Japanese Guidelines Of The Management Of Hematuria 2013

Open image in new window Do hematuria standards differ by age or gender? [Statement] Red cell count distribution in urine varies with age and gender. However, since the significance of establishing hematuria standards for each group is unclear, more than 20 erythrocytes/µL or 5 erythrocytes/high power field (HPF) is considered to be the definition of hematuria. [Comment] Neither review articles discussing red cell count in the urine from healthy persons [1, 2] nor the American Urological Association (AUA)’s [3] Best Practice Policy concerning asymptomatic microscopic hematuria distinguish between age or gender in their definitions of hematuria. Moreover, Copley described that the normal number of red cells for children and adults is the same [2]. The standard of hematuria is globally defined as more than 5 erythrocytes/HPF in many reports [2, 4]. Japan’s own definitive text—the Standard Guideline for Urinary Sediment examination JCCLS GP1-P4—also states that below 4 erythrocytes/HPF are observed in the urine from healthy men and women [5]. Open image in new window What is the recommended urine collection method for hematuria diagnosis? [Statement] Intense exercise should be avoided before screening. Use of a clean container is recommended. Specification of urine sampling time, such as mid-stream urine, early morning first-void urine or random sample, is also recommended. (Recommendation grade A) [Comment] The Japanese Committee for Clinical Laboratory Standardization (JCCLS) has issued two documents concerning routine urinalysis: Proposed Guideline for the Urinary Reagent Method [1] and Standard Guideline for Urinary Sediment [2]. Generally, a midstream urine sample is used and physical exercise before collection of urine should be avoided as it may cause hematuria or hemoglobinuria. Open image in new window Do urine blood test strips produced by various manufacturers differ in their sensitivity? [Statement] Although data sheets indicate no differences in sensitivity among various urine test strips, some differences were observed when measuring urine samples. [Comment] The Japanese Committee for Clinical Laboratory Standards (JCCLS) defined that 1+ of a urine blood reagent strip should correspond to 0.06 mg/dL of hemoglobin or about 20 erythrocytes/µL in 2004. However, the upper and/or lower limits of 1+ and other ranks (2+ , 3+ , etc.) have not been standardized. Results of a JCCLS investigation using pooled urine samples spiked with hemoglobin showed considerable differences among test strip manufacturers. Open image in new window What is the recommended urine collection method for medical checkup? [Statement] Adding to the methods described in CQ2, 1) utilizing early morning first-void and mid-stream urine and 2) refraining from ingestion of foods rich in ascorbic acid (vitamin C) are recommended. (Recommendation Grade B) [Comment] The fundamentals of urine collection do not change for medical checkups. However, in medical checkups for schoolchildren, collection of early morning first-void urine is indicated to avoid hematuria caused by physical exercise. Since the urine test strip for blood uses the peroxidase-like action of hemoglobin, if a substance with a reduction action exists, it will yield a false negative result. Therefore ingestion of foods rich in ascorbic acid (vitamin C), which is the most frequent reducing substance appearing in urine, should be avoided the night preceding a checkup. Open image in new window Can you distinguish glomerular hematuria from non-glomerular hematuria by morphological analysis of urinary erythrocytes? [Statement] There are various shapes and sizes of urinary erythrocytes in hematuria. Information pertaining to urinary erythrocyte morphology is therefore useful in deciding the origin of hematuria. Even if glomerular hematuria is morphologically suspected, urinary tract disease other than glomerular disease cannot be ruled out. Moreover, not all types of hematuria can be properly classified. As results of the morphological discrimination method vary among examiners, it is recommended that screening follow the Standard Guideline for Urinary Sediment Examination [Japanese Committee for Clinical Laboratory Standard (JCCLS), Document GP1-P4, Proposed Guideline], which is the standard examination method in Japan. [Comment] In non-glomerular hematuria such as hematuria originated from the lower urinary tract, urinary erythrocytes take the form of atrophy or disc and their morphologies are nearly identical although varying somewhat in size. Furthermore, they are most likely to be rich in hemoglobin. Such erythrocytes are called isomorphic RBCs (glomerular type RBCs1). In contrast, erythrocytes in glomerular hematuria often present with various forms of casts, including erythrocyte casts and proteinuria. These erythrocytes most often appear in various forms, such as a doughnut shape with humps or a target shape, in the same specimen, and are called dysmorphic RBCs (non-glomerular type RBSs) (see Footnote 1). Erythrocyte morphology is generally observed and evaluated at the time of urinary sediment examination using a light microscope in Japan, whereas it is often done using a phase-contrast microscope in other countries. Facilities increasingly use a urinary formed-element analyzer using flow cytometry. None of these methods are capable of classifying all types of hematuria. Therefore, non-glomerular hematuria cannot be ruled out even when glomerular hematuria is morphologically suspected. Open image in new window What are the differences between dysmorphic type RBC2 and isomorphic type RBC (see Footnote 2) in the information about urinary erythrocyte morphology acquired by an autoanalyzer? [Statement] In Japan, urinary components that are observed by an autoanalyzer are distinguished as information pertaining to urinary formed elements from the results of urinary sediment examination. A urinary formed-element analyzer using cytometry can discriminate among blood cells, epithelial cells, casts and other formed elements by processing scattered light from particles as well as light signals corresponding to fluorescence intensity. Urinary erythrocytes can be distinguished based on the bias of the particle size distribution curve of discriminated erythrocytes. Taking advantage of the feature that erythrocytes from the glomeruli are generally smaller than those from other sites, it is possible to classify erythrocytes into dysmorphic and isomorphic type RBC depending on shifts in particle size toward the smaller and larger sides, respectively. Making the above classification may not always be possible, as hematuria specimens may contain a small number of erythrocytes, urine properties such as high acid content may be present, or urine may be very hypotonic or the specimen in a poor state of preservation following collection. Additionally, there may be a mixed dysmorphic/isomorphic RBC type. [Comment] The measurement principle of the urinary formed-element analyzer using cytometry is that particle elements are displayed on a scattergram for analysis by measuring their scattering light and fluorescence provoked by laser light after they are stained with fluorochrome for exact characterization of their sizes, shapes and nuclei. This analytical method can characteristically depict a clear distribution of broadly-divided particle elements (a particle size distribution pattern), although it has limited ability for minute classification of elements other than erythrocytes and leukocytes. Morphological observation of urinary erythrocytes is usually made with urinary sediment examination in Japan. However, there is a major flaw in this examination, which employs microscopic observation of urinary sediment acquired by urine centrifugation, due to cellular element destruction caused by centrifugation, supernatant residual erythrocytes and apparent low measurement values in the hypotonic urine. In contrast, the cytometry-based urinary formed-element analyzer, which analyzes non-centrifuged urine, is superior in quantitative performance. Moreover, it presumably can distinguish dysmorphic RBCs in a glomerular hematuria specimen, which often has variously-formed erythrocytes (humped doughnut- and target-shaped, for example) because these dysmorphic RBCs often fall on the smaller size side of the particle size distribution due to their tiny volume resulting from hemoglobin loss. Nevertheless, this analyzer does not always clearly distinguish urine specimens due to too few urinary erythrocytes, properties such as high acidity or hypotonicity, or their composite components.