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?
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)?
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?
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]