Haematuria

Blood may originate from the kidney or the collecting system. Urine testing for haematuria should only be performed for identifiable clinical reasons; there is currently no evidence to support opportunistic screening of the general population.¹

• Visible haematuria (VH): also called macroscopic haematuria or gross haematuria.
• Non-visible haematuria (NVH): also called microscopic haematuria or dipstick positive haematuria:
  • Symptomatic non-visible haematuria (s-NVH): associated symptoms include voiding lower urinary tract symptoms (LUTS): hesitancy, frequency, urgency, dysuria.
  • Asymptomatic non-visible haematuria (a-NVH): incidental detection in the absence of LUTS or upper urinary tract symptoms.
• Significant haematuria is defined as:
  • Any single episode of VH.
  • Any single episode of s-NVH (in absence of UTI or other transient causes).
  • Persistent a-NVH (in absence of UTI or other transient causes). Persistence is defined as 2 out of 3 dipsticks positive for NVH.

• The prevalence of asymptomatic microscopic haematuria varies from 0.19 percent to as high as 21 percent.²
• In one study of 1,000 patients with haematuria (but no proteinuria), the common causes of haematuria were inflammatory conditions of the urethra and prostate, benign prostatic hypertrophy, cystitis, transitional carcinoma of the bladder, and stones in the renal pelvis or ureter. 8% had some form of renal tract malignancy.³
• In a screening study of men aged over 50 years, pathological conditions were found in 31 out of 44 who had haematuria at least once on serial testing. One-third of the 44 had either cancer of the urinary tract or other conditions requiring immediate treatment.

Common causes include urinary tract infection, bladder tumours, urinary tract stones, urethritis, benign prostatic hypertrophy and prostate cancer.

• Infection: cystitis, tuberculosis, prostatitis, urethritis, schistosomiasis, infective endocarditis.
• Tumour: renal carcinoma, Wilms' tumour, carcinoma of the bladder, prostate or urethra.
• Trauma: renal tract trauma due to accidents, catheter or foreign body, prolonged severe exercise, rapid emptying of an overdistended bladder (e.g. after catheterisation for acute retention).
• Inflammation: glomerulonephritis, Henoch-Schonlein purpura, IgA nephropathy, Goodpasture's syndrome, polyarteritis, post-irradiation.
• Structural: calculi (renal, bladder, ureteric), simple cysts, polycystic renal disease, congenital vascular anomalies.
• Haematological: sickle cell disease, coagulation disorders, anticoagulation therapy.
• Surgery: invasive procedures to the prostate or bladder.
• Toxins: sulphonamides, cyclophosphamide, non-steroidal anti-inflammatory drugs.
• Others: genital bleeding, including child abuse; menstruation; factitious (including Munchausen by proxy).

Other causes of red or dark urine:

• Haemoglobinuria: dipstick positive but no red cells on microscopy
• Myoglobinuria
• Food, e.g. beetroot
• Drugs, e.g. rifampicin, nitrofurantoin, senna
• Porphyria: urine darkens on standing
• Bilirubinuria: obstructive biliary disease

• Take a full urological history and include palpation of the abdomen and blood pressure.
• Features suggesting a renal cause include hypertension, altered renal function tests, proteinuria, known previous renal problems, renal mass and glomerular red cells in urine.
• Haematuria without proteinuria does not necessarily indicate a non-glomerular origin as glomerular bleeding is not necessarily accompanied by proteinuria.⁴

Transient causes that need to be excluded before establishing the presence of significant haematuria are urinary tract infection (UTI), exercise induced haematuria or rarely myoglobinuria, and menstruation.¹

• All children with haematuria should be referred.
• All definite haematuria, whether macroscopic or microscopic, requires investigation to exclude serious underlying conditions, especially urinary tract neoplasm.⁵
• Patients on anticoagulants should also be investigated. Anticoagulants are more likely to provoke rather than be the cause of haematuria.

Initial investigations for a patient with s-NVH and persistent a-NVH¹

• Exclude UTI and/or other transient cause.
• Plasma creatinine and estimated glomerular filtration rate (eGFR).
• Measure proteinuria: send urine for protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR) on a random sample (according to local practice). 24 hour urine collections for protein are rarely required. An approximation to the 24 hour urine protein or albumin excretion (in milligrams) is obtained by multiplying the ratio (in mg/mmol) x10.
• Measurement of blood pressure.

• Check full blood count (anaemia) and clotting screen
• Urine red cell morphology: dysmorphic erythrocytes suggest a renal origin
• Cytological examination of urine⁶

Indications for urology referral¹

• Direct referral to urology for further investigation is required for:
• All patients with visible haematuria; a nephrology referral may be considered more appropriate if glomerulonephritis is suspected.
• All patients with s-NVH (any age).
• All patients with a-NVH aged ≥40 years.

Indications for nephrology referral¹

• For patients who have had a urological cause excluded or have not met the referral criteria for a urological assessment, a nephrology referral should be considered.
• Evidence of declining GFR (by greater than 10 ml/min at any stage within the previous 5 years or by greater than 5 ml/min within the last 1 year).
• Stage 4 or 5 chronic kidney disease (eGFR less than 30 ml/min).
• Significant proteinuria (ACR 30mg/mmol or higher, or PCR 50mg/mmol or higher)
• Isolated haematuria (i.e. in the absence of significant proteinuria) with hypertension in those aged younger than 40 years.
• Visible haematuria coinciding with intercurrent (usually upper respiratory tract) infection.

Long term monitoring of patients with haematuria¹

Patients not meeting criteria for referral or who have had negative urological or nephrological investigations (including all of : eGFR 60 ml/min or higher, and ACR less than 30 or PCR less than 50, and blood pressure less than 140/90) need long term monitoring due to the uncertainty of the underlying diagnosis. Patients should be monitored for the development of:

• Voiding lower urinary tract symptoms (LUTS)
• Visible haematuria
• Significant or increasing proteinuria
• Progressive renal impairment (falling eGFR)
• Hypertension (the development of hypertension in older people may have no relation to the haematuria).

• Referral or re-referral to urology is indicated if development of VH or s-NVH.¹
• Referral to nephrology if:¹
  • Significant or increasing proteinuria (ACR higher than 30 or PCR higher than 50)
  • eGFR less than 30 ml/min (confirmed on at least 2 readings and without an identifiable reversible cause)
  • Deteriorating eGFR (by greater than 5 ml/min fall within 1 year, or greater than 10 ml/min fall within 5 years)

NICE referral guideline

The NICE Cancer Referral Guidelines recommend urgent referral for:⁷

• Patients of any age with painless macroscopic haematuria.
• Aged 40 years and older who present with recurrent or persistent urinary tract infection associated with haematuria.
• Aged 50 years and older who are found to have unexplained microscopic haematuria.
• With an abdominal mass identified clinically or on imaging that is thought to arise from the urinary tract.

Further investigations

• Ultrasound of renal tract: if urinalysis does not explain the findings. Ultrasound is as sensitive as intravenous urography and more cost-effective.⁸ A plain film of the abdomen should also be obtained, mainly to rule out urinary calculi.
• Cystoscopy: important in younger as well as older patients. One study looking at almost 2,000 patients with haematuria found bladder cancer in 7 patients younger than 40 years.⁹
• Intravenous urography is indicated if urinary tract stones are suspected or if ultrasound, abdominal x-ray and cystoscopy are negative.
• Renal angiography, CT scanning or renal biopsy are indicated in specific circumstances.

1. Joint Consensus Statement on the Initial Assessment of Haematuria, Renal Association and British Association of Urological Surgeons (July 2008)
2. Grossfeld GD et al; Asymptomatic Microscopic Hematuria in Adults: Summary of the AUA Best Practice Policy Recommendations. Am Fam Physician; 2001 Mar 15;63(6):1145-54.
3. Mariani AJ, Mariani MC, Macchioni C, et al; The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. J Urol. 1989 Feb;141(2):350-5. [abstract]
4. Savige J, Buzza M, Dagher H; Haematuria in asymptomatic individuals. BMJ. 2001 Apr 21;322(7292):942-3.
5. Marazzi P, Gabriel R; The haematuria clinic. BMJ. 1994 Feb 5;308(6925):356.
6. Hofland CA, Mariani AJ; Is cytology required for a hematuria evaluation? J Urol. 2004 Jan;171(1):324-6. [abstract]
7. Referral for suspected cancer, NICE Clinical Guideline (2005)
8. Spencer J, Lindsell D, Mastorakou I; Ultrasonography compared with intravenous urography in investigation of urinary tract infection in adults. BMJ. 1990 Jul 28;301(6745):221-4. [abstract]
9. Khadra MH, Pickard RS, Charlton M, et al; A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol. 2000 Feb;163(2):524-7. [abstract]

• Rodgers M et al; Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation. Health Technology Assessment 2006; Vol 10: number 18.
• Chronic kidney disease, NICE Clinical Guideline (September 2008); Early identification and management of chronic kidney disease in adults in primary and secondary care