Microscopic Haematuria

Microscopic (non-visible) haematuria is the presence of red blood cells in urine that are detected only by dipstick or microscopy: 3 or more red cells/HPF on microscopy of a centrifuged specimen, or 1+ or more on a dipstick that is confirmed by microscopy. Dipstick positive but microscopy negative suggests haemoglobinuria, myoglobinuria or a false positive.

It arises from the glomerulus, tubulointerstitium, collecting system, ureter, bladder, prostate or urethra. The most important distinction is glomerular from non-glomerular, as the second group includes urological malignancy.

Glomerular causes: IgA nephropathy, thin basement membrane disease, Alport syndrome (collagen IV disease), post-infectious glomerulonephritis, lupus nephritis, membranoproliferative disease and vasculitis.

Non-glomerular causes: urinary tract infection, calculi, bladder cancer, renal cell carcinoma, upper tract urothelial cancer, benign prostatic hyperplasia, polycystic kidney disease, medullary sponge kidney, papillary necrosis, schistosomiasis (endemic in parts of Africa), sickle cell trait or disease, renal tuberculosis, trauma and anticoagulation (which unmasks, but does not by itself explain, haematuria).

Benign transient haematuria follows vigorous exercise, menstruation contamination, sexual activity and fever.

Most patients are asymptomatic, with haematuria found on screening.

• Glomerular: hypertension, oedema, proteinuria, family history of kidney disease or deafness (Alport), preceding sore throat (IgA nephropathy)
• Non-glomerular: dysuria, frequency, loin pain with colic, lower urinary tract symptoms, weight loss, smoking, occupational exposure to dyes, rubber or aromatic amines, history of pelvic radiotherapy or cyclophosphamide
• Endemic exposure: swimming in fresh water in schistosomiasis endemic areas

Red flags: age 45 or over, smoking history, visible haematuria in the past, associated proteinuria (albumin:creatinine ratio above 30 mg/mmol), eGFR below 60, hypertension, systemic features, family history of renal cancer or kidney failure.

• Repeat dipstick on two further samples; persistent if 2 of 3 are positive. Exclude urinary tract infection first and recheck 4 to 6 weeks after treatment.
• Urine microscopy: dysmorphic red cells (more than 5% acanthocytes) or red cell casts mean glomerular origin; isomorphic cells mean non-glomerular origin.
• Blood tests: creatinine, eGFR, urine albumin:creatinine ratio, blood pressure. If proteinuria or reduced eGFR: C3, C4, antinuclear antibody, ANCA, hepatitis B and C, HIV.
• Haemoglobin electrophoresis in people of African ancestry.
• Urine for schistosome eggs (terminal urine, midday collection) in endemic exposure.
• Imaging: renal tract ultrasound, then CT urogram for risk stratified patients.
• Flexible cystoscopy for adults aged 45 or over, or younger with risk factors (smoking, occupational exposure, recurrent infection, irradiation).
• Kidney biopsy when glomerular origin is combined with proteinuria above 100 mg/mmol, impaired eGFR or systemic disease. Isolated glomerular haematuria with normal eGFR and no proteinuria is often a thin basement membrane or early IgA disease; biopsy is not usually needed.

Differentials: contamination, haemoglobinuria, myoglobinuria, porphyria, beeturia, drugs (rifampicin, nitrofurantoin), pseudohaematuria.

Source directed treatment

• Urinary tract infection: treat with nitrofurantoin 100 mg modified release twice daily for 3 days (eGFR at least 45), or trimethoprim 200 mg twice daily for 3 days where susceptible; confirm resolution.
• Stones: analgesia (diclofenac 50 mg three times daily if eGFR permits), tamsulosin 400 microg daily for ureteric stones up to 10 mm, urological intervention for obstruction.
• Schistosomiasis: praziquantel 40 mg/kg orally as a single dose (or 20 mg/kg twice in one day).
• Bladder or renal malignancy: urgent urological referral.
• IgA nephropathy: ACE inhibitor if proteinuria above 0.5 g daily; a 3 to 6 month period of supportive care is the first approach.

Follow up for negative investigations. Annual blood pressure, urinalysis, creatinine and albumin:creatinine ratio for at least 3 years, with re-referral for visible haematuria, new proteinuria, falling eGFR or new urinary symptoms.

Refer to nephrology for glomerular haematuria with eGFR below 60, albumin:creatinine ratio above 30 mg/mmol, or new hypertension.

Refer to urology for age 45 or over, risk factors, or any visible haematuria.

Special groups

• Children: glomerular causes dominate; check family history, hearing and eyes for Alport syndrome.
• Anticoagulated patients require the same evaluation; anticoagulation does not explain haematuria.
• Pregnancy: haematuria with proteinuria or hypertension needs assessment for pre-eclampsia.