Urine tests

Japanese: 尿検査

(1) Urine tests Urine abnormalities can be broadly divided into quantitative and qualitative abnormalities. The average urine volume in a healthy adult is 500-1500 mL per day; less than 50-100 mL is called anuria, less than 400 mL is called oliguria, and more than 2500 mL is called polyuria. Qualitative abnormalities in urine are discussed below.
a. Color and turbidity Normally, urine is pale yellow to yellowish brown, but color can change depending on the disease (Table 11-1-14), which can be a clue for differentiation. The effects of medication (e.g., deep yellow with vitamin _B2 ) must also be taken into consideration. If the urine is cloudy, hematuria, pyuria, bacteriuria, salt precipitation, etc. must be considered, and the urinary sediment must be examined to differentiate the condition.
b. Urine specific gravity and urine osmolality Urine specific gravity is an index of the kidney's concentrating and diluting power, and represents renal tubular function. It is classified as diluted urine, isotonic urine, or concentrated urine; in isotonic urine, the specific gravity is approximately 1.010 and the osmolality is approximately 290 mOsm/kg. It should be noted that compared to urine osmolality, which reflects the number of moles of solutes contained in the urine, urine specific gravity will be higher when the urine contains substances with larger molecular weights than electrolytes, such as proteins, sugars, and contrast agents.
c. Glucose in urine Almost all of the glucose filtered through the glomerulus is reabsorbed by the renal tubules. However, when blood glucose levels reach 170-180 mg/dL or higher, the reabsorption threshold is exceeded and glucose in urine appears. In addition, glucose in urine appears due to impaired reabsorption in proximal tubules.
D. Bilirubin,
Urobilinogen is used to screen for liver disease (Table 11-1-15). Normal values are bilirubin (-) and urobilinogen (±).
e. Urinary protein Urinary protein testing is the most important test for diagnosing kidney disease. Proteinuria refers to the excretion of more than 150 mg/day of protein in the urine. Even healthy people excrete small amounts of protein, but most of it is Tamm-Horsfall protein or globulin, and albumin is less than 30 mg/day. Physiological proteinuria is caused by fever or extreme exercise. To diagnose orthostatic proteinuria, urinary protein is quantified in early morning urine and urine at the time of admission. Pathological proteinuria is divided into prerenal, glomerular, tubular, and postrenal based on its mechanism (Figure 11-1-14). Prerenal proteinuria occurs when a large amount of low molecular weight proteins, such as Bence Jones protein produced in multiple myeloma, are produced, causing proteins filtered through the glomerulus to exceed the reabsorption threshold in the renal tubules and be excreted in the urine. Glomerular proteinuria is caused by leakage from the glomerulus, mainly albumin, but IgG also leaks when glomerular basement membrane damage becomes severe. The ratio of transferrin to IgG clearance (C _transferin /C _Ig _G ) is called the selectivity index, and a value of 0.2 or less is normal (high selectivity). Low molecular weight proteins such as β ₂ -microglobulin (β ₂ -MG) are mostly reabsorbed by the proximal tubule after filtering through the glomerulus, but if proximal tubular damage is present, urinary protein appears due to decreased reabsorption. In addition, N-acetyl-β-glucosaminidase (NAG), which is present in the proximal tubule, appears in the urine in association with tubular damage. Postrenal proteinuria is caused by secretion and leakage from the urinary tract.
i) Qualitative urine tests Test strips are widely used for screening purposes such as health checkups and for general patients, but their characteristics must be understood in order to make a diagnosis. Test strips are highly sensitive and specific to albumin, but have low detection rates for IgG and Bence Jones proteins. If the test strip shows a ± but the urinary protein quantification result shows 2+, the presence of Bence Jones proteins should be suspected and the protein should be identified using urine immunoelectrophoresis. In addition, the test strip method makes use of the protein error of the indicator for detection, so it will give false positives with alkaline urine. With the test strip method, urinary protein (+) is roughly standardized to 30 mg/dL and (2+) to 100 mg/dL.
ii) Quantitative urine protein Ascertaining the daily amount of urinary protein excretion is important not only for determining the prognosis of glomerulonephritis and diabetic nephropathy, but also for considering the risk of cardiovascular disease, and a new severity classification for chronic kidney disease patients based on GFR and proteinuria has been announced (see [⇨Table 11-2-1] for the new severity classification). The concentration of urinary protein changes depending on the dilution and concentration at the time of collection, so the daily amount of urinary protein cannot be estimated based on the protein concentration of a random urine sample alone. It is preferable to obtain an understanding from a 24-hour urine collection, but if urine collection is difficult in outpatient care, a urinary protein creatinine correction is used. The daily creatinine excretion in adults is about 1 g, so the daily urinary protein excretion can be estimated by correcting the protein concentration of a random urine sample for creatinine. For example, if the protein concentration in a random urine sample is 250 mg/dL and the creatinine concentration is 100 mg/dL, then 250/100 = 2.5 g/g Cr, and the urinary protein content can be estimated to be 2.5 g/day.
iii) Microalbuminuria Albumin excreted in urine in excess of the normal range is called microalbuminuria. Albumin excretion in urine varies throughout the day, being low at night and increasing with exercise, so it is preferable to collect random urine in the morning. Microalbuminuria is defined as a urinary albumin value of 30-299 g/g Cr in random urine, 30-299 mg/day in 24-hour urine collection, and 20-199 μg/min in overnight urine collection. Microalbuminuria is often used to diagnose early diabetic nephropathy, but it has recently become important as a marker of vascular endothelial injury and a risk factor for cardiovascular disease. Proteinuria can be converted to albuminuria by multiplying by approximately 0.6. However, at the stage of microalbuminuria, the proportion of renal tubular protein is high, so 150 mg of proteinuria is equivalent to 30 mg of albuminuria.
iv) The tubular proteins _α1 -microglobulin and _β2 -MG are both low molecular weight proteins that are filtered in the glomerulus and reabsorbed in the proximal tubule, and their increased excretion raises the possibility of tubular damage. However, when serum _β2 -MG levels increase in response to inflammation, such as in malignant tumors or collagen disease, urinary _β2 -MG levels also increase. Furthermore, urinary excretion of NAG, an enzyme derived from tubular lysosomes, and γ-GTP derived from the tubular brush border also increases due to tubular damage.
f. Urinary occult blood/hematuria Hematuria is the presence of red blood cells in urine; when 1-2 mL of blood is present in 1 L of urine, it turns cola-colored and is called macroscopic hematuria. On the other hand, the urine occult blood test detects the oxidation-reduction reaction of hemoglobin, so in addition to hematuria, it will also test positive for hemoglobinuria due to hemolysis and myoglobinuria due to rhabdomyolysis. These can be differentiated by microscopic examination of the urinary sediment (Table 11-1-16). Urinary occult blood (1+) corresponds to a hemoglobin concentration of 0.06 mg/dL, 20 red blood cells/μL, and 5 red blood cells/HPF in the urine sediment, and is called microscopic hematuria.
g. Urinary sediment i) 5 or more red blood cells/HPF is pathological. They are confetti-like at high osmolarity and low pH, and spherical at low osmolarity and high pH. In glomerular hematuria, red blood cells show a variety of shapes in the same specimen due to changes in osmolarity when passing through the lumen of the renal tubule, but in lower urinary tract bleeding (non-glomerular), they show a uniform shape. ii) 1 or more white blood cells/HPF is pathological. This suggests inflammation of the urinary tract, particularly urinary tract infection, but they also appear in interstitial nephritis, acute glomerulonephritis, lupus nephritis, etc. iii) Casts These casts are made primarily of Tamm-Horsfall protein secreted from the ascending limb of Henle, and are molded on the lumen of the renal tubule. Hyaline casts without internal inclusion bodies can also appear due to dehydration, fever, etc., and on their own have no pathological significance; however, red blood cell casts, granular casts, and waxy casts that appear to contain cellular components should be considered as indications of renal parenchymal damage.
Epithelial casts contain renal tubular epithelial cells and often appear in cases of kidney and tubular injury such as acute tubular necrosis and glomerulonephritis, while the components of granular casts are mostly transformed renal tubular epithelial cells and often appear in cases of renal parenchymal injury such as chronic glomerulonephritis and renal failure. Erythrocyte casts appear when glomerular hematuria is present in conditions such as acute glomerulonephritis and IgA nephropathy, leukocyte casts appear when infection or inflammatory disease is present such as pyelonephritis, interstitial nephritis, and lupus nephritis, and fatty casts appear at a high rate in cases of nephrotic syndrome. Waxy casts indicate long-term obstruction of the renal tubule lumen and are often found in cases of severe kidney disease such as nephrotic syndrome, renal failure, and end-stage nephritis. [Inosaka Yoshitaka]

Table 11-1-14
Urine color and diseases

Table 11-1-14

Table 11-1-15
Urinary bilirubin and urobilinogen ">

Table 11-1-15

Table 11-1-16
Differential diagnosis of urinary occult blood test

Table 11-1-16

Figure 11-1-14
Differential diagnosis of urinary occult blood test

Figure 11-1-14

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

（1）尿検査
　尿の異常は，量的な異常と質的な異常に大別できる．尿量は，健常成人では1日500〜1500 mLであり，50〜100 mL以下を無尿，400 mL以下を乏尿，2500 mL以上を多尿とよぶ．以下尿の質的異常について述べる．
a.色調，混濁
　通常，尿は淡黄色から黄褐色を呈するが，疾患により色調の変化をきたすことがあり（表11-1-14），鑑別の手がかりとなる．なお，薬剤の影響（ビタミンB₂で濃黄色など）も考慮する．尿が混濁している場合は，血尿，膿尿，細菌尿，塩類の析出などを考慮し，尿沈渣にて鑑別する．
b.尿比重・尿浸透圧
　尿比重は，腎の濃縮力・希釈力の指標であり，尿細管機能を表す．希釈尿･等張尿・濃縮尿に分類され，等張尿では，比重は1.010程度，浸透圧は290 mOsm/kg程度である．尿に含まれる溶質のモル数を反映する尿浸透圧に比べ，尿比重は，蛋白質・糖・造影剤のように電解質より分子量の大きい物質が尿に含まれていると高値を示すことに注意する．
c.尿糖
　糸球体で濾過されたグルコースは尿細管でほとんどすべて再吸収される．しかし血糖値が170～180 mg/dL以上になると，再吸収の閾値をこえて尿糖が出現する．また，近位尿細管障害でも，再吸収障害により尿糖が出現する．
d.ビリルビン，
ウロビリノーゲン
　肝疾患のスクリーニングに用いられる（表11-1-15）．正常ではビリルビン（−），ウロビリノーゲン（±）である．
e.尿蛋白
　尿蛋白検査は，腎疾患の診断において最も重要な検査である．蛋白尿は，150 mg/日以上の蛋白が尿中に排泄されることを指す．健常人でも蛋白は少量排泄されているが，多くはTamm-Horsfall蛋白やグロブリンであり，アルブミンは30 mg/日未満である．生理的蛋白尿として，発熱・過激な運動などがある．起立性蛋白尿の診断のためには，早朝尿と来院時尿の尿蛋白定量を行う．病的な蛋白尿はその機序から，腎前性，糸球体性，尿細管性，腎後性に分けられる（図11-1-14）．腎前性蛋白尿は，多発性骨髄腫で産生されるBence Jones蛋白のように低分子蛋白が大量に産生されるために，糸球体を濾過した蛋白が尿細管での再吸収閾値を超えて尿中に排泄されるものである．糸球体性蛋白尿は，糸球体からの漏出によるものであり，アルブミンがその主体であるが，糸球体基底膜障害が高度になると，IgGも漏出する．トランスフェリンとIgGのクリアランスの比（C_transferin/C_Ig_G）をselectivity indexといい，0.2以下が正常（高選択性）である．β₂-ミクログロブリン（β₂-MG）のような低分子蛋白は糸球体を濾過した後，近位尿細管でほとんど再吸収されるが，近位尿細管障害が存在すると，再吸収低下により尿蛋白が出現する．また，近位尿細管に存在するN-acetyl-β-glucosaminidase（NAG）は，尿細管障害に伴って尿中に出現する．腎後性蛋白尿は，尿路からの分泌・漏出によるものである．
　ⅰ）尿定性試験
　試験紙法は，健診などのスクリーニングから一般患者まで広く用いられているが，診断のためには，その特性を知る必要がある．試験紙法は，アルブミンには感度・特異度が高いが，IgGやBence Jones蛋白などには検出度が低い．試験紙法で（±）だが，尿蛋白定量で（2＋）というような乖離がみられる場合は，Bence Jones蛋白などの存在を疑い，尿免疫電気泳動法を用いて蛋白の同定を行う．また，試験紙法は，指示薬の蛋白誤差を利用して検出しているため，アルカリ尿で偽陽性を示す．試験紙法では，尿蛋白（＋）が30 mg/dL，（2＋）が100 mg/dLにほぼ統一されている．
　ⅱ）尿蛋白定量
　糸球体腎炎や糖尿病性腎症の予後の判定のみならず，心血管病のリスクを考える上で，1日の尿蛋白排泄量を把握することが重要であり，GFRと蛋白尿による慢性腎臓病患者の新しい重症度分類が発表された（新しい重症度分類については【⇨表11-2-1】）．尿蛋白は，採取時の希釈・濃縮により濃度が変化するので，随時尿の蛋白濃度だけでは，1日尿蛋白量を推定することはできない．24時間蓄尿での把握が望ましいが，外来診療で蓄尿が困難な場合は，尿蛋白クレアチニン補正を用いる．成人の1日のクレアチニン排泄量は1 g程度であるので，随時尿の蛋白濃度をクレアチニンで補正することにより1日尿蛋白排泄量を推定することができる．たとえば，随時尿の蛋白濃度が250 mg/dLで，クレアチニン濃度が100 mg/dLの場合，250/100＝2.5 g/g Crとなり，尿蛋白は2.5 g/日と推定できる．
　ⅲ）微量アルブミン尿
　正常範囲をこえて尿中にアルブミンが排泄されている状態を微量アルブミン尿とよぶ．日内変動があり，夜間に低く，運動により増加するため，随時尿では午前中の採取が望ましい．微量アルブミン尿は，尿中アルブミン値が随時尿で30〜299 g/g Cr，24時間蓄尿で30〜299 mg/日，夜間蓄尿で 20〜199 μg/分と定義される．微量アルブミン尿は早期糖尿病性腎症の診断によく用いられるが，最近では血管内皮傷害のマーカーとして心血管病のリスク因子としても重要である．蛋白尿をアルブミン尿に換算する場合は，ほぼ0.6倍すればよい．ただし，微量アルブミン尿の段階では，尿細管性蛋白などが占める割合が多いため，蛋白尿150 mgがアルブミン尿30 mgに相当する．
　ⅳ）尿細管性蛋白α₁-ミクログロブリン，β₂-MGはいずれも糸球体で濾過され近位尿細管で再吸収される低分子蛋白であり，これらの排泄増加は尿細管障害を疑う．ただし，悪性腫瘍や膠原病など炎症反応性に血清β₂-MGが増加した時は，尿中β₂-MGも増加する．また，尿細管のライソゾーム由来の酵素であるNAGや尿細管刷子縁由来のγ-GTPも尿細管障害により尿中排泄が増加する．
f.尿潜血・血尿
　尿中に赤血球が混入した状態を血尿といい，尿1 Lに血液が1〜2 mL混入するとコーラ色を呈し，肉眼的血尿と呼ばれる．一方，尿潜血反応はヘモグロビンの酸化還元反応を検出しているため，血尿以外に，溶血によるヘモグロビン尿や横紋筋融解症によるミオグロビン尿でも陽性となる．これらの鑑別には尿沈渣による検鏡等にて可能である（表11-1-16）．尿潜血（1＋）はヘモグロビン濃度0.06 mg/dL，赤血球20 個/μL，尿沈渣では5 個/HPFに相当し，これを顕微鏡的血尿とよぶ．
g.尿沈渣
　ⅰ）赤血球　5 個以上/HPFで病的である．高浸透圧や低pHでは金平糖状を，低浸透圧や高pHでは球状を呈する．糸球体性血尿では，尿細管腔通過時の浸透圧変化等により赤血球は同一標本で多彩な形態を示すが，下部尿路出血（非糸球体性）では均一な形態を示す．　ⅱ）白血球　1個以上/HPFで病的である．尿路の炎症，特に尿路感染症を疑うが，間質性腎炎や急性糸球体腎炎，ループス腎炎などでも出現する．　ⅲ）円柱　Henleの上行脚から分泌されるTamm-Horsfall蛋白が主成分となり尿細管腔を鋳型としたものである．内部に封入体のない硝子円柱は，脱水・発熱等でも出現し，単独では病的意義がないが，細胞成分を含んだような赤血球円柱，顆粒円柱，ろう様円柱などは腎実質性傷害の影響を考える．
　上皮円柱は，尿細管上皮細胞が封入されたもので，急性尿細管壊死，糸球体腎炎などの腎・尿細管傷害で出現することが多く，顆粒円柱の成分も，ほとんどは尿細管上皮細胞が変成したもので，慢性糸球体腎炎，腎不全などの腎実質傷害で出現することが多い．赤血球円柱は，急性糸球体腎炎，IgA腎症など糸球体性の血尿を伴うとき，白血球円柱は，腎盂腎炎，間質性腎炎，ループス腎炎など感染症や炎症性疾患を伴うとき，脂肪円柱は，ネフローゼ症候群では高率に出現する．ろう様円柱は，尿細管腔の長期閉塞を意味し，ネフローゼ症候群，腎不全，腎炎末期などの重篤な腎疾患に認めることが多い．［猪阪善隆］

表11-1-14
尿の色調と疾患">

表11-1-14

表11-1-15
尿ビリルビンとウロビリノーゲン">

表11-1-15

表11-1-16
尿潜血反応の鑑別">

表11-1-16

図11-1-14
尿潜血反応の鑑別">

図11-1-14

出典　内科学第10版内科学第10版について　情報

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