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Approach to a child with haematuria

Shivaram Hegde and Rajesh Krishnan
Department of Paediatric Nephrology, Children’s Kidney Centre, University Hospital of Wales, Cardiff
Haematuria is an important sign of renal tract disorders and affected patients should undergo detailed evaluation. Appropriate investigations are essential, particularly in those with macroscopic haematuria, symptomatic microscopic haematuria and in those with associated proteinuria to identify the cause. Patients needing referral to specialised services should be identified early.
Haematuria (presence of an abnormal quantity of red blood cells in the urine) is a common reason for referral to nephrologists. While it is an important sign of urinary tract and renal disease but proteinuria often is a more important diagnostic and prognostic finding. Haematuria can be gross (i.e. the urine is overtly bloody, smoky, or tea coloured) or microscopic. Healthy children can have occasional red cells in the urine but (persistent) microscopic haematuria is considered significant if there are > 5 red cells/high power field in at least three fresh samples collected minimum 1 week apart.1 Haematuria can be symptomatic or asymptomatic, transient or persistent, and either isolated or associated with other urinary abnormalities like proteinuria.
Gross or macroscopic haematuria (MaH) is alarming to the patient/parents and deserves a prompt, thorough investigation to determine its cause. It can result from as little as 1 ml of blood in 1 litre of urine, and therefore the colour does not reflect the degree of blood loss. The degree of haematuria bears no relationship to the seriousness of the underlying cause. It may be initial (a symptom of urethral cause); total/complete (due to kidney or diffuse bladder pathology) or terminal (occurring at the end of the urine stream, in prostatic, trigonal or posterior urethral disorders). Many substances other than red blood cells (RBCs) can cause the urine to become red in colour (Table 1) which needs to be distinguished.

Table 1 Red urine without haematuria (false positive tests) 
Microscopic haematuria (MiH), seen more often than gross haematuria may be discovered as an incidental finding on a routine urinalysis or by urinalysis prompted by urinary or other symptoms. Urine dipsticks are used routinely for detection of haematuria because of their relatively high sensitivity. It uses peroxidise-like colour changing chemical reaction between
haemoglobin (and myoglobin) and a chemical indicator (tetramethylbenzidine) impregnated on the dipstick. Dipstick is more sensitive for free haemoglobin than for RBC.
In general, children with isolated asymptomatic microscopic haematuria tend to do well.1 Nevertheless, persistent microscopic haematuria deserves an evaluation as to its cause.
Causes of haematuria
Amongst various causes of haematuria2,3 most are benign, particularly those with isolated asymptomatic microscopic haematuria.1 However it is important to differentiate benign forms of haematuria from those due to significant underlying renal disease.
Table 2 Common causes of haematuria 
The pathophysiology of haematuria depends on the anatomic location of bleeding in the urinary tract. A distinction has conventionally been drawn between glomerular and extraglomerular bleeding, separating nephrologic and urologic disease (Table 3).
Glomerular haematuria indicates blood originating from nephron. Various inherited or acquired disorders affecting the structure and integrity of the glomerular capillary wall lead to disruption of the filtration barrier in the glomerulus. Red blood cells (RBCs) can enter the urinary space from these glomeruli or rarely from the renal tubule. Some of these RBCs can be trapped in tubular mucoprotein and will appear in the urine as RBC casts, an important finding in various glomerulonephritis. However casts can be absent and isolated RBCs may be the only finding in some nephron disorders. These RBCs exhibit typical morphological changes as a consequence of being distorted via passage through the abnormal glomerular structure and are called dysmorphic (deformed or acanthocytic) RBCs. The presence of proteinuria also suggests a glomerular source of bleeding.
Bleeding from upper or lower collecting system is called extraglomerular haematuria. Anything that disrupts the uroepithelium, such as irritation, inflammation, or invasion, can result in normal appearing (eumorphic- uniform size and shape) RBCs in urine without any casts.
Haematuria without proteinuria or casts is termed isolated haematuria. Although a few glomerular diseases may produce isolated haematuria, this finding is more consistent with extraglomerular bleeding.
Table 3 Differentiating glomerular from non-glomerular haematuria

Approach to a child with haematuria
The main goals in management of a child with haematuria are to:
1. Establish the presence of true haematuria
2. Do detailed clinical evaluation- careful history and examination to identify common causes
3. Perform appropriate investigations and to treat common causes. Also identify patients who need referral to nephrologist or urologist for further assessment or treatment

1. Establish the presence of true haematuria
Confirmation of the presence of haematuria is an important step as there are various causes for false positive and false negative results (Table 1). The presence of hematuria is easily established in patients with macroscopic bleeding but bewares of other causes of red urine (Table 1). On centrifugation of the urine specimen the sediment is red in haematuria whereas the supernatant is red in other common causes of red urine (Fig 1).
In patients with microscopic haematuria make sure it is confirmed on at least three samples (see definition) which helps to exclude transient MiH associated with intercurrent febrile illnesses .Positive urine dipstick does not confirm haematuria as positive results are also seen in haemoglobinuria and myoglobinuria. This confirmation requires a microscopic examination of the urine for the presence of RBCs (meaning true haematuria). If no RBCs are found on microscopy, the possibility of false negative tests (conditions leading to lyses of the RBCs) should also be kept in mind (Table 1).
Morphologic study of urinary RBCs (dysmorphic or eumorphic) with a phase-contrast microscope might be helpful in distinguishing glomerular from non-glomerular bleeding.
2. Clinical evaluation
A detailed and precise history and examination together with urinalysis provide vital information to determine the level of haematuria (upper versus lower urinary tract) and urgency of evaluation4.
Enquire about symptoms of specific conditions causing haematuria (Table 1). Common presenting symptoms of these disorders include recent history of upper respiratory tract or gastrointestinal (bloody diarrhoea) infections, passing cola coloured urine, oliguria, facial/body oedema, hypertension, skin rashes, joint pain/swelling, loin pain, renal colic, UTI symptoms,
flank mass and symptoms of severe hypertension. Various genetic renal diseases should be kept in mind and careful documentation of family history (of haematuria, renal failure, arthritis and deafness) is essential.
Physical examination should uncover evidences of underlying illnesses. Hypertension, oedema, hepatomegaly, raised jugular venous pressure and other signs of cardiac decompensation might suggest nephritis. Dysmorphic features (suggesting syndromic conditions), abdominal masses and abnormalities of spine, external genitalia, skin and nervous system should be looked for.
3. Investigation, treatment and identification of patients needing referral
Table 4 lists the investigations performed in selected group of patients with haematuria. A stepwise approach to children with MaH and MiH has been suggested in Fig 1 and 2. If common causes (e.g. UTI) are found they should be treated and followed up locally. Well children with isolated MiH are unlikely to have significant pathology and tend to do well. But they do need follow up to ensure it resolves and parents should be reassured. In general referral (sooner for MaH) to a nephrologist is recommended for children with nephritis, renal impairment, hypertension, stones, nephrocalcinosis, family history of significant renal disease or persistent haematuria of unknown cause. Significant underlying renal disease is more likely in this group of patients and timely referral is essential.
Fig 1 Approach to a child with macroscopic haematuria

* On centrifugation of the sample
# by phase contrast microscopy
@ Lactate dehydrogenae with other signs of haemolysis
$ Creatinine phosphokinase
Table 4 Investigations in selected patients with haematuria
Fig 2 Approach to a child with microscopic haematuria (MiH)   
Haematuria, gross or microscopic, is an important sign of renal and urinary tract disorders and affected patients should undergo careful evaluation once it is confirmed. Appropriate detailed investigations are essential to identify the cause in selected patients, particularly those in whom the haematuria is macroscopic, symptomatic or is with associated proteinuria, renal impairment or hypertension. Children with isolated asymptomatic microscopic haematuria tend to do well. Patients needing referral to specialised services should be identified early.

1. Dodge W.F., West E.F., Smith E.H. & Bunce H. (1976) Proteinuria and haematuria in schoolchildren: epidemiology and early natural history. J Pediatr, 88, 327–347.
2. Feld L.G., Waz, WR, Perez, LM, Joseph, DB. (1997) Haematuria. An integrated medical and surgical approach. Pediatr Clin North Am, 44, 1191-1210.
3. Milford D.V., & Robson A.M. (2003) Haematuria. In Webb NJA, Postlethwaite RJ (eds), Clinical paediatric nephrology, 3rd edn Oxford, Oxford Medical Publications, 4-9.
4. Davis I.D. & Avner E.D. (2007) Clinical evaluation of the child with haematuria. In Kliegman R.M., Behrman R.E., Jensen H.B. & Stanton B.F. (eds), Nelson’s textbook of
paediatrics, 18th edn. Vol 2 Philadelphia, Saunders, 2168- 2170.

Page Reference: 
Welsh Paed J 2009;31:7-9