尿検査1

  • 2,486 views
Uploaded on

 

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
No Downloads

Views

Total Views
2,486
On Slideshare
0
From Embeds
0
Number of Embeds
4

Actions

Shares
Downloads
0
Comments
0
Likes
2

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. UrinalysisAFP 2005;71:1153-62 高岸 勝繁
  • 2. 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
  • 3. 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
  • 4. 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. 5
  • 6. • 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
  • 7. • 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↑
  • 8. 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 < 5.1Blood ヘモグロビン尿, ミオグロビン尿 タンパク尿, Vit CGlu 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 PhenazopyridineSG デキストラン, 造影剤, 蛋白尿 アルカリ尿Urobilinogen Nitrite↑, Phenazopyridine
  • 9. 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
  • 10. 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
  • 11. 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
  • 12. 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; 198:1256–1265Ultrasound 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 innostic 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 nowfor 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 overcomparison 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 13sound 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 NAtumors 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 54trasound 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 32stone detectionb[38, 39], but its600 Lang et al. [17] sensitivity for 600 7.3 0 NA CT urography provides detailed informa- NA 43combined 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 43dilatation 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 24combination 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 ReferenceUltrasound 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 79nonurologic diseases. A large study showed hanced CT for stone disease but does not cretory urography for stone diagnosis [44]. Edwards et al. [13] 4020 2071a high specificity but moderate sensitivity miss significant disease.0Studies foundmen; 1% women hematuria, multiple studies have now 19 6.7% sensi- For NA 27forSultana 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 35comparisonal. [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% womensound 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 36tumors and equal (i.e., moderate) sensitivity ic imaging, sensitivity for the combination er than 3 cm for excretory urography [45]. Retrospectivefor 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 NAstone detection [38, 39], but its sensitivity for Hovius et al. [20] 1509 1032 23 ≠ 0 NA CT urography provides detailed informa- NA 60combined 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
  • 13. • 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/dL0-1/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
  • 14. • 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
  • 15. 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 <30PCR; >=40yr <40yr Prot/Cr <50 異常なし 異常ありeGFR >=60ml/mimBP < 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
  • 16. • 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
  • 17. (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 monthsNegative 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 primaryNo further urologic Evaluate for primary Repeat complete Repeat complete monitoring renal disease monitoring renal disease evaluation evaluationGlomerular bleeding or “Isolated hematuria” Glomerular bleeding or “Isolated hematuria” proteinuria proteinuria Renal biopsy Biopsy controversial Renal biopsy Biopsy controversial
  • 18. • 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
  • 19. • 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
  • 20. raphy [52–54], with relatively the lowest de- ity for better tissue characterization than oth- In contrast, CT urography is associatedtection 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 theTABLE 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
  • 21. • 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(+)
  • 22. • 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)
  • 23. 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)
  • 24. 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
  • 25. 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
  • 26. 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)
  • 27. 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
  • 28. 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
  • 29. 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 GN20 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) 6mg/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, wemmol. 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. 200Multiple 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 omore 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 differenbaseline 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)
  • 30. 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 PCRProteinuria (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 PCRtest’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 bepresent 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 behours and ran samples on a single analyzer, includingpaired 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 testmeasure 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 notThus, 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 bywe 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 functiontially with the magnitude of proteinuria: absolute because patients encountered in clinical practice may
  • 31. 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)
  • 32. 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)
  • 33. 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%
  • 34. • 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. 34Curr Opin Nephrol Hypertens 2008;17:600–603
  • 35. • 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
  • 36. • 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