Urinalysis
AFP 2005;71:1153-62
高岸 勝繁

今 尿検査が熱い！
• 尿検査は,
– 簡便
– 安価
– そして情報量が多い
2

採尿
• 中間尿を清潔操作にて採尿するのが普通
– 女性には排尿前に陰部を拭くことが推奨されるが,
どちらにしろコンタミの確率は変わらない 32% vs 29%
(Arch Intern Med 2000;160:2537-40)
• 採尿後, 2hr以内に検査を行う
– どうしても無理ならば冷蔵保存を. (淋菌疑いは×)
– 2hr以上経過した尿検査は信用できない

尿を愛でる(肉眼所見)
• 尿の色より
混濁 リン酸塩, WBC, 乳び尿, 脂肪尿, シュウ酸尿
褐色 ビリルビン, ミオグロビン, Beets, Blackberries, Rhubarb
Fava beans, Aloe, Laxatives, Chlorpromazine,
Thioridazine, Propofol, Porphyrin(鉛, 水銀中毒)
黒褐色 ビリルビン, メラニン, メトヘモグロビン, Methyldopa
緑色, 青 緑膿菌UTI, ビリベルジン (ビリルビン), アスパラガス,
Amitriptyline, Indomethacin, Cimetidine, Promethazine
オレンジ ビリルビン, リファンピシン, Carotene(人参など)
ビタミンB, Warfarin, Rifampin, Pyridium, Urochrome(脱水)
赤色 血尿, ヘモグロビン, ミオグロビン, ポルフィリア
黄色 濃縮尿

5

• Purple urine bag syndrome
– バルーン留置患者における,
慢性便秘 + UTIでおこる現象.
– 便秘により腸内細菌が増殖し,
トリプトファンがインジカンへ
分解され, 尿中へ排泄.
– 尿中の細菌により,
インジカン → インジゴとなり,
バック内で紫色になる.
6

• 尿の香り
– 通常の尿の臭い “Urinoid”と表現, 濃縮尿で強くなる(Not 感染)
– 感染 刺激臭, DKA Fruity, sweet
消化管-膀胱瘻 便臭, シスチン 硫酸臭,
– 長期間膀胱内に貯留した尿はアルカリ発酵が進み, アンモニア臭↑

Dipstick Urinalysis
• 簡易だが, 偽陽性, 偽陰性は少ない
• 偽陽性, 偽陰性の起こる原因
Dipstic test 偽陽性 偽陰性
Bill Phenazopyridine Chlorpromazine, Selenium
運動, 脱水, 月経, Captopril, SG↑, pH < 5.1
Blood
ヘモグロビン尿, ミオグロビン尿 タンパク尿, Vit C
Glu ケトン, レボドパ SG↑, UA, Vit C
酸性尿, SG↑, meana,
Ketone 採尿∼検査の遅れ
Phenolphthalein, 薬剤代謝物
SG↑, 尿糖, ケトン尿, タンパク尿
Leuko コンタミ
Cephalexin, Tetracycline, AG, Vit C
コンタミ, 空気中のNを検出 SG↑, Urobilinoggen↑, pH < 6.0
亜硝酸塩
Phenazopyridine Nitrate reductase(-) Bacteria, Vit C
アルカリ, 濃縮尿, アンモニア尿
Protein 酸性尿, 希釈尿, アルブミンではない
Phenazopyridine
SG デキストラン, 造影剤, 蛋白尿 アルカリ尿
Urobilinogen Nitrite↑, Phenazopyridine

尿比重
• Specific Gravity(SG)
• 尿比重 下2桁 ＝ 0.03 x 尿浸透圧 + 0.38 (r=0.94)
• 尿比重 1.002 ＝ 尿浸透圧50mOsm/L が下限
– 尿比重 1.010 ≒ 尿浸透圧300mOsm/L ≒ 等浸透圧
常に尿比重1.010付近ならば, 希釈・濃縮障害がある
常に尿比重 1.009-1.011ならば, 透析寸前
– 尿比重は通常1.015-1.025, 昼間に1.020あれば濃縮尿を疑う
• 通常500-800mOsm/L, 希釈尿=< 200mOsm/L, 濃縮尿 >=850
• 尿比重1.040 = 尿浸透圧1300mOsm/Lが上限
– 高齢者では, 900mOsm/L = 尿比重1.027が限界
• 尿比重1.030-1.050 で, 浸透圧が300mOsm/Lと解離
– 大量の尿糖, ネフローゼ, 造影剤, カルベニシリン, マンニトールなど

pH
• 尿pH
– 正常値; 4.5-8, 通常 やや酸性(5.5-6.5)
– 通常, 血液pHを反映する(RTAは例外)
夜間の絶食 + 酸性物質DIVでも pH<5.5を達成できない RTA
– タンパクの摂取, 酸性フルーツ(クランベリー)の摂取にて酸性化
クエン酸の摂取にてアルカリ化
– UTIでのアルカリ尿は, 尿素分解細菌の感染を示唆.
その際, Mg, アンモニア リン酸塩を伴うこともある
(尿酸結石は酸性尿にて析出)
– 代謝性アルカローシスにも関わらず, pH6.0以下であれば,
HCO3再吸収の亢進 脱水を示唆する

血尿
• 肉眼的血尿; 1Lの尿に1mlの血液が混入すれば肉眼的血尿.
• 顕微鏡的血尿; 1-10/HPFを満たすもの.
– 顕微鏡的血尿は一般人口の0.19-16.1%で認められ,
男性<女性であることが多い.
– 成人のPrimary Care Settingに限定すると, 2.5-4.3%
– 一過性の顕微鏡的血尿ならば6-39%
3回以上の検査が陽性となる持続的血尿ならば頻度は0.5-2.0%.
Prim Care Clin Office Pract 2010;37:461-72
• 腫瘍のリスクが高いのは肉眼的血尿
– 再発性の顕微鏡的血尿における腫瘍のリスクは∼8.9%だが,
肉眼的血尿では10-28%.
AJR 2012; 198:1256–1265
11

aIncludes 10 cases of prostate carcinoma.
Dutch Guidelines on Hematuria
bAnalysis of patients with CT urography: persistent microscopic hematuria after initial negative analysis.
AJR 2012; 198:1256–1265
Ultrasound sufficiently accurate for diagnosis in hematu- diagnosis [43], the European Urological
Ultrasound is suitable as first-line diag- ria, improved compared with excretory urog- in Malignancy Association (EAU) guideline lags behind,
Malignancy in
nostic test, Type,
Study
especially in young patients with Patients With combination is inferiorWomen ≤ 40 Years the Men ≤ 40 Years still recommends ex-
Patients With
raphy. The Malignancy
to unen- and 2009 version
Reference Hematuria Microhematuria Urolithiasis (%) Old (%) Old (%) Pathology (%)
nonurologic diseases. A large study showed hanced CT for stone disease but does not cretory urography for stone diagnosis [44].
aProspective
high specificity but moderate sensitivity miss significant disease. Studies found sensi- For hematuria, multiple studies have now
for the diagnosis of bladder tumors [35]. In tivities of 77–79%,8.9a 12a
Boman et al. [12] 581 247 0 (≤ 50) 0 (≤ 50) 43
with negative predictive shown the superiority of CT urography over
comparison with excretory urography, ultra- 1950 of 46–68% [40, 41]. With modern 1.1
Edwards et al. [13] 4020 values 4.8 NA ul- excretory urography. There is also a low
0.7 13
sound showed a higher sensitivity for bladder trasound techniques, such as tissue harmon- sensitivity (< 60%) for renal tumors small-
Sultana et al. [14] 614 381 5 4.7 0 (≤ 50) 0 NA
tumors and equal (i.e., moderate) sensitivity ic imaging, sensitivity for the combination er than 3 cm for excretory urography [45].
for upper urinary tract tumors [36, 37]. Ul- 1034 be improved [42]. The role of contrast-
Murakami et al. [15] 1034 can 2.9 NA 0 0 54
trasound et al. [16] not sensitive (19–32%) for enhanced ultrasound5.4 not yet well defined.
Khadra alone is 1930 982 is 4 0 CT Urography 1.7 32
stone detectionb[38, 39], but its600
Lang et al. [17] sensitivity for 600 7.3 0 NA CT urography provides detailed informa-
NA 43
combined stone detection and pyelocalyceal Excretory Urography tion on the urinary tract. The problem in in-
Jaffe et al. [18] 372 75 after 3 mos 3 8 NA NA 43
dilatation is much better. Excretory urography has long been the terpretation of the results is variability in the
Retrospective cornerstone for evaluation of the upper uri- definitions of what CT urography actually en-
Combined Radiograph and Ultrasound
El-Galley et al. [19] 404 nary tract. However, 3 6 though metaanal-stones) and, therefore, the CTU Working Group
140 even 0 (total 8% tails, 0 NA
Hovius the 1980s, it has been1509
Since et al. [20] known that the yses show the highest positive and negative of the European Society of Urogenital Radiol-
443 5 0 NA NA 24
combination of radiograph and ultrasound is likelihood ratio of unenhanced CT for stone ogy has tried to suggest a definition as follows:
Note—NA = not applicable.
aIncludes 10 cases of prostate carcinoma.
TABLE of patients withon urography: persistent microscopic hematuria after initial negative analysis.
bAnalysis
5: Studies CT the Incidence of Malignancy in Macroscopic Visible Hematuria
Study Type, Patients With Patients With Malignancy Malignancy in Patients Malignancy in Patients
Reference
Ultrasound Hematuria Macrohematuria accurate for diagnosis in hematu- Old
sufficiently Urolithiasis (%) ≤ 40 Years diagnosis [43], Years Old
> 40 the European Urological
Pathology (%)
Prospective is suitable as first-line diag-
Ultrasound ria, improved compared with excretory urog- Association (EAU) guideline lags behind,
nostic test, al. [12]
Boman et
especially in young patients with
581
raphy. The combination is inferior to unen- and the NA version still recommends ex-
211 24a 5.4a NA
2009 79
nonurologic diseases. A large study showed hanced CT for stone disease but does not cretory urography for stone diagnosis [44].
Edwards et al. [13] 4020 2071
a high specificity but moderate sensitivity miss significant disease.0Studies foundmen; 1% women hematuria, multiple studies have now
19 6.7%
sensi- For NA 27
forSultana et al. [14] of bladder tumors [35]. In
the diagnosis 614 233
tivities of 77–79%, 28 0 negative10% (≤ 50 years old)
with predictive shown the superiority old)CT urography over
35% (≥ 50 years of 35
comparisonal. [16] excretory urography, ultra-
Khadra et with 1930 948 24 0 modern ul- excretory urography. There is also47a low
values of 46–68% [40,≠41]. With 0.8% men; 0% women 21% men; 16% women
sound showed a higher sensitivity for bladder
Mishriki et al. [21] 578
trasound techniques, such as tissue harmon- sensitivity (< 60%) for renal tumors small-
578 19.5b ≠ 0 NA NA 36
tumors and equal (i.e., moderate) sensitivity ic imaging, sensitivity for the combination er than 3 cm for excretory urography [45].
Retrospective
for upper urinary tract tumors [36, 37]. Ul- can be improved [42]. The role of contrast-
trasound alone [19]not sensitive (19–32%) for
El-Galley et al. is 404 264
enhanced ultrasound is 12 yet well defined.
10 ≠ not NA NA
CT Urography NA
stone detection [38, 39], but its sensitivity for
Hovius et al. [20] 1509 1032 23 ≠ 0 NA CT urography provides detailed informa-
NA 60
combined stone detection and pyelocalyceal
Note—NA = not applicable.
Excretory Urography tion on the urinary tract. The problem in in-
dilatation18 cases ofbetter. carcinoma.
aIncludes is much prostate Excretory urography has long been the terpretation of the results is variability in the
b

• 試験紙法と尿沈渣の関係
試験紙 (-) (±) (+) (++) (+++)
尿沈渣 0.03mg/dL 0.03mg/dL 0.06-0.10mg/dL 0.20-0.50mg/dL >1.00mg/dL
0-1/HF 1653(58.9%) 155(19.1%) 18(3.4%) 14(1.6%) 2(0.5%)
1-4/HF 1131(40.3%) 425(52.3%) 54(10.3%) 18(2.1%) 7(1.8%)
5-9/HF 19(0.7%) 194(23.9%) 301(57.2%) 30(3.5%) 11(2.89%)
10-19/HF 2(0.07%) 32(3.9%) 115(21.9%) 177(20.7%) 17(4.5%)
20-29/HF 1(0.04%) 2(0.25%) 19(3.6%) 62(7.2%) 21(5.5%)
30-49/HF 0(0%) 4(0.5%) 18(3.4%) 500(58.3%) 39(10.3%)
50-100/HF 0(0%) 1(0.1%) 1(0.2%) 44(5.1%) 69(18.1%)
>100/HF 0(0%) 0(0%) 0(0%) 12(1.4%) 214(56.3%)
• (±),(+)は1桁, (++)は2桁, (+++)は3桁と覚える！
上田ノートより

• 血尿は健常男性の2.6%, 女性の8.1%で認める
– 21000名の尿のDipstick test (Clin Chem 1987;33:2106-8)
– 若年女性では月経による血尿偽陽性,
高齢女性では尿路感染による血尿陽性が多いと考えられる
• 血尿の原因 Age 男性 女性
(JAMA 1990;263:2475-80)
タンパク尿 血尿 タンパク尿 血尿
原因疾患 肉眼的 顕微鏡的
20-29yr 5.5% 1.6* 1.2% 1.3* 7.7% 5.6* 9.7% 11.1*
腎細胞癌 3.6% 0.5%
30-39yr 4.2% 2.7* 2.4% 2.3* 4.8% 2.6* 10.9% 9.9*
前立腺癌 2.4% 0.5%
40-49yr 4.7% 3.0* 3.0% 3.1* 3.7% 2.8* 12.2% 15.0*
尿管癌 0.8% 0.2% 50-59yr 5.2% 4.0* 3.0% 3.8* 2.1% 2.9* 5.3% 12.4*
膀胱癌 15% 4% 60-69yr 5.4% 6.5* 2.9% 4.5* 3.1% 3.6* 4.5% 11.3*
尿路感染症 33% 4.3% 70-74yr 7.7% 9.9* 5.8% 4.6* ― 5.1* 17.4% 17.7*
尿路結石 11% 5% 計 4.9% 3.7* 2.6% 3.4* 3.9% 3.0* 8.1% 12.9*
前立腺肥大 13% 13%
* Internal Med 1995;34:475-80; 日本国内26082名の解析
糸球体腎炎 0% 2.2%
出血傾向 1% 0%
不明 8.4% 43%
血尿の4大原因
悪性腫瘍, 尿路結石, 尿路感染, 糸球体腎炎

血尿を見たら？
Primary Care Settingでのアプローチ
Visible Haematuria Non-Visible Haematuria
eGFRをCheck
一過性を除外, UTIを除外
一過性, UTIを除外
無症候性
症候性 中止
正常値 dipstick 2/3で陽性*
ACR; 血圧, eGFR, ACR, PCR評価*
Alb/Cr <30
PCR; >=40yr <40yr
Prot/Cr <50
異常なし 異常あり
eGFR >=60ml/mim
BP < 140/90 泌尿器系評価 腎臓評価
原因不明
*2-3wkの間に評価.
Primary care monitoring**
BMJ 2009;338:a3021

• Primary Care monitoring
– BP, eGFR, ACR/PCRを年1回評価
– 肉眼的血尿, 症候性血尿を認めた場合(ACR>30, PCR>50)
泌尿器科コンサルト
– 蛋白尿増悪, eGFR<30, eGFR低下(5ml/yr, 10ml/5yr)ならば,
腎臓内科コンサルトをする
– GFRは2回以上評価すること.
BMJ 2009;338:a3021

(a)
Low-risk patients
Age < 40 years
(b) AUAのガイドラインより
No smoking history
No history of chemical exposure 成人例の血尿の精査
No irritative voiding symptoms
No history of gross hematuria Curr Opin Obstet Gynecol 2012, 24:324–330
No previous urologic history
Upper tract imaging
Cytology Cystoscopy
Positive, Positive
atypical or High-risk patients
suspicious
Treat
Cystoscopy Complete evaluation
(upper tract imaging
cytology,cystoscopy)
Positive
Negative
Treat Positive
Negative
UA, BP, Treat
Consider cytology
UA, BP, 6, 12, 24 & 36
cytology months
6, 12, 24 & 36
months
Negative for 3 years Gross hematuria, Negative for 3 years Persistent hematuria, Gross hematuria,
Persistant hematuria, abnormal cytology, HTN, proteinuria, abnormal cytology,
HTN, proteinuria, irritative voiding glomerular bleeding irritative voiding
glomerular bleeding symptoms without symptoms without
infection infection
No further urologic Evaluate for primary
No further urologic Evaluate for primary Repeat complete Repeat complete
monitoring renal disease
monitoring renal disease evaluation evaluation
Glomerular bleeding or “Isolated hematuria”
Glomerular bleeding or “Isolated hematuria”
proteinuria
proteinuria
Renal biopsy Biopsy controversial Renal biopsy Biopsy controversial

• 上部尿路の画像検索方法 Med Clin N Am 95 (2011) 153–159
画像検査 限界
IV urography 腎臓実質の病変の精査には向かない. 造影剤IVが必要
逆行性腎盂造影 腎臓実質の病変の精査には向かない. 侵襲性が高い
超音波検査 尿路結石評価, <3cmの腎腫瘍, 尿路奇形評価には向かない
MRI 高価. 時間がかかる. 腎結石への感度は低い
CT urography 高価. Radiation doseが最も多い
– どの検査を用いるべきかは規定されていないがCTUが選択される事が多い.
CTUは単純CT, 造影(腎実質phase, Late phase)の3層で評価する.
– IV urographyによる尿管, 膀胱腫瘍の検出能は,
2cmのMassで21%, 2-3cmで52%, >3cmで85%となる.
AJR 2010; 195:W263–W267

• 尿細胞診
– 高分化型癌への感度, 特異度は良好だが,
低分化型癌の場合は感度45-70%と不良.
– 従って, 尿中癌マーカー(BTA stat, NMP-22, UroVysion)など開発されたが,
どれも臨床で推奨されるほど確立されていないのが問題.
Med Clin N Am 95 (2011) 153–159
19

raphy [52–54], with relatively the lowest de- ity for better tissue characterization than oth- In contrast, CT urography is associated
tection rate in the ureter. CT urography also er imaging techniques do. However, MRU is with much higher doses. Even when opti-
performs well in the lower urinary tract and, costly, technically demanding, and not wide- mized in average-sized patients, a pilot study
• リスク別の血尿の評価方法の推奨 (悪性腫瘍評価)
in selected cases, can obviate flexible diag- ly practiced. Therefore, MRU expertise is showed that CT urography delivered an aver-
nostic cystoscopy so that patients may pro- available only in specific dedicated centers. age dose of 16 mSv for two phase CT urogra-
ceed directly to rigid therapeutic cystoscopy MRU is usually performed as a combina- phy protocols and 22 mSv for three phase CT
[55–57]. Although it has not been formally tion of static fluid T2-weighted and dynam- urography (van der Molen AJ, presented at the
TABLE 6: Summary of a Risk-Based Approach to Imaging of Hematuria AJR 2012; 198:1256–1265
Risk of Malignancy
Characteristics Low Medium High
Type of hematuria Microhematuria Microhematuria Macrohematuria Macrohematuria
Age (y) ≤ 50 > 50 ≤ 50 > 50
First line (Ultrasound) or (cystoscopy) Ultrasound or cystoscopy Ultrasound or cystoscopy CT urography or cystoscopy
Second line If first line negative, stop If first line negative and risk or If first line negative and risk or If first line negative and persisting
persisting hematuria, CT persisting hematuria, CT hematuria, urine cytology
urography urography
Third Line If second line negative and risk If second line negative and risk If second line positive, retrograde
or persisting hematuria, urine or persisting hematuria, urine ureteropyelography or
cytology cytology ureterorenoscopy
Fourth Line If third line positive, retrograde If third line positive, retrograde
ureteropyelography or ureteropyelography or
ureterorenoscopy ureterorenoscopy
Note—See Appendix for additional details.
1260 AJR:198, June 2012
20

• Hematuriaの出血部位
– 潜血, RBC, 変形RBC, RBC Castにて判別
– 糸球体性血尿; 大半がタンパク尿を伴う(>=500mg/d). RBC Cast (+)
腎生検で糸球体腎炎と診断された20%が血尿のみ
– 腎性血尿; 糸球体性と同様, 大半がタンパク尿を伴う.
RBC Cast(-), 変形RBC(-)
– 尿路由来; 悪性腫瘍, 結石, 感染症で多い
タンパク尿(-), RBC Cast(-), 変形RBC(-)
著しい血尿の20%で悪性腫瘍が見つかる
無症候, 顕微鏡的血尿の5-22%で重大な泌尿器系疾患(+)

• 糸球体性の血尿
– 有棘赤血球 >=5%で Sn 52%[44-61], Sp 98%[94-99]
LR(+) 25[9.2-66], LR(-) 0.5[0.4-0.6]で糸球体性を示唆
(Kidney Int 1991;40:115-20)
– 凝血塊の存在は,
糸球体性の可能性を下げる
– 糸球体性の血尿単独で
腎機能低下(-)ならば, IgA腎症.
経過観察でOKだが,
蛋白尿(+)の場合は生検が必要である
• 顕微鏡によるRBC評価は迅速に
– 5hrで5-9%, 24hrで11-28%, 72hrで29-35%低下する.
(Clin Chem Lab Med 2008;46:703-13)

尿路悪性腫瘍の血尿
• 尿路悪性腫瘍のRisk Factor
– 男性, 喫煙者, 鎮痛薬(フェナセチン)長期使用
染料暴露, シクロホスファミド使用
– 50-60歳男性の無症候性間欠的血尿での悪性腫瘍頻度は8-9%
間欠的血尿でも可能性は高い (J Urol 1992;148:289-92)
• 悪性腫瘍の検査
– 尿細胞診, 尿中NMP-22(尿中核マトリクス蛋白22)簡便, 低侵襲
細胞診は感度が低いため, 3回は提出する必要あり
Test (JAMA 2005;293:810-6) Sn(%) Sp(%) LR(+) LR(-) NMP-22は細胞診よりも
細胞診 16[9-26] 99[99-100] 19.8 0.8 感度高く, 特異度が低い
NMP-22 >=10U/mL 56[44-67] 86[84-88] 3.9 0.5 SRL.ではCutoff >=12U/mL
– 他, US, CT, PSA, 排泄性腎盂造影など画像検査を考慮
– 異常あれば膀胱鏡, 腎生検, 前立腺生検を考慮
– 全て正常でも3年はフォロー必要;
3年以内に1%の悪性疾患が見つかる(J Urol 1990;144:99-101)

タンパク尿
• Proteinuria
– 健常男性の4.9%, 女性の3.9%でタンパク尿を認める
(Clin Chem 1987;33:2106-8)
– 糸球体は通常 < 20000Daltonのタンパクを通過させる
その後近位尿細管にて再吸収・代謝される
– > 150mg/day (10-20mg/dL)をタンパク尿と定義
– Microalbuminuria 30-150mg/day, 早期腎障害を示唆(DM)
– Dipstick test; Bence Jones, γ-globulinは検出不可
Alb尿に関してはSN/SP 99/99%
蛋白定性 ± + ++ +++ ++++
濃度 10-15mg/dL 30mg/dL 100mg/dL 300mg/dL 1000mg/dL
– タンパク尿は “Transient” “Persistent” で分類される
• Transient 糸球体血流の一過性の変化に由来するもの
> 起立性タンパク尿, CHF, 脱水, ストレス
発熱, 痙攣など
• Persistent Glomerular, Tubular, Overflowの3種類

タンパク尿
• Glomerular; 糸球体の異常 Alb尿が多い
– FGS, MPGN, MGN, Minimal change, Primary
IgA腎症(Berger’s), IgM 腎症
– Alport’s, Amyloidosis, SLE, DM, Fabry’s
薬剤性(NSAID, Gold, ACEIなど) Secondary
感染症(HIV, 梅毒, 肝炎, Post-streptococcal infection)
悪性腫瘍, サルコイドーシス, 鎌状赤血球症
• Tubular; 尿細管上皮障害 濾過タンパクの再吸収, 代謝×
Low-molecular-weight proteinがメイン, 通常2g/dayを超えない
– アミノ酸尿, 薬剤(NSAID, 抗生剤), Fanconi’s
重金属, 高血圧性腎症, 間質性腎炎
• Overflow; Low-molecular-weight protein が
尿細管の再吸収能を上回るほど濾過される
– Hemoglobinuria, Multiple Myeloma, Myoglobinuria

タンパク尿は何故悪いのか？
• 低Alb血症, 電解質バランスを崩す
• GFRを低下させ続ける
– 低選択性蛋白尿にて補体の活性化,
複合体が糸球体、尿細管上皮の障害に寄与する
MDRD(n=585, GFR平均値 39mL/min)
尿蛋白 (g/day) <1.0 1-3 >3.0
GFR減少値
1.7±0.3 4.9±0.5 8.3±0.7
(mL/min/yr/1.73m2)
REIN(n=352, GFR平均値 44mL/min)
尿蛋白 (g/day) <2.0 2-3 3-4.5 >4.5
GFR減少値
2.5±0.04 4.6±0.1 6.5±0.1 9.5±0.2
(mL/min/yr/1.73m2)

Spot尿 P/C Ratio(PCR)
• 24hr蓄尿は難しい
– 朝排尿し, それから蓄尿. 翌朝、24hr後の排尿で終了
– 尿カテ管理されていない状況では結構困難.
全体の12-15%が24hr尿として認められない (AJKD 2006;47:1-7)
• Spot尿にてフォローする方法
– Protein/Creatinine ratioにて評価
– P/C ratio = 24hr尿中タンパクの総量(g/dL)
– <1.7: 12ヶ月フォローアップで腎機能残存率>95%
– >2.7: 12ヶ月フォローアップで腎機能残存率<80%
1年で10ml/min/1.73m2の低下を認める

U-PCR
• PCRは1日にCreが1g排泄されることを前提に尿中蛋白を推定する方法.
• 随時尿のPCRと24hr蓄尿による蛋白尿の一致率は90-93%(γ値).
8時に再尿した検体ではγ=0.97, 12時ではγ=0.99
• ネフローゼ症候群で大量の蛋白尿を認める場合もγ=0.89-0.94と良好.
(Curr Opin Nephrol Hypertens 2008;17:600–603)
• 1日の総Cre排泄量が1g → 腎不全患者では使えない？
– 98名の非DM性慢性腎障害患者でPCR, 24hr蛋白尿, GFRを評価.
全体 PCR lowest PCR Middle PCR Highest
PCR 2.5[0.2-11.0] 1.0[0.2-0.7] 2.2[1.7-2.7] 4.2[2.7-11.0]
24hr蛋白尿 2.8(1.9) 1.3(0.7) 2.9(1.6) 4.3(1.9)
Cre値(mg/dL) 2.1(0.9) 1.9(0.9) 2.0(0.9) 2.4(1.0)
GFR 48.6(20.8) 54.9(19.4) 53.5(21.6) 35.8(15.8)
– Cre 2台, GFR 35-50程度ならばPCRと蛋白尿の一致性は高いと言える.
PCRが高値なほど, 一致性が低下する傾向にある.
BMJ 1998;316:504–9

variability of repeated test results12%, Ͼ3 g/d. PCR
0.5-3 g/d; and at different Seventy-five percent of when a spot mm Hgis used16 (11)
clinical research, 90-Ͻ100 PCR to indicate6
hresholds. At lower baseline PCRs (Ͻ50 mg/mmol
patients were using either an angiotensin-converting levels or serial PCR results (6) used
protein excretion Ն100 mm Hg 8 are 3
Ͻ442 mg/g]), the maximum range inor angiotensin receptor monitor changes in disease status and response to
enzyme inhibitor variability for a to blocker.
CKD患者のPCR変動
epeated test result was relatively large and exceeded
he baseline value; for example, at a baseline PCR of
PCR Measurements
therapy.
Diabetes present
Cause of CKD
50 (34)
Day-to-day variability may arise due to52 finite set
a (36) 21
17
GN
20 mg/mmol (177 mg/g), a repeated test result could 232 of variables. Proteinuria Kidney Dis. 60(4):561-566.
Mean day-1 PCR was 149.9 Ϯ (SD) mg/mmol Am J is known to show(17)
Diabetes 24 diurnal 8
ange from 0-52 mg/mmol (0-460 mg/g), amean day-2 PCR was 145.9 Ϯ eliminated this source of variation
(1,325 Ϯ 2051 mg/g) and change variation.8 We Other 56 (39) 26
• 安定したCKD患者145名において,
of Ϯ160%. However, at mg/mmol (1,290 PCR of 200
214 a higher baseline Ϯ 1,892 mg/g).from difference by collecting samples at 9:00 AM on
The our study Not available 13 (9) 6
mg/mmol 24hrタンパク尿と朝9:00評価のSpot PCRの変動を評価
(1,768 mg/g), a repeatedbetween day-1 and day-2 PCRs wasdays. Disease progression, regression,
in mean values test result could both collection Kidney transplant 37 (26) 15
ange from 100-300 mg/mmol (884-2,652 mg/g), a CI, Ϫ5.6 to 13.7 alter protein excretion. By restrict-
not significant (4.0 mg/mmol; 95% or treatment may eGFR
hange of Ϯ50%. Variability wasϪ50 to1, 2) mg/g]; P ϭ ing the study to clinically stable patients on stable
– Spot尿は連日評価(Day 121 greater
[35; 95% CI, numerically 0.4). As shown Ն60 mL/min/1.73 m2 46 (32) 29
or those with higher baseline PCRs;was a high correlation medications and collecting mL/min/ on consecutive
in Fig 1, there however, variabil- between day-1 30-Ͻ60 samples 64 (44) 24
ty as a percentage of baseline PCR measurementsless
and day-2 value decreased to (Spearman ϭ risk
– 母集団の24hrタンパク量は0.7g[0.06-35.7] ␳any0.92).of changing m
days,
2
1.73 disease status was effec-
han Ϯ50% for those with baseline PCR Ͼ200 mg/ 15-Ͻ30 mL/min/ 32 (22) 7
tively eliminated. Laboratory 2storage or measurement
• Spot尿の日別の変動はほぼ無い. errors may contribute 1.73 variability;2 however, we
mmol. The repeatability limits didLimits of PCR a fixed
Repeatability not differ by to
m
Ͻ15 mL/min/1.73 m 3 (2)
mount by age (Ͻ55 vs Ն55 years; P ϭ 0.2), sex Naresh1e
The lower and upper limits within stored all samples at Note: Valuesfor no more number48
which 95% of 1°C-4°C
expressed as
than
(p
P ϭ 0.9), or Day 1とDay 2でのPCR値はほぼ一致し, 両者に有意差は認められない.
– eGFR category (P ϭ 0.2).
repeated measurements for the same person in a factor for eGFR in mL/min/1.73 m2 to mL
数値が高い程, stable state should lie were Ϯ 1.96 ϫ 3.594 ϫ
clinically バラツキも大きくなる DISCUSSION
Abbreviations: BP, blood pressure; C
1500
300
Difference in PCR (mg/mmol) (Day 1 minus Day 2)
ease; eGFR, estimated glomerular filtrati
͙A ϭ 7.045͙A, where A is Measurement of proteinuria is of critical imp
tatistical Extrapolation of PCR Test Reliability After the first measurement nephritis.
200
Multiple Tests (Fig 2). The magnitude of the baseline PCRindeter- diagnosis and management of patie
tance the
The reliability of mines PCRmagnitude of thewhen
serial the results improved absolute difference in Althoughthe absolute difference in PC
with CKD. a several methods of measur
Day 2 PCR (mg/mmol)
100
1000
proteinuria are for
repeated test measurement, as shown in Fig 2. The clinically available, all have their o
more test results were averaged and compared with
limitations. Measurement of PCR in repeated ur
absolute The range in or the repeatability coefficient
difference PCR repeat- tainty. Consequently, a a spot m
0
he baseline PCR (Table 2).
that lies outside the 95% repeatabi
bility limits progressively paired serialand this de- is expected is convenient for the patient, less prone
between decreased, measurements sample to lie
-100
500
cally significant and thereby is lik
rease was inversely proportional to the the baseline measurement for
within 1.96 SD from number of collection errors compared with 24-hour collectio
95% of paired measurements.12 Therefore, in a clini- kidney outcomes,6,14 disease status r
of a true change in and consequen
-200
epeated test results averaged and compared with the predictive of
cally This patient, at any baseline recommended ment error. Of the 139 differen
baseline PCR (Table 2). stable was observed consis- PCR, a repeated for routine use by key guideline grou
sample, 133 (95.7%) were Foun
ently at low, medium, result can baseline PCRs.lie within the repeatabil- Average200 day 1 and day2 PCR 400 Kidney 600
test and high be expected to For including NKF-KDOQI (National with
0
0
0 500 1000 1500 of (mg/mmol)

Table 2. Day-to-Day Variability in Spot PCR by PCR Threshold
Approximate 1 Test Before and Average of 2 1 Test Before and Average of 3
Baseline 24-h Protein Baseline 1 Test Before and 1 Test After Tests After Tests After
Range of Excretion PCR
Proteinuria (mg/d) (mg/mmol) Lowera Uppera % Changeb Lowera Uppera % Changeb Lowera Uppera % Changeb
Low 50 5 0 21 320 0 19 280 0 18 260
200 20 0 52 160 0 47 135 0 46 130
Medium 500 50 0 100 100 7 93 86 9 91 82
1,000 100 30 170 70 39 161 61 42 158 58
High 2,500 200 100 300 50 114 286 43 119 281 41
3,000 300 178 422 41 194 406 35 200 400 33
5,000 500 342 658 32 364 636 27 371 629 26
Note: The range of variability at all protein excretion thresholds decreases with repeated test measurements, improving the spot PCR
test’s reliability. Conversion factor for PCR in mg/mmol to mg/g, ϫ8.84.
Abbreviation: PCR, protein-creatinine ratio.
a
Repeatability limits for PCR (in mg/mmol) or the upper and lower range within which 95% of repeated PCR measurements should be
present depend on the number of repeated tests.
b
From baseline.
• 24hrタンパク量別のSpot PCR値. To ascertain whether PCR test reliability could be
hours and ran samples on a single analyzer, including
paired samples in single runs to minimize any risk of improved by repeated testing, we statistically extrapo-
– 初回評価と, 連日の複数回評価. 複数回評価すればその分精度は上昇するが,
this. The coefficient of variation of each laboratory lated and compared the mean of 2 or 3 repeated test
measure of urinary protein and creatinine was Ͻ5%.
一定の誤差はあり得る. results with the baseline PCR (because it was not
Thus, we are confident that the day-to-day variation feasible in this study to conduct multiple repeated
特にタンパク量が多い程誤差も大きい. tests). Although PCR test reliability was improved by
we reported represents inherent test variability under
“ideal” circumstances. Test variability is likely to be doing so, such improvement was modest (Table 2).
of at least this magnitude in the clinic. Our study has several limitations. By design, we
The range in PCR test variability differs substan- included only patients with stable 60(4):561-566. and
Am J Kidney Dis. kidney function
tially with the magnitude of proteinuria: absolute because patients encountered in clinical practice may

DSP, SG, U-P/Cの関係
U-P/C > 500mg/g (≒0.5g/day)を示唆
DSP 1.005 1.010 1.015 1.020 1.025 1.030 1.035 1.040
SG
(-) 5.4% 5.4% 2.9% 1.7% 1.2% 4.7% 0% 0%
(3/56) (12/221) (7/239) (3/174) (2/165) (1/21) (0/8) (0/0)
(±) 62% 25% 27% 7.3% 2.0% 0% 0% 0%
(5/8) (7/28) (11/41) (3/41) (1/49) (0/13) (0/3) (0/0)
(+) 86% 86% 51% 42% 22% 0% 0% 0%
(6/7) (56/65) (41/80) (42/99) (22/100) (0/27) (0/6) (0/2)
(++) 100% 100% 98% 92% 73% 56% 33% 100%
(9/9) (41/41) (78/80) (56/61) (46/63) (10/18) (1/3) (1/1)
(+++) 100% 100% 97% 98% 97% 100% 100% 100%
(2/2) (40/40) (103/106) (124/126) (102/105) (10/10) (6/6) (2/2)

DSP, SG, U-P/Cの関係
U-P/C > 3000mg/g (≒3.0g/day)を示唆
DSP 1.005 1.010 1.015 1.020 1.025 1.030 1.035 1.040
SG
(-) 0% 0.5% 0% 0% 0% 0% 0% 0%
(0/56) (1/221) (0/239) (0/174) (0/165) (0/21) (0/8) (0/0)
(±) 12.5% 3.5% 0% 0% 0% 0% 0% 0%
(1/8) (1/28) (0/41) (0/41) (0/49) (0/13) (0/3) (0/0)
(+) 0% 3.1% 2.5% 0% 0% 0% 0% 0%
(0/7) (2/65) (2/80) (0/99) (0/100) (0/27) (0/6) (0/2)
(++) 44% 34% 13.7% 11.5% 7.9% 0% 0% 0%
(4/9) (14/41) (11/80) (7/61) (5/63) (0/18) (0/3) (0/1)
(+++) 100% 78% 69% 57% 54% 60% 67% 50%
(2/2) (31/40) (73/106) (72/126) (57/105) (6/10) (4/6) (1/2)

DM患者のMicroalbuminuria
• 早朝尿の ACR, AORと24hr蓄尿のAlb値
(Alb/Cr Ratio, Alb/Osmo Ratio) (Am J Kidney Dis 2003;42:685-92)
– ACR, AORは24hr尿中Albと相関する
– 血糖, 性別, 年齢には影響されない
– Microalbuminuriaに対するACR (Alb/Cr Ratio)
Cutoff SN SP PPV NPV
18.4mg/mOsm x102 82% 86% 70% 92%
16.9mg/mOsm x102 85% 78% 61% 93%
– Microalbuminuriaに対するAOR (Alb/Osmo Ratio)
Cutoff SN SP PPV NPV
15.0 mg/g 85% 85% 69% 93%
13.3 mg/g 87% 82% 67% 94%

• 早朝尿のACRの尿中アルブミン尿に対するγ値は0.74-0.96
随時尿を用いるとγ=0.43-0.54まで低下する.
必ず早朝尿を用いる必要がある.
34
Curr Opin Nephrol Hypertens 2008;17:600–603

• Glycosuria
– 試験紙法; ± + ++ +++ ++++
50mg/dL 100mg/dL 250mg/dL 500mg/dL 2000mg/dL
• Ketonuria
– 脂質の代謝産物 DM, 妊娠, 飢餓, 炭水化物制限時に認める
– DKAに対して感度99%, 特異度69%(Ann Emerg Med 1999;34:342-6)
– AKAは尿ケトン陰性でも否定はできない(陽性率は45%[13-89])
(AKAのケトンはβヒドロキシ酪酸; 試験紙法に検知されない)
(DKAではアセト酪酸が多い; 試験紙法に検知される)
• Nitrites
– 細菌が尿中のNitrate(硝酸塩)をNitrite(亜硝酸塩)に分解し生じる
– GNRの殆ど, GPCの一部が分解能を持つ
– 感度は低い(19-48%)が, 特異性は高い(92-100%) (UTIに関して)
– 空気中のN2を感知するため, 長く空気に曝さない

• Leukocyte esterase
– 尿中のWBCに反応する, 5分間はじっくりと反応させるとGOOD
– 更に WBC castは腎の感染症を示唆する
– 培養陰性UTIはChlamydia, Ureaplasma urealyticumを考える
• Bilirubin, Urobilinogen
– 直接Bilが尿中へ排泄される
– 直接Bil 消化管にてUrobilinogen 再吸収 尿中排泄
★ 便秘ではUrobilinogen 上昇,
下痢, 腸管通過性亢進ならば低下する
★ 胆道閉鎖ではUrobilinogen 低下