Haematuria in Primary Care


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  • Phosphates disappear on urine acid Cloudy Phosphates (add acid) Urates (add alkali)
  • Microscopic haematuria 10% false positive (heavy bacteriuria, semen, pH>9 eg with oxidising agents to clean perineum, dilute urine (SG < 1.00009) False negative high dose vitamin C Urine dipstick Chemical dipsticks detect haem (intact red cells, free haemoglobin, or free myoglobin); theyprovide aninstant result and are used to detect non-visible haematuria in primary care.10 Chemical dipsticks are available from several manufacturers and are read visually or using automated systems on a semi-quantitative scale. Although it is difficult tointerpret studiesonthe efficiency of this test because of inherent design and reporting bias, analysis of pooled data sets indicates that it is a reasonable way to detect non-visible haematuria in primary care (positive likelihood ratio 5.99 (95% confidence interval 4.04 to 8.89), negative likelihood ratio 0.21 (0.17 to 0.26)).1 The detection of trace haematuria can be considered negative because the threshold for significance isprobably less thanthree to five redblood cellsper high power field.16 A positive result in a haemolysed sample should be treated the same as in a nonhaemolysed Urine microscopy Red blood cell counts have been used to define microscopic haematuria, and cut-off points have varied (including ≥2 cells per high power field and ≥5 cells per high power field).17 18 Microscopy provides an accurate measure of red blood cellswhen assessed by trained technicians or nephrologists in fresh voided early morning midstream specimens of urine.19 20 However, time to analysis affects the integrity of red blood cells.21 In a prospective multicentre study, red blood cell counts dropped by 5-9% at five hours, 11-28% at 24 hours, and 29- 35% at 72 hours.22Because immediatemicroscopy is not feasible in primary care, the accuracy of quantitative red blood cell microscopy is questionable. In general practice, it is therefore not logical, and rarely necessary, to validate dipstick haematuria by urine microscopy.
  • Urinary protein:creatinine ratio ≥ 50 mg/mmol Urinary albumin:creatinine ratio ≥ 30 mg/mmol For 24 hour urine protein level, multiply by 10 Persistent non-visible haematuria can have urological or nephrological causes (box 3). The most important urological causes include cancer and calculus disease, which are seen in about 5% and 8% of patients, respectively.910
  • Non-visible haematuria is present in about 2.5% of the general population, although it can be as high as 20%, depending on features of the study population, such as age, sex, the presence of risk factors for disease, and the definition used.12-14 Within cohorts of patients with asymptomatic non-visible haematuria detected by screening, the overall incidence of serious conditions such as urological malignancy is <1.5%,12 so the consensus is that population screening is not warranted. In contrast, a cause for nonvisible haematuria is found in about 15% of cases selected for referral from primary care to haematuria clinics.9 10 These cases will usually have had an indication for urine testing, such as urinary tract symptoms.15 There is currently no evidence to support opportunistic testing for haematuria without a clinical reason.
  • In low risk and < 40 years, cystoscopy pick up is only 1%
  • Haematuria in Primary Care

    1. 1. Haematuria Marc Laniado MD FRCS(Urol) FEBU www.windsorurology.co.uk
    2. 2. Types of Haematuria <ul><li>Visible or non visible </li></ul><ul><li>Symptomatic or asymptomatic </li></ul>
    3. 3. Symptomatic v Asymptomatic <ul><li>Symptomatic means haematuria associated with lower or upper urinary tract symptoms </li></ul>
    4. 4. Visible haematuria or coloured urine? <ul><li>Yellow-orange </li></ul><ul><ul><li>Rifampicin </li></ul></ul><ul><li>Brown </li></ul><ul><ul><li>Nitrofurantoin </li></ul></ul><ul><ul><li>Senna </li></ul></ul><ul><li>Reddish brown </li></ul><ul><ul><li>L-dopa </li></ul></ul><ul><ul><li> -methyl dopa </li></ul></ul><ul><ul><li>metronidazole </li></ul></ul><ul><li>Red </li></ul><ul><ul><li>Red cells </li></ul></ul><ul><ul><li>Beet </li></ul></ul><ul><ul><li>Phenolphthalein in laxatives </li></ul></ul><ul><ul><li>Phenothiazine (prochlorperazine) </li></ul></ul><ul><ul><li>Doxorubicin </li></ul></ul><ul><ul><li>Vegetable dyes </li></ul></ul><ul><ul><li>Concentrated urates </li></ul></ul><ul><ul><li>Myoglobinuria </li></ul></ul><ul><ul><li>Hemoglobinuria </li></ul></ul>
    5. 5. Non-visible haematuria: false positive & negatives <ul><li>Non-Visible Haematuria </li></ul><ul><ul><li>Dipstick Haematuria </li></ul></ul><ul><ul><ul><li>+, ++, +++ significant </li></ul></ul></ul><ul><ul><ul><li>91% sensitivity </li></ul></ul></ul><ul><ul><ul><ul><li>false -: high vit C intake) </li></ul></ul></ul></ul><ul><ul><ul><li>70% specificity </li></ul></ul></ul><ul><ul><ul><ul><li>false + heavy bacteriuria, semen, pH>9 eg with oxidising agents to clean perineum, dilute urine (SG < 1.00009) </li></ul></ul></ul></ul><ul><ul><ul><li>No distinction between non-haemolysed or haemolysed </li></ul></ul></ul><ul><ul><li>Microscopic haematuria </li></ul></ul><ul><ul><ul><li> 3 RBC/high-power field </li></ul></ul></ul><ul><ul><ul><ul><li>Observer error </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Storage reduces sensitivity </li></ul></ul></ul></ul><ul><ul><ul><li>Not necessary in primary care </li></ul></ul></ul>
    6. 6. Criteria for significant haematuria criteria Visible (Macroscopic) Non-visible (3 urine dipstick over 2 to 3 weeks) Symptomatic “ s-VH” Significant if ≥1 episodes contain blood “ s-NVH” Significant if ≥1 of 3 samples dipstick +ve Asymptomatic “ a-VH” Significant if ≥1 episodes contain blood “ a-NVH” Significant if ≥ 2 of 3 urine samples dipstick +ve
    7. 7. Visible Haematuria: Referral Criteria <ul><li>Frank painless haematuria </li></ul><ul><ul><li>All need referral under 2 week rule (any age) </li></ul></ul><ul><li>Painful haematuria & UTI </li></ul><ul><ul><li>Refer all men with even 1 episode </li></ul></ul><ul><ul><li>If persistent, refer urgently haematuria clinic </li></ul></ul><ul><ul><li>If 3 UTI in 12 months, urgent referral to haematuria clinic even if clears on antibiotics </li></ul></ul><ul><ul><li>If single episode with probable UTI, treat & re-evaluate for NVH on 3 further occasions in women. Follow NVH pathway </li></ul></ul><ul><li>Patients on warfarin should also be referred </li></ul>
    8. 8. Non-Visible Haematuria (NVH) initial investigations <ul><li>Exclude transient causes </li></ul><ul><ul><li>Exercise, UTI, menstrual blood, myoglobinuria </li></ul></ul><ul><li>UTI </li></ul><ul><ul><li>Treat & retest </li></ul></ul><ul><ul><li>Women with repeated UTI need referral (5% of bladder cancers present as UTI) </li></ul></ul><ul><ul><li>All men with haematuria and UTI need referral (even 1, any age) </li></ul></ul><ul><li>≥ 2 of 3 dipstick positive – Refer to renal physicians if any below eGFR ↓ or protein ↑ in urine </li></ul><ul><ul><li>eGFR (< 60 ml/min abnormal) </li></ul></ul><ul><ul><li>Urinary protein:creatinine ratio ≥ 50 mg/mmol </li></ul></ul><ul><ul><li>Urinary albumin:creatinine ratio ≥ 30 mg/mmol </li></ul></ul><ul><ul><li>Check blood pressure especially in young patients </li></ul></ul>
    9. 9. a-NVH referral criteria to haematuria clinic <40 years 40-50 years >50 years Asymptomatic NVH (a-NVH) risk factors for significant disease  refer to haematuria clinic, otherwise monitor Routine referral to haematuria clinic Urgent Referral under 2 week wait Symptomatic (s-NVH) Routine referral to haematuria clinic Routine referral to haematuria clinic Urgent Referral under 2 week wait
    10. 10. Risk factors for significant disease <ul><li>Smoking </li></ul><ul><li>History of pelvic irradiation </li></ul><ul><li>Occupational exposure </li></ul><ul><ul><li>dyes, benzenes, aromatic amines, leather, dyes, tires, rubber </li></ul></ul><ul><ul><li>autoworker, painter, truck driver, drill press operator, leather worker, metal worker, and machiners, </li></ul></ul><ul><ul><li>occupations that involve organic chemicals: dry cleaner, paper manufacturer, rope and twine maker, dental technician, barber or beautician, physician, worker in apparel manufacturing, and plumber </li></ul></ul><ul><li>Cyclophosphamide </li></ul><ul><li>History of urologic disorder or disease </li></ul><ul><li>Urgency/bladder pain/frequency </li></ul><ul><li>History of urinary tract infection </li></ul><ul><li>Analgesic abuse </li></ul><ul><li>Laxatives causing renal disease </li></ul><ul><li>Aristolochic acid use (herbal weight loss remedies) </li></ul><ul><li>Gonorrhoea (bladder cancer) </li></ul>
    11. 11. Nephrology Referral <ul><li>↑ Urinary Protein:creatinine > 50 mg/mmol or albumin:creatinine ration > 30 mg/ml </li></ul><ul><li>Declining GFR by ≥ 10 ml/min within last 5 years or by > 5 ml/min in last year </li></ul><ul><li>eGFR < 30 ml/min CKD4 </li></ul><ul><li>Isolated haematuria with hypertension if age < 40 years </li></ul><ul><li>Visible haematuria with intercurrent infection (usually URTI) </li></ul>
    12. 12. Long term monitoring of haematuria of unknown aetiology in primary care <ul><li>Indications </li></ul><ul><ul><li>Not meeting criteria for immediate referral </li></ul></ul><ul><ul><li>Negative urological or nephrological investigations </li></ul></ul><ul><li>Monitor (annually at least) for </li></ul><ul><ul><li>Development of s-NVH in a patient with a-NVH </li></ul></ul><ul><ul><li>Lower urinary tract symptoms </li></ul></ul><ul><ul><li>Visible haematuria (development of persistent) </li></ul></ul><ul><ul><li>Proteinuria (worsening or development) </li></ul></ul><ul><ul><li>Falling eGFR </li></ul></ul><ul><ul><li>High blood pressure </li></ul></ul>6 -12 monthly
    13. 13. Algorithm
    14. 14. Voided Markers of TCC <ul><li>Nuclear Matrix Protein 22 </li></ul><ul><ul><li>Much more sensitive (73%) than cytology (33%) </li></ul></ul><ul><ul><ul><li>Cannot replace imaging </li></ul></ul></ul><ul><ul><li>Less specific (80%) than cytology (99%) </li></ul></ul>
    15. 15. Imaging <ul><li>IVU </li></ul><ul><ul><li>False negative </li></ul></ul><ul><ul><ul><li>renal masses  3 cm and </li></ul></ul></ul><ul><ul><ul><li>anterior/posterior masses </li></ul></ul></ul><ul><ul><li>Cannot distinguish solid from cystic </li></ul></ul><ul><li>Ultrasound </li></ul><ul><ul><li>Misses renal masses  3 cm </li></ul></ul><ul><li>CT </li></ul><ul><ul><li>Spiral CT </li></ul></ul><ul><ul><ul><li>Much more sensitive for calculi (98% cf IVU 55%, USS 20%) </li></ul></ul></ul><ul><ul><li>CT urography </li></ul></ul><ul><ul><li>Preferable & Cheaper than combination of IVU and CT? </li></ul></ul>
    16. 17. CT Most Accurate
    17. 18. Cystoscopy <ul><li>Indications </li></ul><ul><ul><li>Age  40 </li></ul></ul><ul><ul><li>All with risk factors for bladder cancer including those with benign cause found in upper tract </li></ul></ul><ul><li>Substitute with cytology/NMP22? </li></ul><ul><ul><li>Age < 40 years & no risk factors for malignancy </li></ul></ul><ul><li>Flexible or rigid cystoscopy </li></ul>
    18. 19. Interstitial Cystitis Stones BPH Cancer
    19. 20. Algorithm