Haematuria, management and investigation in Paediatrics (145)

Objectives

1. To define microscopic and macroscopic haematuria
2. To understand the non haematuria causes for discoloured urine
3. An overview of the causes of microscopic and macroscopic haematuria, their clinical features and investigation
4. Red flags to look for in patients with haematuria

Scope

Children presenting with haematuria.

Audience

The following guideline has been developed in conjunction with clinicians based at the Renal Unit at the Royal Hospital for Children, in Glasgow. They are based on current evidence and best practice relating to the management and investigation of haematuria. They are for the use of any clinicians caring for children with haematuria, including general paediatricians, GPs and other specialists.

This clinical guideline adheres to the principles outlined in the criteria in the AGREE (Appraisal of Guidelines, Research and Evaluation for Europe) guideline appraisal instrument and the NHSGGC Clinical Guideline Framework.

Definition

Microscopic haematuria is the presence of five red blood cells/mm3 in uncentrifuged urine (1) or 5 red blood cells per high powered field (2). Persistent microscopic haematuria is three samples with this number of RBC’s taken at least a week apart, not after exercise. There is no published data detailing the amount of RBCs seen on microscopy for each dipstick result 0, trace, 1+, 2+, 3+, however 2+ or greater on repeated is regarded as significant.

Population studies of school aged children suggest that about 1% have two or more dipsticks positive for microscopic haematuria, but this only persists at six months in a third (3-5).

Macroscopic haematuria is where the urine is visibly discoloured. As little as 1 mL of blood per litre of urine can produce a visible change in the urine colour (6).

Blood that is glomerular in origin can be cola coloured, due to longer contact with the acidic urine causing the haem pigment to be oxidized to a methaem derivative (1). Dysmorphic red blood cells and acanthocytes can be seen on microscopy
Lower urinary tract blood will be red or pink coloured and may be at the beginning or end of micturition.

Table 1: Non haematuria causes for red or brown urine

Substance	Cause	Urine Dipstick
Haemoglobin	Haemolysis	Positive
Myoglobin	Rhabdomyolysis	Positive
Food	Beetroot, food dyes, berries containing anthocyanins like blueberries or raspberries	Negative
Drugs	Metronidazole, nitrofurantoin, doxorubicin, rifampicin	Negative
Inborn errors of metabolism	Porphyria, tyrosinaemia	Negative
Urate Crystals	Concentrated urine in neonates	Negative

Reproduced from 15 minute consultation on microscopic haematuria in children article

Table 2: Causes of both microscopic and macroscopic haematuria

Aetiology	Relevant history and examination	Investigations
Urinary tract infection	Depends on ag; dysuria, frequency, fever, vomiting, off feeds	Urine dipstick Urine microscopy, culture and sensitivity
Irritation to the meatus or perineum	History and examination	Nil
Adenovirus haemorrhagic cystitis	Symptoms of upper respiratory tract infection (URTI) with episodes of haematuria	Respiratory viral screen including adenovirus
Tumour (Wilms)	Asymptomatic abdominal mass (commonly), abdominal pain, hypertension, fever. Associated with overgrowth syndromes, Bloom's syndrome, Denys-Drash syndrome or WAGR	USS abdomen
Nephrolithiasis	Renal colic may be absent, dysuria, incidental finding on imaging, passage of stones	USS abdomen then abdominal xray as first line investigations
Glomerulonephritis including post infectious GN, HSP GN, membranoproliferative GN	History of cola coloured urine, odema, oliguria, hypertension, proteinuria, impaired renal function. Haematuria onset 7-10 days post URIT in postinfectious GN. Rash and joint swelling/pain in HSP.	ASOT, antiDS DNA, throat swab, U&E, FBC, C3,C4, IgGs, ANCA (see glomerulonephritis protocol)
IgA nephropathy	Haematuria onset 1-3 days after URTI in Ig A nephropathy	High serum IgA may be suggestive, but no definitive test other than biopsy
Focal segmental glomerulosclerosis (FSGS)	FSGS usually presents with proteinuria that may become nephrotic range	Urine PCR
Alport syndrome (COL4A5, COL4A3, COL4A4 mutations)	Persistent microscopic haematuria +/- macroscopic haematuria. There may be proteinuria, renal impairment, deafness, ophthalmological abnormalities	Genetic testing (discuss with genetics or nephrology)
Sickle cell trait/disease	Family history. Due to haemoglobin S polymerization and erythrocyte sickling within the renal medulla (7).	Hb electrophoresis
Clotting abnormalities	Relevant history and family history, petechiae, bruising	FBC and clotting as initial steps
Trauma	Relevant history and examination. Note, undiagnosed structural can be diagnosed if bleeding occurs with only mild trauma	May need USS
Exercise	Microscopic and macroscopic haematuria can be seen with vigorous exercise	Nil
Haemolytic uraemic syndrome	Bloody diarrhoea, oliguria, history of infectious contact, pallor.	Stool culture, U&E, FBC

GN, Glomerulonephritis; ASOT, antistreptolysin O titre; U&E, urea and electrolytes; FBC, full blood count; USS, ultrasound; Hb, haemoglobin; HSP, henoch schonlein purpura; FSGS, focal segmental glomerulosclerosis; PCR, protein creatinine ratio.

Table 3: Microscopic haematuria only

Aetiology	Relevant history and examination	Investigations
Thin basement membrane disease (COL4A3, COL4A4) also called ‘benign recurrent haematuria’	Persistent or intermittent microscopic haematuria, benign. Thought of as ‘carrier’ form of Alport syndrome.	Nil required
Structural abnormalities e.g. horseshoe kidneys	Asymptomatic, abdominal pain, UTIs	USS kidneys, ureters, bladder
Hypercalciurea	Many causes, hypercalcicurea may be present with or without hypercalcaemia	Urine calcium/creatinine ratio
Drug or toxin ingestion	Aspirin, sulphonamide, lead, tin, amitriptyline, chlorpromazine, ritonavir, carbon monoxide, mushrooms, phenol (7). See toxbase for management	Urine drug screen

The majority of patients with microscopic haematuria have a benign cause that resolves spontaneously. In symptomatic patient, the symptoms may give a clue to the diagnosis. In a study of 228 patients with asymptomatic macroscopic haematuria, 36% had no cause identified, 22% had hypercalciuria, 16% had IgA nephropathy, 7% had post streptococcal glomerulonephritis, 2% had other glomerulopathies including thin TBM disease, 2% had congenital anomalies, 1% had sickle cell trait (8).

Investigations

Microscopic haematuria only

Isolated microscopic haematuria is common and only requires investigation if persistent.

Investigate for specific pathologies as per clinical features; ensure that patient has blood pressure measured. In patients with asymptomatic persistent haematuria:

Urine microscopy
Urine calcium/creatinine ratio
Dipstick testing of the immediate family

If microscopic haematuria is still present 6 months later, consider checking U&E, FBC and ultrasound kidney, ureters and bladder.

Macroscopic haematuria

Investigate for specific pathologies as per clinical features; ensure that patient has blood pressure measured. If asymptomatic;

Urine microscopy for presence of RBCs
Urine culture
Urine protein creatinine ratio
U&E, FBC, clotting, LFTs
Urine calcium/creatinine ratio
Renal USS
Urine analysis of family members

Box 1: Red flag features

What are the red flag features to look out for? Consider discussion with nephrologist

Abnormal renal function
Proteinuria 2+ or more on the dipstick, please send a urine protein/creatinine ratio
Signs of fluid overload: peripheral oedema, ascites, elevated JVP, pulmonary oedema
Hypertension
Persistent frank/macroscopic haematuria with no cause identified after baseline investigations

Key points

Haematuria should be confirmed by microscopy to rule out non haematuria causes
The majority of persistent microscopic haematuria is benign and resolves spontaneously
Red flag symptoms include; persistent frank haematuria, hypertension, abnormal renal function, proteinuria and signs of overload. Patients with these features should be discussed with a nephrologist (after baseline investigations).

Last reviewed: 16/12/2019

Next review date: 31/10/2025

Author(s): Dr Rebecca Dalrymple, Paediatric Registrar & Dr Ian Ramage, Consultant Paediatric Nephrologist.

Version: 4

Approved By: Paediatric & Neonatal Clinical Risk & Effectiveness Committee

References

Avner ED, Harmon WE, Niaudet P, Nyoshikawa. Pediatric nephrology 6^th Ed. 2009 Springer publishers. Volume one. P 477-478
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Vehaskari VM, Rapola J, Koskimies O, et al. Microscopic hematuria in school children: epidemiology and clinicopathologic evaluation. J Pediatr 1979; 95:676.
Iitaka K, Igarashi S, Sakai T. Hypocomplementaemia and membranoproliferative glomerulonephritis in school urinary screening in Japan. PediatrNephrol 1994; 8:420.
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