Clinical and Interpretive

Urinalysis is useful for screening for urinary tract diseases and some nonrenal diseases.

The kidney plays a key role in the excretion of by-products of cellular metabolism and regulation of water, acid-base, and electrolyte balance. Urine is produced by filtration of plasma in the renal glomeruli, followed by tubular secretion and/or reabsorption of water and other compounds.

Abnormalities detected by urinalysis may reflect either urinary tract diseases (eg, infection, glomerulonephritis, loss of concentrating capacity) or extrarenal disease processes (eg, glucosuria in diabetes, proteinuria in monoclonal gammopathies, bilirubinuria in liver disease).

Osmolality is an index of the solute concentration of osmotically active particles, principally sodium, chloride, potassium, and urea; glucose can contribute significantly to the osmolality when present in substantial amounts. The ability of the kidney to maintain both tonicity and water balance of the extracellular fluid can be evaluated by measuring the osmolality of the urine. More information concerning the state of renal water handling or abnormalities of urine dilution or concentration can be obtained if urinary osmolality is compared to serum osmolality. Normally, the ratio of urine osmolality to serum osmolality is 1.0 to 3.0, reflecting a wide range of urine osmolality.

In a random urine specimen, a protein/creatinine or protein/osmolality ratio can be used to roughly approximate 24-hour excretion rates.

UA also detects the presence of overt proteinuria (>300 mg/day). Normal urinary protein excretion is <30 mg/day. The presence of microalbuminuria (30-300 mg/day) is not detected by this method. Overt proteinuria is seen in both renal (eg, glomerulonephritis, renal tubular diseases, pyelonephritis) and nonrenal diseases (eg, myeloma, congestive heart failure, dehydration).

In the measurement of glucose, no other substance excreted in urine is known to give a positive result, including other reducing substances (eg, galactose, fructose, and lactose). This test may be used to determine whether the reducing substance found in urine is glucose. Glucosuria occurs when the renal threshold for glucose is exceeded (typically >180 mg/dL); this is most commonly, although not exclusively, seen in diabetes.

Urine pH is affected by diet, medications, systemic acid-base disturbances, and renal tubular function. pH may affect urinary stone formation. For example, urine pH <6.0 may help reduce the tendency for calcium phosphate stones and pH >6.0 may reduce the tendency for uric acid stone formation.

Produced during metabolism of fat, increased ketones may occur during physiological stress conditions such as fasting, pregnancy, strenuous exercise, and frequent vomiting. In diabetics who are unable to efficiently utilize glucose due to a lack of insulin, starvation, or with other abnormalities of carbohydrate or lipid metabolism, ketones may appear in the urine in large amounts before serum ketone is elevated.

Bilirubinuria is an indicator of liver disease and biliary tract obstruction.

Hemoglobinuria is an indicator of intravascular hemolysis. The test is equally sensitive to myoglobin as to hemoglobin. The presence of hemoglobin, in the absence of RBCs, is consistent with intravascular hemolysis. RBCs may be missed if lysis occurred prior to analysis; the absence of RBCs should be confirmed by examining a fresh specimen.

Urine can contain a variety of reducing substances (sugars [glucose, galactose, sucrose, fructose, lactose, maltose], ascorbic acid, drugs, etc), compounds so termed because of their ability to reduce cupric ions. The primary reducing substances of medical significance are the sugars, glucose (diabetes), and galactose (galactosemia). Other sugars may be found but are not of clinical significance. Because glucose also is detected by glucose-specific dipstick reagents, the test for reducing substances is performed to detect galactose.

RBCs, WBCs, renal tubular epithelial (RTE) cells, transitional epithelial cells, squamous epithelial cells, casts, sperm, free fat, oval fat bodies, bacteria, and pathologic crystals are reported and if are present in significant quantities, urine microscopy is reflexed. RBC casts are almost always indicative of glomerulonephritis. White cell casts are typically an indication of acute interstitial nephritis or pyelonephritis, but can also be seen in glomerulonephritides because there is often a component of accompanying interstitial nephritis. Fatty casts and free fat are often seen in patients with nephrotic syndrome or other glomerular diseases associated with significant proteinuria. Granular casts are observed in a number of disorders and are thought to be formed from partially degraded cellular casts, or are protein-derived casts. Hyaline casts are not thought to be indicative of any disease process, but increased numbers may be seen in concentrated urine specimens. Waxy casts and broad casts are most often observed in advanced renal failure. Increased numbers of RTE cells are indicators of renal tubular injury. Increased numbers of RTE may be caused by drugs with renal tubular toxicity (eg, cyclosporine A, aminoglycosides, cisplatin, radio-contrast media, acetaminophen overdose), interstitial nephritis, hypotension (surgical, sepsis, obstetric complications), or heme pigments from hemoglobinuria or myoglobinuria from rhabdomyolysis (eg, alcoholism, heat stroke, seizures, sickle cell trait). Newborns often shed RTE cells in their urine. The presence of squamous cells suggests that the specimen may not have been an optimal clean-catch specimen and could be contaminated with skin flora.

Caution should be taken in interpretation of the following:

Glucose:
-Urine glucose monitoring for the management of diabetes mellitus has essentially been replaced by more accurate and reliable fingerstick blood glucose determination. Also, as a screening test for diabetes mellitus, urine glucose testing has a low sensitivity (though reasonably good specificity).
-Drugs: No interference was found at therapeutic concentrations using common drug panels.-Normal neonatal infants during the first 10 to 14 days of life may excrete urine giving a positive reaction due to glucose, galactose, lactose, and fructose. The hexokinase method on the chemistry analyzer is specific for glucose only.

Ketones:
-Substances causing false-positive results are bromsulphalein, phenolsulfonphthalein, phenylketone, cephalosporin, aldose-reductive antienzyme, and L-Dopa.-Fasting or starvation diets may cause positive results.

Hemoglobin:
-Elevated specific gravity, elevated protein, and large amounts of ascorbic acid may cause false-negative results.
-Oxidizing substances such as hypochlorite and chlorine may cause false-positive results.
-The test is equally sensitive to hemoglobin and myoglobin. The presence of hemoglobin, in the absence of RBCs, is consistent with intravascular hemolysis. RBCs may be missed if lysis occurred prior to analysis; the absence of RBCs should be confirmed by examining a fresh specimen.

Protein:
-False-positive results may be obtained with highly buffered, alkaline urines and large amounts of hematuria.
-Contamination of the urine specimen with quaternary ammonium compounds (eg, from some antiseptics and detergents) or with skin cleansers containing chlorhexidine also may produce false-positive results.
-Microalbumin tests are necessary to pick up early increases in urine protein excretion.

Reducing Substances:
-This test reacts with sufficient quantities of any reducing substance in the urine; it is not specific for glucose.
-Low specific gravity urines containing glucose may give slightly elevated results.
-Metabolites of some sulfa drugs and methapyrilene compounds may interfere with the sensitivity of the test.
-X-ray contrast media in urine produces reduced and false-negative glucose results.