THE SIGNIFICANCE OF PYURIA
Pyuria is an important laboratory parameter in two different settings:
It is extremely important in the assessment of bacterial infection of the urinary tract because it is present in almost all such infections, and its absence must suggest another diagnosis.
It is present as a nonspecific reaction to inflammation of the urinary tract. The differential diagnosis for sterile pyuria is therefore a broad one.
Pyuria is often arbitrarily defined as the presence of more than 10 leukocytes per high-power microscopic field from a centrifuged specimen. This method clearly represents only a crude quantitative assessment for several reasons: (a) Initial urine volumes are variable, (b) centrifugation is not standardized with respect to time or speed, (c) the amount of urine placed on a slide is variable, and (d) with no grid for reference, observer bias occurs regarding the area in which cells are to be counted. Several methods for quantifying pyuria are more accurate and useful in clinical studies, though impractical for office evaluation. Measurement of pyuria as the leukocyte excretion rate has been used as a more accurate quantitative method. Hourly rates of leukocyte excretion above 400,000 correlate with symptomatic urinary tract infection. By means of hemocytometer measurement of pyuria, a leukocyte count of more than 10/mm3 has been correlated with more than 105 bacteria per colony-forming unit.
More recently, the use of rapid methods to determine pyuria has become widespread. Measurement of leukocyte esterase, an enzyme in neutrophil granules, can be determined within 1 to 2 minutes by using an enzyme-impregnated dipstick. This measurement correlates well with significant pyuria defined as more than 10 WBCs per cubic millimeter of urine. In one study, the test had a 50% positive predictive value for bacterial infection but a negative predictive value of 92%.
Stamm (1983) concluded that accurate estimation of pyuria is important for the following reasons: (a) A leukocyte count of 10/mm3 or more occurs in fewer than 1% of asymptomatic, nonbacteriuric patients but in more than 96% of symptomatic patients with significant bacteriuria; (b) most symptomatic women with pyuria but without significant bacteriuria do have urinary tract infection, either with uropathogens at a level below 105/mL or with Chlamydia trachomatis; (c) patients with catheter-associated bacteriuria and pyuria are more likely to have true infection. Several studies in spinal cord-injured patients with indwelling catheters have confirmed that pyuria is a risk factor for increased morbidity secondary to untreated urinary tract infection.
Ouslander et al. (1996) recently studied pyuria among incontinent but otherwise asymptomatic nursing home residents. Pyuria was defined as more than 10 WBCs per high-power field. Forty-five percent of the patients studied had pyuria and 43% had bacteriuria. Of the patients with pyuria, only 56% had bacteriuria. Thirty-one percent of bacteriuric patients did not have pyuria. In the patient population studied, pyuria was common regardless of the presence or absence of bacteriuria.
Any inflammatory reaction in the urinary system can result in sterile pyuria of more than 10 WBCs per cubic millimeter of urine or more than 10 WBCs per high-power microscopic field. (The term sterile pyuria has become a common misnomer; it is used to describe pyuria associated with tuberculosis and other infectious processes in which urine cultures for bacteria are negative.) The differential diagnosis for sterile pyuria includes diseases such as perinephric abscess, urethral syndrome, and chronic prostatitis. Fever in association with sterile pyuria must suggest the possibility of renal tuberculosis.
Fungi such as Cryptococcus neoformans and Coccidioides immitis may also cause pyuria and renal infection. Sterile pyuria can occur in chronic prostatitis in that bladder urine will usually contain fewer than 105 bacteria per milliliter of urine. Prostatic secretions will have high numbers of the etiologic agent. Renal papillary necrosis should be suspected in patients with sterile pyuria who have diabetes or sickle cell disease, or who are chronic alcoholics. Urethral inflammation may also cause pyuria. Genital herpes can cause dysuria and pyuria. Infection with C. trachomatis causes an acute urethral syndrome with dysuria and frequency. Patients with perinephric or renal cortical abscesses may present with signs and symptoms of upper urinary tract infection and pyuria but with negative urine cultures.
Other noninfectious causes of pyuria are uric acid and hypercalcemic nephropathy, lithium and heavy metal toxicity, genitourinary malignancy, sarcoidosis, transplant rejection, interstitial cystitis, and polycystic kidney disease. Pyuria may persist for several months after transurethral prostatectomy. (S.L.B.)
Christensen WI. Genitourinary tuberculosis. Review of 102 cases. Medicine (Baltimore) 1974;53:377.
Ninety percent of patients with renal tuberculosis have hematuria or pyuria.
Cos LR, Cocke TT. Genitourinary tuberculosis revisited. Urology 1982;20:111.
Reviews clinical and laboratory features of tuberculosis of the genitourinary tract.
Johnson CC. Definitions, classification, and clinical presentation of urinary tract infection. Med Clin North Am 1991;75:241.
Good brief descriptions of acute urethral syndrome and perinephric abscess.
Kenney M, Loechel AB, Lovelock FJ. Urine cultures in tuberculosis. Am Rev Respir Dis 1960;82:564.
Morning urine specimens are superior to 24-hour collections for isolating Mycobacterium tuberculosis.
Komaroff AL. Urinalysis and urine culture in women with dysuria. Ann Intern Med 1986;104:212.
Describes value of urinalysis (including urine culture and WBC in urine) in various disease states.
Menon EB, Tan ES. Pyuria: index of infection in patients with spinal cord injuries. Br J Urol 1992;69:144.
Spinal cord patients with indwelling catheters who have more than 100 WBCs per high-power field are more likely to have morbidity from urinary tract infection.
Murray T, Goldberg M. Analgesic abuse and renal disease. Annu Rev Med 1975;26:537.
Discusses analgesic nephropathy as a cause of sterile pyuria.
Norman DC, Yamamura R, Yoshikawa TT. Pyuria: its predictive value of asymptomatic bacteriuria in ambulatory elderly men. J Urol 1986;135:520.
Pyuria in an elderly, ambulatory population was highly predictive of the presence or absence of significant bacteriuria.
Ouslander JG, et al. Pyuria among chronically incontinent but otherwise asymptomatic nursing home residents. J Am Geriatr Soc 1996;44:420.
Prevalence of pyuria and its relationship to bacteriuria was determined. Pyuria was common in patients with and without bacteriuria.
Pappas PG. Laboratory in the diagnosis and management of urinary tract infections. Med Clin North Am 1992;75:313.
Describes laboratory methods for defining pyuria.
Patterson JE, Andriole VT. Renal and perirenal abscesses. Infect Dis Clin North Am 1987;1:907.
Renal abscesses can cause pyuria without positive cultures. Corticomedullary abscesses usually are a complication of reflux or obstruction.
Pels RJ, et al. Dipstick urinalysis screening of asymptomatic adults for urinary tract disorders. II. Bacteriuria. JAMA 1989;262:1221.
Describes the leukocyte esterase screening test and its correlation with WBCs in urine.
Petersen EA, et al. Coccidioidouria: clinical significance. Ann Intern Med 1976;85:34.
Discusses infection with C. immitis as a cause of sterile pyuria.
Pfaller MA, Koontz FP. Laboratory evaluation of leukocyte esterase and nitrite tests for the detection of bacteriuria. J Clin Microbiol 1985;21:840.
Reports a 92% negative predictive value for urinary tract infection when leukocyte esterase screening test is used.
Randall RE, et al. Cryptococcal pyelonephritis. N Engl J Med 1968;279:60.
Discusses infection with C. neoformans as a cause of sterile pyuria.
Schaberg DR. Approach to the patient with dysuria or pyuria. In: Kelly WN, ed. Textbook of internal medicine, 2nd ed. Philadelphia: JB Lippincott Co, 1992.
Excellent, succinct discussion of infectious and noninfectious causes of pyuria.
Stamm WE. Measurement of pyuria and its relation to bacteriuria. Am J Med 1983;75 (Suppl): 53.
Compares methods of measuring urine leukocytes. Excellent summary of the significance of pyuria and its sensitivity and specificity in several clinical contexts.
Stamm WE, et al. Causes of the acute urethral syndrome in women. N Engl J Med 1980;303:409.
Describes the syndrome of dysuria and pyuria in young women. About a third of the women studied had C. trachomatis infection.
Teklu B, Ostrow JH. Urinary tuberculosis: a review of 44 cases treated since 1963. J Urol 1976;115:507.
Documents sterile pyuria as a frequent finding in renal tuberculosis.
Thorley JD, Jones SR, Sanford JP. Perinephric abscess. Medicine (Baltimore) 1974;53:441.
Review of the clinical and radiographic features of perinephric abscess.