Urinalysis of Pathologic Conditions
Urinalysis is a quick and cost-effective method for the screening, diagnosis and monitoring of many pathological disorders of the urinary system.
A urinalysis is an important and cost-effective laboratory test for the assessment of kidney dysfunctions when the specimen is collected, processed and analyzed correctly. Although it's used most frequently as a screening test, it can also be utilized for monitoring response to treatment or progression of a disease state.
Implementation of a quality control (QC) program and correlation of chemical test results (dipstick) with physical characteristics and microscopic examination are necessary if the clinician and patient are to benefit from test results. With this as the goal, it's necessary to review several important concepts of accurate test performance before urinalysis results can be applied to pathologic conditions.
Significance of Urinalysis
A preanalyzed urine control should be used for both dipstick and microscopic examination of urine sediment to ensure accuracy, sensitivity and specificity of the dipstick reagent areas and recognition of select microscopic sediment. Correlation of chemical test results with physical characteristics and microscopic sediment is an extension of QC and important in reporting valid results.
Specimen collection and processing are the first steps in providing accurate test results. A clean, midstream urine specimen should be collected and processed within one hour to inhibit changes in the physical, chemical and microscopic sediment due to deterioration. Effects of deterioration include:
* an increase in turbidity due to solute precipitation and bacterial multiplication;
* decomposition of urea by bacteria, giving an ammonia odor and an increase in pH; and
* color that will darken due to the oxidation/reduction of bilirubin and urobilinogen.
Although a pH of eight or greater usually indicates an old specimen, urine will become more alkaline upon standing, resulting in decreased sensitivity and specificity of other reagent areas on the dipstick and a loss of sediment that may be important in the diagnosis of a specific disorder. If glucose is present, the urine may become more acidic due to the conversion of glucose to alcohol and acids by bacteria. In this situation, urine sediment will be preserved.
There are differing opinions of the necessity of microscopic sediment examination on all specimens sent to the laboratory. Many labs are using macroscopic screening as a time-saving and cost-effective measure. With macroscopic screening, if either the protein, glucose, nitrite or blood is positive on the dipstick, a microscopic examination is warranted. When using these parameters, it's highly recommended that the pH and specific gravity be considered when correlating results (Table 1). This is an important consideration in the correlation of dipstick reactions, microscopic sediment and specific characteristics of some pathological conditions.
One of the first indicators of a renal disorder is the persistent presence of proteinuria (that may be accompanied by other positive reagent areas) and abnormal sediment. Accurate sediment identification is important in the diagnosis of kidney disorders and laboratory personnel should maintain a high level of expertise. Epithelial cells should be identified as renal, transitional or squamous and the number of each reported since the type of cell may indicate the location of the disease or disorder. Of the three types, renal epithelial cells are the most significant and the only one that can be found in a cast.
Differentiation of renal and transitional epithelial cells is one of the more difficult tasks in the performance of the microscopic examination. Since the renal epithelial cell is found only in the tubules of the nephron, their presence in increased numbers is frequently indicative of glomerulonephritis or an inflammatory process.
Most white cells in the urine are neutrophils; however, lymphocytes, monocytes and eosinophils may be present but not identified. If these cells are recognized they should be reported-they may indicate a specific condition. For example, lymphocytes are usually present in acute pyelonephritis and in renal transplant patients and are often an early indicator of rejection. Monocytes may be mistakenly identified as renal tubular epithelial cells or overlooked and yet indicate viral involvement. Eosinophils are seen in patients with acute interstitial nephritis and allergic reactions.
Casts are formed in acid urine when there's increased solute concentration and decreased urine flow. Since these conditions are frequently present in healthy patients, hyaline and granular casts may be present normally as well as in pathologic conditions. Other types of casts-red and white blood cells, renal tubular epithelial, fatty, waxy and bacterial casts-are significant and, therefore, should be distinguished and the number of each reported. Broad casts of any type should always be reported since they indicate the state of the tubule in which the cast was formed and usually chronic or end stage kidney disease.
Fatty casts, oval fat bodies and free fat globules are characteristic sediment of the nephrotic syndrome patient; red cell casts are a significant indicator of acute glomerulonephritis; and white cell casts indicate acute pyelonephritis. These disorders, their characteristic urinalysis results and additional laboratory supporting tests are summarized in Table 2.
Renal disorders may be classified as general categories based upon the function of the kidney. The categories include:
1) glomerular function, which is frequently immune mediated,
2) tubular function and interstitial involvement as a result of an infection or toxic agent and
3) vascular disorders resulting in decreased renal perfusion and subsequent morphological and functional changes.
Glomerulonephritis may be termed primary or secondary to another condition. Acute, crescentic, membranous, focal/segmental and chronic glomerulonephritis are examples of primary glomerular disorders. (Only acute and chronic glomerulonephritis will be discussed since urinalysis is not significantly involved in the differentiation of the other types of glomerulonephritis.)
Secondary glomerulonephritis occurs as a result of a systemic disease such as lupus erythematosus, diabetes mellitus or amyloidosis. Morphological characteristics include:
* an increase in the number of endothelial and epithelial (podocyte) cells;
* leukocyte infiltration involving neutrophils and macrophages;
* basement membrane thickening of immune complex reactions and fibrin products and
* hyalinization with sclerosis and eosinophilic material accumulating in the glomerulus.
Acute glomerulonephritis patients usually present with fever, malaise, nausea, edema and hypertension. Dipstick results indicate the presence of hematuria, proteinuria or pyuria. Microscopic examination of the sediment will reveal the presence of predominately red blood cells and red cell casts. Some of the red cells may be dysmorphic, indicating that the blood is from the glomeruli. White cells, renal tubular epithelial cells, hyaline and granular casts will also be present but in fewer numbers than red cells and red cell casts.
Other laboratory tests correlating with these results include an increased anti-streptolysin O titer (ASOT), blood urea nitrogen (BUN)/creatinine ratio and the presence of cryoglobulin. The creatinine clearance and complement will be decreased. Children may recover from acute glomerulonephritis spontaneously or with minimal treatment, whereas 60 percent of adults recover and the remaining 40 percent progress to chronic glomerulonephritis.
In chronic glomerulonephritis, the patient may have many of the same symptoms but have a decrease in renal function as the glomeruli become hyalinized. Urinalysis results tend to be more variable with a decrease in concentration of the typical glomerulonephritis microscopic sediment. As the patient's condition continues to deteriorate, all casts become more broad and waxy casts are present. The change in sediment as acute glomerulonephritis progresses to the chronic state re-emphasizes the importance of performing the urinalysis before marked deterioration begins and the necessity of an accurate analysis.
Some glomerulonephritis patients may progress to nephritic or nephrotic syndrome. Patients with nephritic syndrome have proteinuria of less than 2.5 grams per day with clinical symptoms of hypertension, edema, a urine with red cells and red cell casts and a moderate amount of proteinuria. Heavy proteinuria of 3.5 grams per 24-hour period or greater is characteristic of nephrotic syndrome with the urinary sediment remaining the same.
Nephrotic syndrome may be associated with many different diseases or conditions where there is increased passage of plasma proteins (primarily albumin), hypoalbuminemia and edema. Approximately 90 percent of nephrotic syndrome cases can be attributed to glomerulonephritis in children and approximately 75 percent of nephrotic syndrome cases in adults. The most significant findings in urinalysis are heavy proteinuria and the presence of oval fat bodies, free fat globules and fatty, waxy and renal epithelial casts. The presence of fat in the urine may be confirmed in the microscopic sediment by the addition of Sudan III, Sudan IV or Oil Red O. Serum chemistry tests indicate hypoalbuminemia and hyperlipidemia with increased levels of cholesterol, triglycerides, very low density lipoprotein and phospholipid.
Tubular disease may affect a single pathway such as proximal tubule dysfunction involving renal glucosuria or cystinuria. Multiple pathway involvement includes tyrosinemia, Wilson's disease, galactosemia and glycogen storage disease. Routine urinalysis application consists of screening for galactose with Clinitest (Bayer Corp., Tarrytown, NY) or the presence of crystalline sediment such as cystine, leucine or tyrosine in the microscopic sediment.
Acute tubular necrosis is also a tubular disorder and may be classified as ischemic or toxic. In ischemic nephrosis, there's decreased renal perfusion of the kidneys as a result of shock, trauma or sepsis, whereas toxic necrosis may be due to drugs or toxins. A urinalysis indicates mild proteinuria, a positive blood, red and white cells, renal tubular epithelial cells and hyaline, granular, renal tubular epithelial and waxy casts.
Tubulointerstitial disorders may involve infections, toxins, neoplasms, transplant rejection and vascular disorders. Pyelonephritis is the most common disease state in this category and involves the renal tubules, interstitium and renal pelvis. This condition is frequently associated with catheterization, obstruction, pregnancy and diabetes. The glomerulus is rarely involved.
Clinical symptoms consist of flank pain, dysuria, frequency of micturition, fever, headache and nausea. The presence of white blood cells, white cell casts and white cell clumps are characteristic of pyelonephritis. Bacteria, renal tubular epithelial cells, glitter cells and granular, hyaline and epithelial casts may be present. The protein, nitrite, leukocyte esterase and blood reagent areas of the dipstick may be positive.
White cell casts are important in the differentiation of pyelonephritis and cystitis. Since casts are formed in the tubules they won't be present in cystitis, nor will there be an increase in renal tubular epithelial cells in cystitis. The immunofluorescent antibody coated bacteria (ACB) test will be positive in pyelonephritis and can also be used to differentiate between the two disorders.
The urine of chronic pyelonephritis patients will have moderate proteinuria of less than 2.5 grams per 24 hours and a positive leukocyte esterase. White blood cells, macrophages, glitter cells and renal tubular epithelial cells may be present but are fewer in number than in the acute stage. Hyaline, granular and white blood cells casts will also tend to be more broad than in the acute stage.
Microscopic examination of urine is important in the evaluation of acute interstitial nephrosis where the presence of eosinophiluria may confirm a tentative diagnosis. The condition is frequently the result of an allergic reaction to drugs such as penicillin or sulfa medications.
The interstitium is endemic and infiltrated with white blood cells, especially lymphocytes, eosinophils and some macrophages. Dipstick results may indicate a urine protein of less than one gram per 24 hours and a positive leukocyte esterase. This will correlate with sediment results but may be found in other conditions and is not indicative of acute interstitial nephritis.
Clinical symptoms of cystitis are lower abdominal discomfort, pain on urination, fever and general malaise. A positive blood, leukocyte esterase and nitrite will be found on the dipstick red and white blood cells, transitional epithelial cells and some histiocytes may be present in the microscopic. The absence of casts clearly differentiates between cystitis and pyelonephritis.
Urinalysis is frequently underestimated as a quick and cost-effective method for the screening, diagnosis and monitoring of many pathological disorders of the urinary system. A minimal amount of time is required for specimen analysis and provides immediate feedback to the clinician who can initiate treatment and provide better health care for the patient. To provide accurate results, a quality assurance program encompassing the use of controls, standardized procedures for test performance and correlation is necessary.
Dr. Conrad is chair, Department of Medical Technology, Wichita (KS) State University.
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