Usefulness of Macroscopic Urinalysis as a Screening Procedure A Preliminary Report G. BERRY SCHUMANN, M.D., AND NANCY F. GREENBERG, B.S. Schumann, G. Berry, and Greenberg, Nancy F.: Usefulness of macroscopic urinalysis as a screening procedure. A preliminary report. Am J Clin Pathol 71: 452-456, 1979. The macroscopic examination (physicochemical testing) is a sufficient laboratory screening procedure for routine urinalyses when accurately assessed. Only in those patients for whom routine urine specimens are macroscopically positive or in symptomatic patients with or without known renal or urinarytract disease should a microscopic examination be necessary. Results of this study of more than 900 consecutive routinely screened urine specimens indicate that there is less than a 3% diagnostic yield when the urine sediment is examined after a negative macroscopic examination. (Key words: Macroscopic and microscopic urinalysis.) Materials and Methods Initially, 910 fresh, early-morning, clean, voided, midstream urine specimens were examined within one hour after being received in the microscopy section at Upstate Medical Center. In this study clean-catch urine specimens were not refrigerated after collection, and preservatives or fixatives were not used. The majority of the patients were from hospital admissions, clinics, or the emergency room. Patients under the care of the nephrology, urology, or renal transplant services were excluded, since the majority of these urine specimens were from symptomatic patients and were examined by their own physicians. A reagent-strip* was used for chemical testing (glucosuria, proteinuria, etc.), and urinary color, appearance, and specific gravity were evaluated by the microscopy technologists. A conventional unstained brightfield microscopy examination was performed after centrifugation of 10 ml of the urine specimen (2,000 rpm x 5 min).' In a second study, 102 consecutive clean-catch urine specimens from both asymptomatic and symptomatic subjects were evaluated for accuracy in describing urinary appearance (turbidity). Samples of the original 102 urine specimens were reexamined for turbidity after results of microscopic examination were recorded. Turbidity was determined by the ability to read newspaper print through the urine while it was in a transparent, conical centrifuge tube. In a third study, 220 reagent-strip-negative urine specimens from asymptomatic and symptomatic subjects were examined by microscopy after their appearance (turbidity) was determined by nephelometry.t The purpose of this study was to correlate various amounts of urinary sediment with an accurate measurement of turbidity. The majority of these 220 urine specimens were visually clear or slightly cloudy. "Normal" values for formed elements vary from one laboratory to another. The morphojogic criteria used Received June 27, 1977; accepted for publication April 6, 1978. Technical assistance funded by Ames Co. (Division of Miles Laboratories), Elkhart, Indiana 46514. Address reprint requests to Dr. Schumann: Director of Cytopathology, University of Cincinnati Medical Center, Cincinnati, Ohio 45229. * Multistix, Ames Co. (Division of Miles Laboratories), Elkhart, Indiana 46514. t Amylase and Lipase Analyzer, Perkin-Elmer, Coleman Instrument Division, Oak Brook, Illinois 60521. 0002-9173/79/0400/0452 $00.75 © American Society of Clinical Pathologists 452 Downloaded from http://ajcp.oxfordjournals.org/ by guest on March 6, 2016 THE EXAMINATION OF URINE is the most common screening laboratory procedure utilized for the early detection of renal or urinary-tract disease in asymptomatic subjects. The complete urinalysis 1 involves (1) macroscopic evaluation of color, appearance (turbidity), specific gravity, reagent-strip and tablet chemical tests, and (2) microscopic examination. The latter analysis is tedious and requires experience, and many times a more detailed evaluation is necessary. 3 - 7 A major question concerning all routine urinalysis laboratories is the diagnostic yield of a procedure in screening urine specimens from asymptomatic individuals. We feel that macroscopic examination is a sufficient screening test for routine urinalyses, and in this study we evaluate the need of a routine microscopic analysis on a macroscopically negative urine. Division of Clinical Pathology, Department of Pathology, Upstate Medical Center, Syracuse, New York Vol. 71 . No. 4 453 SCREENING MACROSCOPIC URINALYSIS Table 3. Positive Findings by Microscopy in 54/555 Urine Specimens Negative by Multistix Reagent Strip Tests Table I. Criteria for Classification of Positive Microscopic Results Using Brightfield Microscopy 1,2 Urine sediment must contain one of the following: (1) >5 erythrocytes, leukocytes, or renal tubular cells per highpower field (x 430) (2) > 3 hyaline casts, > 1 granular cast or presence of any other type of cast per low-power field (x 100) (3) > 1 + bacteria per high-power field (x 430) (4) Presence of fungi, parasites, or viral inclusions (5) Presence of significant crystals (e.g., cystine) or a large number of crystals (e.g., uric acid) to establish positivity or abnormality of a urine sediment by unstained brightfield microscopy is shown in Table l.1-2 The percentages of urine specimens with proteinuria, hemoglobinuria, glucosuria, or bilirubinuria that also had positive microscopic findings are presented in Table 2. Of the 910 urines examined, 20% (184) had proteinuria. The distribution of the amounts of proteinuria was: 95 (trace); 41 (1+); 29 (2+); 23 (3+); 2 (4+). Of these 184 urines with proteinuria, 6 1 % (112) had positive microscopic findings. Seven per cent (62/910) had glucosuria and 45% (28/ 62) had positive microscopic results. The distribution of the amounts of glucosuria as measured by the Ames Clinitest was: 20 (trace); 10 (1+); 8 (2+); 8 (3+); 15 (4+). Hemoglobinuria was present in 107 (12%) of the urine specimens (Ames Hemastix), and 65% (70/107) of these had positive microscopic findings. Two urine specimens (0.2%) had bilirubin (Ames Icotest), and for both of these microscopic findings were also positive. Approximately 10% (54/555) of the routinely screened urinary specimens yielded positive results on microscopic examination with a negative macroscopic examination (Table 3). Bacteriuria and pyuria were the most common abnormalities. None of the 54 urine specimens had more than eight erythrocytes or renal epithelial Table 2. Percentage of Positive Brightfield Microscopy Results (910 Routine Urine Specimens) Positive Findings Reagentstrip Results Macroscopic Microscopic No. % No. % Proteinuria Glucosuria Hemoglobinuria Bilirubinuria 184/910 62/910 107/910 2/910 20 7 12 0.2 112/184 28/62 70/107 2/2 61 45 65 100 Erythrocytes* Castst Bacteriuria and pyuria Renal epithelial cells Trichomonads and yeasts 3 12 27 9 3 * No specimen had more than 8 erythrocytes per high-power field; 99ft of the urine specimens with >5 erythrocytes per high-power field were detected by Ames Hemastix. t in most of the 12 specimens, the casts were hyaline type; rarely, granular type. cells per high-power field. Most of the 12 specimens with casts were of hyaline type or a rare granular type. The specimens with trichomonads and yeasts present had scant to few numbers of these organisms. In the second study describing urinary appearance, 21/102 (21%) of the specimens were reported as clear, but upon reexamination in a transparent, conical centrifuge tube, they were, in fact, turbid. Furthermore, 3/102 (3%) urines that we considered clear were reported as turbid by the microscopy section. Turbidity was attributed to pyuria and/or bacteriuria in 13/21 (62%) Table 4. Correlation of Positive Microscopic Urinalysis Results from 220 Reagent-strip-negative Urine Specimens with Various Degrees of Turbidity by Use Nephelometry (%) Distribution of 200 Urine Specimens Distribution of 39 Microscopically Positive Urine Specimens 3 4 5 6 7 8 9 10 11 12 13 14 8 24 35 36 35 23 11 9 7 3 4 5 0 0 2 2 3 7 4 2 3 0 2 1 3 2 2 2 2 1 0 2 3 4 2 1 3 3 1 0 Turbidity Visual detection of turbidity 15 16 17 18 19 20-25 25-50 50-75 75-100 Downloaded from http://ajcp.oxfordjournals.org/ by guest on March 6, 2016 Results Microscopic Finding Urine Specimens (No.) A.J.C.P. • April 1979 SCHUMANN AND GREENBERG 454 Table 5. Interpretations of 39 Positive Microscopic Results Following Turbidity Determi nations Microscopic Results Urine Specimens (No.) Turbidity <%) 1 5.0 2 5.5 3 6.0 4 Epithelial Cells Mucus Bacteria Leukocytes Erythrocytes Per HPF* 1+ 6.0 Casts Miscellaneous Per LPFt 10 hyaline 15 2 7 4 1 1 Interpretation Dehydration 1 spermatozoon; 1 trichomonad vet Nonspecific J 4 hyaline ( 1 granular Dehydration 12 4 VC Trace 5 7 VC 1+ 1+ 15 3 1+ Trace 1 1 8.0 2+ 10 12 10 8.0 1+ 20 11 8.0 2+ 1+ 10 2 VC 12 8.0 2+ 1+ 15 1 VC 13 10 1 VC 1+ 30 2 VC 2+ 10 1 UTI 7.0 7.5 7 7.5 8 8.0 9 1+ 1+ 1+ VC 1 hyaline Trace yeast 1 2 granular | 1 epithelial VC UTI§ UTI 8.5 1+ 14 8.5 1+ 15 9.0 16 9.0 2+ 10 2 VC 17 9.0 1+ 20 1 VC 18 9.0 1+ 3 1 2 hyaline j 1 epithelial VC Trace yeast 19 10.0 1+ 2+ 5 2 VC 20 10.0 1+ 2+ 7 2 VC 21 11.0 1+ 30 8 Pyuria 22 11.0 8 2 23 11.0 1+ 50 1 Pyuria 24 13.0 2+ 15 5 VC 25 13.0 2+ 1 6 26 14.0 1+ 10 2 VC 27 15.0 3+ 2 4 UTI 28 15.0 Trace 1 1 29 16.0 Trace 3+ 3 0 VC 30 18.0 3+ 2+ 2 2 VC 31 18.5 2+ 1+ 5 8 1+ 2+ 2+ Amorphous urates j 1+ Calcium ) ( oxalate crystals | J 1 hyaline j 1 granular VC VC Dehydration 1 hyaline j 1 granular VC TrichomonadsJ 32 19.0 2+ 1+ 1 1 VC Downloaded from http://ajcp.oxfordjournals.org/ by guest on March 6, 2016 5 6 455 SCREENING MACROSCOPIC URINALYSIS Vol. 71 • No. 4 Table5. {Continued) Microscopic Results Urine Specimens (No.) Turbidity (%) 33 20.5 34 22.0 35 23.0 36 27.0 35.0 37 38 39 Epithelial Cells Mucus Bacteria Leukocytes Erythrocytes Casts Miscellaneous 50 2+ Pyuria UTI 25 7 granular I epithelial 3+ 4+ 15 20 39.0 1+ 80 55.0 3+ 20 1+ ' HPF, high-power field. !" LPF, low-power field. ? Renal disease UTI UTI UTI UTI $ VC. vaginal contamination. § UTI, urinary-tract infection. tive, 9.7% were microscopically positive by the criteria in Table 1. When turbidity is considered a positive macroscopic index, the results of our study showed that in 16/155 (2.9%) findings were positive on microscopic examination after negative macroscopic results. Discussion Studies of the diagnostic usefulness and efficiency of screening routine urine specimens are scant to nonexistent. 26 Development of a new approach for evaluating urinary sediment as a special procedure and complementary diagnostic tool has been of interest to us. Recently, we have become concerned with the amount of time spent examining essentially negative urine specimens. Macroscopic examinations should be utilized for screening of specimens to be submitted for microscopic analysis. Only those specimens with turbidity, proteinuria, glucosuria, hemoglobinuria, or bilirubinuria should Table 6. Calculation of the Diagnostic Yield of a Routine Microscopic Urine Examination Following a Negative Macroscopic Analysis Total Number Routine urines Reagent-strip* positive urine specimens Reagent-strip negative urine specimens Microscopically positive urine specimens from Multistix reagent-strip negative specimens Microscopically positive urine specimens from Multistix reagent-strip and visually clear negative urine specimens 1 910 355 555 54/555 (9.77r) 16/555 (2.97r) Multistix, Ames Co. (Division of Miles Laboratories), Elkhart, Indiana 45414. Downloaded from http://ajcp.oxfordjournals.org/ by guest on March 6, 2016 and amorphous urates or phosphates in 6/21 (29%) of the specimens. Results of the third study involving the microscopic examination of the 220 reagent-strip-negative urine specimens following nephelometric determinations of turbidity are presented in Table 4. The majority of specimens had turbidometric measurements between 4 and 11%. In total, 39 had positive urinary sediment findings (Table 5). Below the 8% turbidity level, there were 138/220 (63%) specimens with negative reagent-strip reactions. Of the 138 specimens, only seven had positive results on microscopic examination. Of these seven, two represented dehydration by the increased numbers of hyaline casts; the others represented vaginal contamination. Above the 8% turbidity level, the number of positive sediment findings increased. Between 8 and 15% turbidity level, there were 17 positive sediment findings. We found evidence of urinary tract infection in three, pyuria in two, and the remainder represented vaginal contamination. The criteria for vaginal contamination were based on the presence of superficial squamous epithelial cells, mucus, and cellular debris in a female patient.' Above the 15% turbidity level (the level where turbidity is visually detectable), 11/17 specimens (65%) had positive urinary findings. After discarding specimens interpreted as vaginal contamination, 7/11 (64%) were probably diagnostic of renal or urinary-tract disease. The diagnostic yield or false-negative rate of a positive microscopic examination of urine following a negative macroscopic examination is shown in Table 6. Thirty-nine per cent (355/910) of the routine urines in this study were reagent-strip (Multistix)-positive. Of the remaining specimens that were reagent-strip-nega- Interpretation 456 SCHUMANN AND GREENBERG The development of strict guidelines for urine specimen collection and processing can reduce problems such as vaginal contamination and bacterial overgrowth. Use of (1) a more comprehensive reagent-strip that tests for nitrite (bacterial growth) and microhematuria and (2) an accurate measurement of turbidity would significantly improve the usefulness of the macroscopic examination as a screening tool. By defining clinically significant abnormalities, a better assessment of falsenegative results can be obtained. From the results of this preliminary study, we conclude that there is less than a 3% false-negative rate (Table 6) when the urine is examined microscopically after a negative macroscopic examination. Urinarytract infection, pyuria, and dehydration were the only suggested diagnoses, and probably these patients were symptomatic at the time (Table 5). Furthermore, urine cultures and antibody-coated bacterial studies3,8 would have been more helpful in establishing the correct diagnosis. At present, it appears that the macroscopic analysis in itself is a sufficient screening method. References 1. Bradley GM, Benson ES: Examination of the urine, Todd-Sanford Clinical Diagnosis by Laboratory Methods. 15th edition. Edited by Davidsohn I, Henry JB. Philadelphia, W. B. Saunders, 1974, pp. 15-81 2. Heimann GA, Forhlich J, Bernstein M: Physician's response to abnormal results of routine urinalysis. Can Med Assoc J 115:1094-1095, 1976 3. Jones SR, Smith JW, Sanford JP: Localization of urinary-tract infections by detection of antibody-coated bacteria in urine sediment. N Engl J Med 290:591-593, 1974 4. Musher DM, Thorsteinsson SB, Airula UM: Quantitative urinalysis, Diagnosing urinary tract infection in men. JAMA 236: 2069-2072, 1976 5. Schumann GB, Harris S, Henry JB: An improved technic for examining urinary casts and a review of their significance. Am J Clin Pathol 69:18-23, 1978 6. Schumann GB, Henry JB: An improved technique for the evaluation of urine sediment. Lab Management 15:18-24, 1977 7. Sternheimer R: A supravital cytodiagnostic stain for urinary sediments. JAMA 231:826-832, 1975 8. Thomas U, Shelokov A, Forland M: Antibody-coated bacteria in the urine and the site of urinary-tract infection. N Engl J Med 290:588-590, 1974 Downloaded from http://ajcp.oxfordjournals.org/ by guest on March 6, 2016 be examined microscopically. Microscopic analysis should also be done on those specimens from symptomatic patients or those with known renal disease even when a macroscopic examination is negative. Since many of these patients are monitored daily, urinary sediment evidence of progressive urinary system disease or response to therapy can be evaluated. An accurate assessment of turbidity must be made for each urine specimen. Nephelometry was used to determine turbidity objectively. Although not routinely used in the microscopy laboratory, we found it to be of great value in predicting the amounts of formed elements in urine. Inspection of urine specimens in the original containers explained many turbidity misinterpretations. We found that 21/102 (21%) of the urines were reported as clear, but were indeed cloudy. If an accurate assessment of turbidity had been made in our initial study, many of the 54 urines called negative macroscopically would have been classified as positive macroscopically. The five most common causes of turbidity in these urines were leukocytes, erythrocytes, epithelial cells, bacteria, and amorphous material. Prospective studies (unpublished data) comparing unstained brightfield microscopy with a new cytocentrifugation/Papanicoloau stain technic have consistently shown discrepancies in the morphologic interpretation of 10-25% of the urines.6 In examining more than 3,000 urine sediments, we have found the latter to be diagnostically superior.6 Although we are not recommending this particular technic for routine screening, we feel that further evaluation of the urine by "special" procedures is needed. In random screenings such as those in physical examinations for insurance purposes, hospital admissions, etc., much time and expense could be saved by omitting the microscopic examination on those urine specimens that are yellow and clear and have a negative chemical reaction to the reagent strip. Currently, we are continuing to evaluate the efficacy of accurate physicochemical testing in screening routine clean-catch urines from asymptomatic subjects. A.J.C.P. • April 1979