these values should be interpreted cautiously recognizing that urine concentration, pH, and substances such as iodinated radiocontrast can influence the dipstick reading. For example, dilute urine can underestimate the degree of proteinuria, whereas both concentrated urine and alkaline urine can overestimate proteinuria. Finally, radiocontrast can cause a false-positive dipstick reading for proteinuria. Therefore, the urine should not be tested for at least 24 hours following radiocontrast administration. Other tests to measure proteinuria are discussed later.

Urine Blood/Heme

Dipstick testing of urine for blood/heme is sensitive in detecting both red blood cells and heme pigment (hemoglobin or myoglobin) in urine. As few as 1 to 2 red blood cells per high-power field register positive on dipstick, making this test at least as sensitive as urine sediment examination. False-positive results (heme pigments) for hematuria can, however, occur. In contrast, false-negative tests are unusual and a dipstick negative for heme reliably excludes hematuria. Importantly, the dipstick test for heme is never a substitute for a thorough urine sediment examination. All patients with hematuria on dipstick should have their urine spun down and the sediment examined closely for any abnormalities, especially evidence of glomerular disease (dysmorphic red blood cells, red blood cell casts) or nephrolithiasis (monomorphic red blood cells, crystals).

Urine Glucose

Dipstick testing for glucose is a relatively insensitive measure of hyperglycemia and is not recommended for screening of patients for diabetes mellitus. Significant glycosuria does not occur until the mean plasma glucose concentration is approximately 180 mg/dL. Additionally, it depends on urine volume. Also, glucose detected semiquantitatively on urine dipstick may reflect a kidney abnormality rather than hyperglycemia. Certain disease states may alter the ability of the kidney to reabsorb filtered glucose in the proximal tubule despite normal plasma glucose concentration. This renal glycosuria can manifest as an isolated proximal tubular defect. More commonly, it can develop in association with other defects in proximal tubular reabsorption including hypophosphatemia (phosphaturia), hypouricemia (uricosuria), RTA (bicarbonaturia), and aminoaciduria. This constellation of proximal tubular dysfunction is termed Fanconi syndrome. This syndrome is hereditary or acquired through diseases (multiple myeloma) or drugs (proximal tubular toxins) that primarily injure proximal tubular cells in kidney. Drugs such as cidofovir, tenofovir, cisplatin, and ifosfamide cause Fanconi syndrome.

Urine Leukocyte Esterase

Positive dipstick testing for leukocyte esterase (LE) represents the presence of white blood cells in urine (pyuria). The test is positive with 2 to 3 leukocytes/high-powered field. A positive test in the absence of white blood cells on urine microscopy suggests that the cells lysed prior to viewing. Importantly, lymphocytes do not produce LE and the dipstick will be LE negative when they are present in the urine. Although the presence of urinary white blood cells most often reflects infection of the urinary tract, it can also be indicative of diseases associated with sterile pyuria. Included are tubulointerstitial nephritis from various causes, crystalluria and nephrolithiasis, and renal mycobacterial infection. As with hematuria, a thorough examination of the urine sediment should be performed in patients with pyuria.

Urine Nitrite

The urine nitrite test is most valuable when used in conjunction with LE to assess a patient for the presence of urinary tract infection. Certain bacteria (Enterobacteriaceae) convert urinary nitrate to nitrite (Figure 14.1). Thus, the combination of LE and nitrite positive tests on dipstick strongly suggests infection with this family of bacteria. Bacteria that do not produce nitrate reductase will not convert nitrate to nitrite and therefore will test negative for nitrite despite urinary tract infection.

Urine Bile

Bile present on urine dipstick reflects the filtration of serum bilirubin. Figure 14.2 illustrates normal bile pigment metabolism. The finding of bile pigment is common in patients with various forms of liver disease with associated hyperbilirubinemia. It does not represent a disturbance in kidney function although liver disease may be associated with renal failure (hepatorenal syndrome). Testing for urine bilirubin and urobilinogen separates obstructive jaundice from other forms of liver disease. In this situation, complete biliary obstruction has positive urine bilirubin with negative urobilinogen, while other forms of liver disease are positive for both substances (Table 14.2).

KEY POINTS

URINE SEDIMENT EXAMINATION

Microscopy of the urine sediment is a very important aspect of the evaluation of patients with known or suspected kidney disease. Urinary sediment should be reported both qualitatively (types of cells, casts, crystals, organisms) and quantitatively (number of casts per low-powered field and cells/crystals per high-powered field). At least 10 and up to 20 microscopic fields should be viewed and an average range reported. For example, 5 to 10 granular casts per low-powered field or 1 to 5 red blood cells per high-powered field. It is important to also recognize that normal subjects without kidney disease may also have minor amounts of abnormal elements (red blood cells, white blood cells, casts, and crystals) in the urine. A patient without kidney disease may have zero to 4 white blood cells or zero to 2 red blood cells in 1 high-powered field and 1 cast, often hyaline in 10 to 20 low-powered fields. Additionally, a few crystals made up of uric acid, calcium oxalate, or calcium phosphate may occasionally be observed. A greater number of these elements in the urine is, however, very suggestive of either systemic or renal-related disease states. Various elements found in urine on sediment examination are described below.

Cellular Elements

The most common cell types observed in urine are red blood cells, white blood cells, and epithelial cells. The urine can also contain cells from the bladder, and when contaminated during collection, vaginal squamous cells can be noted. Less commonly, tumor cells from the uroepithelium (bladder and ureteral epithelium), lymphoma, or leukemic cells that have infiltrated the renal parenchyma, and “decoy cells” associated with BK-polyomavirus–induced changes in renal tubular cells or uroepithelial cells are identified in urine sediment. The various cellular elements present in urine are reviewed below.

Red Blood Cells

The presence of red blood cells in urine, either microscopic or visible grossly, is called hematuria. Hematuria can be transient and benign or, alternatively, signal a disease of the kidneys or urogenital tract. Microscopic hematuria is defined as 2 or more red blood cells per high-powered field in a spun urine sediment on 2 separate urine examinations. Red cell morphology is useful to help localize the source of injury or disease within the kidneys or elsewhere in the urinary system. Monomorphic red cells, which appear round and uniform like those seen on a peripheral blood smear, typically suggest extrarenal bleeding (Figure 14.3). In contrast, dysmorphic red cells often indicate a renal lesion, in particular a glomerular process. The morphology of dysmorphic red cells is characterized by blebbing, budding, and partial loss of the cellular membrane. Acanthocytes are 1 form of dysmorphic red cell that have a ring form with vesicle-shaped protrusions (Figure 14.4). This process results in altered red cell size (smaller) and shape. Monomorphic and dysmorphic red cells may be difficult to distinguish on routine urine microscopy. Phase contrast microscopy and scanning electron microscopy of urine more accurately identify red cell morphology but are not routinely available in most clinical settings. Persistent hematuria most often signals nephrolithiasis, glomerular pathology, or malignancy of the kidneys or urinary tract.

Related posts:

Introduction Urinary Tract Infection Diuretics Disorders of Water Balance-Hypo and Hypernatremia Acute Kidney Injury Guiding Questions

Stay updated, free articles. Join our Telegram channel

Join