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JukkaSairanen
SariAaltonen

Haematuria

Essentials

  • Exclude urinary tract infection and blood contamination (e.g. menstruation, sexual trauma, preceding catheterization).
  • Initial investigations of haematuria are performed in primary health care, further investigations as needed in specialized care.
  • Further urological assessment should be carried out in all patients with macroscopic haematuria that is not explained by the above causes Macroscopic Haematuria in the Diagnosis of Urological Cancers.
  • In asymptomatic isolated microhaematuria, no further urological assessment is normally required.

Definition

Macroscopic haematuria

  • Urine that is stained visibly red. Already 1 ml blood / 1 000 ml urine causes macroscopic haematuria.
  • Red coloured urine may also be caused by
    • certain foods (beetroot)
    • medication (nitrofurantoin, rifampicin)
    • acute porphyria Porphyrias.

Microscopic haematuria

  • Urine is not visibly red, but blood can be detected in dipstick test or microscopy.
  • See also article Urinalysis and bacterial culture Urinalysis and Bacterial Culture.
  • A dipstick test is sensitive, and a positive result must be confirmed by particle counting (× 2).
    • Haemoglobinuria or myoglobinuria may also give positive reactions.
    • Reducing agents (such as ascorbic acid) reduce or even inhibit the staining reaction.
  • Particle counting
    • More than 3 erythrocytes/high power field in sediment analysis
    • More than 5 erythrocytes/0.9 mm3 in counting chamber
    • More than 15 × 106 erythrocytes/l in particle counting by flow cytometry

Diagnostic work-up

  • When patients report blood in urine, they are usually right.

Medical history

  • Is haematuria continuous (glomerulonephritis, tumours in the urinary tract), periodic (IgA nephropathy) or transient (urinary calculi)?
  • In what circumstances was haematuria noted (fever, physical activity)?
  • Does the patient have any general symptoms, such as prolonged mild fever, joint or abdominal pain, rash (vasculitic disorders, SLE)?
  • Are there any other symptoms (increased urinary frequency, dysuria, lower abdominal or flank pain)?
    • Cystitis or nephritis, urolithiasis, prostatitis, tumour, polycystic kidney disease
  • Is haematuria seen at the initiation of, throughout or only at the end of voiding?
    • Blood at the initiation of voiding suggests a urethral pathology, continuous haematuria a renal or ureteral problem and blood at the end a bladder pathology.
  • Are there any hereditary diseases or a tendency to urinary calculus formation in the family?
  • Does the patient smoke?
  • Travel abroad (schistosomiasis Schistosomiasis (Bilharziasis), malaria Diagnosis and Treatment of Malaria etc.)
  • Analgesics or cytostatic chemotherapy Adverse Effects of Antineoplastic Agents? These drugs may cause interstitial nephritis (analgesics), interstitial cystitis or uroepithelial cancer (cytostatic agents).
    • Microhaematuria after pelvic floor radiotherapy or cytostatic chemotherapy should be investigated.
  • Blood coagulation disorders or anticoagulants (overdose of warfarin, abnormal coagulation)?

Clinical findings

  • Petechiae (Henoch-Schönlein purpura, vasculitic disorders), bruising and enlarged lymph nodes (bleeding tendency, inflammation, malignancies)
  • Blood pressure (glomerulonephritis)
  • Abdominal palpation (size and contour of the liver, spleen and kidneys: malignancies, polycystic kidney disease)
  • Palpation of the prostate via the rectum (prostatitis, prostatic hyperplasia, prostatic cancer)

Investigations and strategy

Macroscopic haematuria

  • The most common aetiologies in adults are urinary tract infections Urinary Tract Infections, tumours of the urinary tract (especially bladder cancer Bladder Cancer), benign prostatic hyperplasia Benign Prostatic Hyperplasia, prostatic cancer Prostate Cancer, renal parenchymal diseases, contaminated collection of a sample and urinary calculi Urinary Calculi.
  • The cause of macroscopic haematuria can be found in over 90% of the cases.
  • The most important diseases to be excluded are tumours of the urinary tract and glomerular diseases.
  • Patients should always be referred for further urological assessment unless haematuria is caused by a urinary tract infection or by blood contamination. It is advisable to order exfoliative urinary cytology and ultrasound scanning of the kidneys as preparatory investigations.
  • The first-line investigation in hospital is often CT urography if there are no contraindications for it (radiation burden, contrast medium).
  • If IgA nephropathy is suspected (concurrent proteinuria, reduced eGFR, high blood pressure), refer the patient to a nephrologist.
  • Macrohaematuria associated with urinary tract infection does not require further examinations if there is no haematuria after the infection has cleared.

Microscopic haematuria

  • Often an asymptomatic incidental finding.
  • May result from the same aetiologies as macroscopic haematuria. Reveals urinary tract tumours poorly, but is often associated with diseases of the prostate. If there are general symptoms, a glomerular disease should be sought.
  • Asymptomatic microscopic haematuria generally does not necessitate further investigations, but the decision should be made on an individual basis, taking into account the risk factors for bladder cancer, such as smoking, chemical exposure and age. Microcopic haematuria in a patient below 40 years of age does not require further investigations.
  • The only first symptom of renal vasculitis Vasculitides may sometimes be microscopic haematuria. Sometimes vasculitis can be limited to the kidneys, i.e. there are no systemic symptoms. As an investigation to exclude ANCA-associated vasculitis, proteinase 3 antibodies and myeloperoxidase antibodies may be determined.
  • Laboratory tests should be done based on medical history and clinical findings.
    • Basic blood count with platelet count, ESR, CRP, plasma creatinine and eGFR, plasma PSA
    • Bacterial culture and chemical screening of urine: is there proteinuria?
    • Urinary cytology: erythrocyte morphology, casts, leucocytes
      • The shape of erythrocytes may help to localize the source of bleeding. Symmetric, smooth red blood cells (RBCs) of the same size usually originate in the lower urinary tract, whereas dysmorphic RBCs originate in the glomeruli.
      • If in microscopic haematuria erythrocyte morphology (acanthocytes, casts) suggests a glomerular aetiology in a patient with no proteinuria or renal failure (normal eGFR), no further examinations are required. Annual monitoring of blood pressure, chemical screening of urine and urinary cytology is indicated for a period of 5 years, for example (to detect possible development of glomerulonephritis).
      • Sterile pyuria (leucocyturia)
        • Urinary calculi and tumours
        • Genitourinary tuberculosis (culture for tubercle bacilli in urine)
        • Concurrent proteinuria is usually suggestive of a renal parenchymal disease.
    • Exfoliative urinary cytology should be considered in patients who are over 40 or have factors increasing susceptibility to bladder cancer, such as smoking, unless other causes for haematuria can be demonstrated. Haematuria in a young patient is usually caused by urinary tract infection, calculi or renal parenchymal disease, particularly IgA nephropathy, whereas malignancy must be considered in patients over the age of 40 years already.
    • Ultrasound scanning of the urinary tract may be diagnostic in both microscopic and macroscopic haematuria (tumour, calculi, polycystic kidney disease).

Further investigations in specialized health care

  • Referral to nephrologist (for possible renal biopsy)
    • Recurrent or constant microscopic haematuria associated with
      • general symptoms (prolonged mild fever, joint symptoms, rash)
      • proteinuria
      • impaired renal function
      • high blood pressure, particularly in young patients
      • positive antineutrophil cytoplasmic antibodies (ANCA) or other systemic disease suspicion
  • Referral to urologist (for possible cystoscopy)
    • If the patient has had macroscopic haematuria (without findings suggesting IgA nephropathy, i.e. transient macroscopic haematuria in association with an upper respiratory tract infection) or the patient has risk factors for bladder cancer (smoking, occupational exposure, history of cyclophosphamide treatment)
    • Suspicious cells in cytology
    • Ultrasound examination suggestive of bladder pathology
  • Other imaging studies to be performed as considered appropriate by a nephrologist or a urologist
    • CT urography (investigation of choice for suspected urinary calculi or tumour of the upper urinary tract)
    • Angiography, investigation of renal function by radioisotope renography
    • MRI

    References

    • Sethi S, De Vriese AS, Fervenza FC. Acute glomerulonephritis. Lancet 2022;399(10335):1646-1663. [PubMed]

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