Haematuria, management and investigation in Paediatrics

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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, ascities, elevated JVP, pulmonary oedema
  • Hypertension
  • Persistent frank/macroscopic haematuria with no cause identified after baseline investigations 

 

Key points
  1. Haematuria should be confirmed by microscopy to rule out non haematuria causes
  2. The majority of persistent microscopic haematuria is benign and resolves spontaneously 
  3. 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). 
References
  1. Avner ED, Harmon WE, Niaudet P, Nyoshikawa. Pediatric nephrology 6th Ed. 2009 Springer publishers. Volume one. P 477-478
  2. Diven SC, Travis LB. A practical primary care approach to haematuria in children. PediatrNephrol 2000: 14; 65-72
  3. Dodge WF, West EF, Smith EH. Proteinuria and hematuria in schoolchildren: epidemiology and early natural history. J Pediatr 1976; 88:327.
  4. Vehaskari VM, Rapola J, Koskimies O, et al. Microscopic hematuria in school children: epidemiology and clinicopathologic evaluation. J Pediatr 1979; 95:676.
  5. Iitaka K, Igarashi S, Sakai T. Hypocomplementaemia and membranoproliferative glomerulonephritis in school urinary screening in Japan. PediatrNephrol 1994; 8:420.
  6. Wald R. Urinalysis in the diagnosis of renal disease. Curhan GC and Forman JP (Eds). Up to date article. Updated Sept 2016. Accessed November 2016
  7. Mina R, Brunner HI.  Pediatric lupus – are there differences in presentation, genetics, response to therapy and damage accrual compared with adult lupus. Rheum Dis Clin N Am 2010; 36: 53-80 
  8. Bergstein J, Leiser J, Andreoli S. The clinical significance of asymptomatic gross and microscopic hematuria in children. Arch Pediatr Adolesc Med. 2005;159(4):353. 
Editorial Information

Last reviewed: 16 December 2019

Next review: 14 December 2022

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

Version: 4

Approved By: Paediatric & Neonatal Clinical Risk & Effectiveness Committee