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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Haematuria (blood in the urine) 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, although it is being considered in conjunction with other bladder cancer markers in the UK.
- 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 urinary tract infection (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 NVH in the population varies from 2.4% to 31.1%. The highest rates are in men older than 60 years and men who are current or past smokers.
There is evidence for an association between glomerular haematuria and adverse renal outcomes.
Common causes of haematuria include UTI, bladder tumours, urinary tract stones, urethritis, benign prostatic hypertrophy (BPH) and prostate cancer.
The most common causes of a-NVH are UTI, BPH and urinary calculi. However, up to 5% of patients with NVH are found to have a urinary tract malignancy.
- Infection: cystitis, tuberculosis, prostatitis, urethritis, schistosomiasis, infective endocarditis.
- Tumour: renal carcinoma, Wilms' tumour, carcinoma of the bladder, prostate cancer, urethral cancer or endometrial cancer.
- Trauma: renal tract trauma due to accidents, catheter or foreign body, prolonged severe exercise, rapid emptying of an overdistended bladder (eg, after catheterisation for acute retention).
- Inflammation: glomerulonephritis, Henoch-Schönlein 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 gland or bladder.
- Toxins: sulfonamides, cyclophosphamide, non-steroidal anti-inflammatory drugs.
- Others: genital bleeding, including child abuse; menstruation; Münchhausen's syndrome or fabricated or induced illness by carers.
- 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 (red cells with irregular contours and shape) in the urine.
- Haematuria without proteinuria does not necessarily indicate a non-glomerular origin, as glomerular bleeding is not necessarily accompanied by proteinuria.
Other causes of red or dark urine:
- Haemoglobinuria: dipstick-positive but no red cells on microscopy.
- Food - eg, beetroot.
- Drugs - eg, rifampicin, nitrofurantoin, senna.
- Porphyria: urine darkens on standing.
- Bilirubinuria: obstructive biliary disease.
Investigations of haematuria
Transient causes that need to be excluded before establishing the presence of significant haematuria are UTI, exercise-induced haematuria or, rarely, myoglobinuria, and menstruation.
- All children with haematuria should be referred.
- All definite haematuria, whether VH or NVH, requires investigation to exclude serious underlying conditions, especially urinary tract neoplasm.
- 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-NVH
- 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) x 10.
- Measurement of blood pressure.
Other initial investigations
These may include:
- FBC (anaemia) and clotting screen.
- Urine red cell morphology: dysmorphic erythrocytes suggest a renal origin.
Urine cytology, once thought to be contributory, is now performed less often. It can miss a significant number of muscle-invasive bladder cancer and high-risk disease. The role of urine cytology in select cases should also be considered in the context of the impact of a false positive result leading to further potentially invasive tests conducted under general anaesthesia.
Indications for urological referral
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 nephrological referral
- For patients who have had a urological cause excluded or have not met the referral criteria for a urological assessment, a referral to nephrology should be considered.
- < Age 40 and:
- eGFR <60ml/minute.
- Significant proteinuria (ACR 30 mg/mmol or higher, or PCR 50 mg/mmol or higher).
- BP>140/90 mm Hg.
Long-term monitoring of patients with haematuria
While haematuria persists, the patient should be monitored annually with eGFR, BP and ACR/PCR.
Referral or re-referral to urology should occur if there VH or s-NVH.
Referral to nephrology should occur if there is:
- Significant or increasing proteinuria (ACR higher than 30 mg/mmol or PCR higher than 50 mg/mmol).
- eGFR less than 30 ml/minute (confirmed on at least two readings and without an identifiable reversible cause).
- Deteriorating eGFR (by greater than 5 ml/minute fall within one year, or greater than 10 ml/minute fall within five years).
National Institute for Health and Care Excellence (NICE) referral guidance
NICE cancer referral guidelines recommend:
- Refer people using a suspected cancer pathway referral (for an appointment within two weeks) for:
- Bladder or renal cancer: haematuria (visible and unexplained) either without UTI or that persists or recurs after successful treatment of UTI (patients aged 45 and over).
- Bladder cancer: haematuria (non-visible and unexplained) with dysuria or raised white cell count on a blood test (patients aged 60 and over).
- Consider non-urgent referral for bladder cancer in people aged 60 and over with recurrent or persistent unexplained UTI.
- Endometrial cancer: haematuria (visible) with low haemoglobin levels or thrombocytosis or high blood glucose levels or unexplained vaginal discharge in women aged 55 years and over - consider a direct access ultrasound.
- Prostate cancer: haematuria (visible) in men. Consider a prostate-specific antigen (PSA) test and digital rectal examination.
- Ultrasound of the renal tract: if urinalysis does not explain the findings. Ultrasound is as sensitive as intravenous urography and more cost-effective. A plain film of the abdomen should also be obtained, mainly to rule out urinary calculi.
- Cystoscopy: important in younger, as well as in older, patients. One study, looking at almost 2,000 patients with haematuria, found bladder cancer in seven patients aged younger than 40 years.
- 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.
- Other imaging options include retrograde pyelography, multidetector CT urography and MR urography.
If a definite diagnosis cannot be made, investigations should be repeated whenever gross haematuria occurs or after 4-6 months. Occult cancer will usually become evident within one year.
Treatment and management of haematuria
The treatment and management of haematuria depends on the underlying cause.
Further reading and references
Chronic kidney disease: assessment and management; NICE guideline (last updated November 2021)
Perrin P, Bassand X, Benotmane I, et al; Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy. Kidney Int. 2021 Aug100(2):466-468. doi: 10.1016/j.kint.2021.05.022. Epub 2021 Jun 1.
UK National Screening Committee; Evidence map: Screening for bladder cancer, 2020 (downloadable pdf file).
Rees J; Non-visible Haematuria, Primary Care Urology Society, 2017
Benton T et al; Assessment of non-visible haematuria, BMJ Best Practice, 2021
Moreno JA, Martin-Cleary C, Gutierrez E, et al; Haematuria: the forgotten CKD factor? Nephrol Dial Transplant. 2012 Jan27(1):28-34. doi: 10.1093/ndt/gfr749.
Sharp VJ, Barnes KT, Erickson BA; Assessment of asymptomatic microscopic hematuria in adults. Am Fam Physician. 2013 Dec 188(11):747-54.
Yuste C, Gutierrez E, Sevillano AM, et al; Pathogenesis of glomerular haematuria. World J Nephrol. 2015 May 64(2):185-95. doi: 10.5527/wjn.v4.i2.185.
Savige J, Buzza M, Dagher H; Haematuria in asymptomatic individuals. BMJ. 2001 Apr 21322(7292):942-3.
Bolenz C, Schroppel B, Eisenhardt A, et al; The Investigation of Hematuria. Dtsch Arztebl Int. 2018 Nov 30115(48):801-807. doi: 10.3238/arztebl.2018.0801.
Tan WS, Sarpong R, Khetrapal P, et al; Does urinary cytology have a role in haematuria investigations? BJU Int. 2019 Jan123(1):74-81. doi: 10.1111/bju.14459. Epub 2018 Aug 29.
Suspected cancer: recognition and referral; NICE guideline (2015 - last updated December 2021)
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 Feb163(2):524-7.
Moloney F, Murphy KP, Twomey M, et al; Haematuria: an imaging guide. Adv Urol. 20142014:414125. doi: 10.1155/2014/414125. Epub 2014 Jul 17.