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Abstract
‘Urine dipstick’, the commonly used point-of-care test, is an extremely sensitive investigation. Results of this test affected by numerous factors, if not meticulously linked with detailed history and examination, can lead a well-meaning clinician down the wrong clinical pathway. The aim of this article is to provide an overview of this every day test, touching on the physiological and technological basis initially, but mainly focusing on common questions like when to request the dipstick test, the correlation of dipstick results with urine specimen collected by different method and complexities of interpretation of dipstick results in everyday clinical scenarios.
- Urine Dipstick
- Urinary Infection
- Proteinuria
- Haematuria
- Urinalysis
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Introduction
Urinalysis dates back more than 3000 years and originally consisted of checking colour, smell and even taste, and was one of the main investigations physicians used to detect disease.1 In 1850s, chemists detected sugar in urine using a paper test and in 1883, English physiologist George Oliver (1841–1915) marketed ‘Urine Test Papers’. By the 1950s, urine test sticks were made on an industrial scale and marketed commercially. Today, millions of urine tests are performed every day for diagnosing and monitoring a number of conditions.
The urine dipstick is an extremely sensitive test, which is affected by numerous factors. The results, if not correlated with detailed history and examination findings, can lead a well-meaning clinician down the wrong clinical pathway. We aim to give an overview of every day test, touching on the physiological and technological basis initially, but mainly focusing on common questions like when to request the dipstick test, the best method to obtain a reliable sample and how to interpret this simple test in everyday clinical scenarios.
Physiological and technological background
There are a number of test pads in the commonly used urine dipstick to analyse each component of urine, both normal and abnormal. We, clinicians are familiar with interpreting leucocyte and nitrite results in suspected urinary infection, and blood and protein for non-infectious renal diseases. However, are we familiar with the wealth of information the other parameters can give?
Table 1 gives a summary of the physiological and technological features of protein, blood, leucocytes and nitrites dipstick parameters and includes some cautions when interpreting results. Clinical information and interpretation of these important dipstick parameters is highlighted in detail in the manuscript.
Commonly used urine parameters
In table 2, in addition to the details of physiological and technological parameters, brief descriptions of common and uncommon clinical conditions where information from the rest of dipstick results can be applied are highlighted.
Less-commonly used urine parameters
Indications and limitations
Considering the different methods of urine collection in paediatrics and how it affects the dipstick results, is there a gold standard method of urine collection in children?
As paediatricians, we are challenged by a huge variation in our patients, especially with regard to size and weight. Our patient group ranges from premature babies of 23 weeks' gestation weighing <1 kg to 18-year-old young adults who may be weighing 100 kg or more. Naturally, the method of choice for urine collection varies based on age, toilet training and the obvious anatomical gender differences. The chances of false positives are considerable in children, especially in the non-toilet trained child. Methods of urine collection based on age and toilet training status, their reliability and the clinical circumstances of when to use which method are illustrated in table 3. The American Academy of Pediatrics recommends that antibiotics should not be started based on urinalysis from bag urine specimen.5 Samples should ideally be dipstick tested without any delay, but can be stored in a refrigerator or preserved in boric acid-containing containers.
Urine collection methods
In summary, method of choice of urine collection depends on the clinical context, age and gender of the patient and especially if infection is being considered or not?
Should every child attending a paediatric consultation require a urine analysis?
The American Academy of Paediatrics no longer recommends routine urinalysis on children as it gives a low diagnostic yield.5 One study of 2000 asymptomatic patients found abnormal urine dipsticks in 9% of patients, but when repeated only 1.5% showed a persistent abnormality.8 Recent reviews also reveal no evidence that detection and treatment of children with asymptomatic bacteriuria (ASB) prevents subsequent pyelonephritis or scarring.9
In conclusion, currently there is no justification for performing urinalysis as a screening test and it should only be performed if clinically indicated and if results alter the clinical management.
In well-appearing febrile children under 3 years, in whom no other focus of infection can be found, does the presence of solitary leucocytes on a urine dipstick indicate a urine infection that needs treatment?
The leucocyte esterase test detects esterase, which is an enzyme released by leucocytes. Normal children have <10 leucocyte count/µL in midstream urine (MSU), although neonates can have up to 50 leucocyte count/µL.3 All symptomatic urinary tract infections (UTIs) associated with inflammation of the urinary tract should have significant pyuria. Lower amounts of leucocytes, reflected as the absence of leucocyte esterase, are seen in children with ASB. False-positive test results are often found in older girls during any febrile infection and postexercise.2
Urinalysis in asymptomatic children of both genders is generally identical when obtained by gold standard method like suprapubic aspiration. However, in practice there are differences in dipstick parameters, microscopy and colony counts due to varying urine collection methods for different age group children, gender difference and physiological factors like prepuce flushing in infancy and vaginal flushing.
In conclusion, in this specific scenario of fever and no focus, the presence of leucocytes on dipstick does raise the possibility of a urine infection. The diagnosis should only be finalised with the isolation of significant bacterial growth on culture.
Does an isolated positive nitrite test, which indicates bacteriuria, in an asymptomatic child represent a urine infection?
More than 85% of pathogenic bacteria causing UTI in children have the enzymes to convert endogenous nitrates in the urine to nitrites, which are detected by urine dipstick. Some bacteria such as Klebsiella and Enterococcus are non-nitrate reducing. The bacterial conversion from nitrate to nitrite takes 1–4 hours, and therefore the test is not reliable in children, particularly infants, who empty their bladders frequently. False-negative nitrite tests can also occur in ‘low-count’ UTI (<103 colony forming unit of bacteria per mL of urine), dilute urine specimens or acid urine.2 Nitrites do therefore have quite a low sensitivity in detecting a UTI in children (often about 50%) but a very high specificity (approaching 100%).2
ASB is defined as the presence of significant bacterial growth in urine without any overt symptoms. The concern is that these bacterial growths represent subclinical infection, which if left untreated could result in renal scarring. Prevalence of ASB varies with age, sex, race and socioeconomic status. In infants under 3 months, ASB prevalence is estimated to be 1.8% for girls and 0.5% for boys. After infancy, the incidence in males falls to virtually 0% and in preschool girls 0.8%, rising to 1.8% over the age of 6 years.10
For low-risk adult patients, ASB is not thought to be harmful. Although patients are more susceptible to symptomatic UTIs, treatment does not decrease the frequency of symptomatic infection or improve other outcomes such as renal scarring.11 In fact, treatment has led to the selection of resistant organisms and the risk of side effects like Clostridium difficile infection.12
There are some risk factors behavioural patterns specific to the paediatric population, which include atrophy of labia majora, lack of protective hair (easy colonisation of pathogenic bacteria due to impairment of barrier defence) and some behaviour patterns voiding postponement, constipation (urinary stasis), which can contribute to proliferation of bacteriuria leading to UTI. These are illustrated in box 1.
Physical and behavioural risk factors for urinary tract infection (UTI)
Physical
Uncircumcised males: uncircumcised males <3 months have a much higher prevalence of UTI than circumcised males of the same age.13
Male: physiological phimosis in males results in ballooning of the prepuce, stasis of residual urine in the prepuce, irritation and inflammation of the urethral meatus.
Female: shorter urethra, poor hygiene, lack of protective hair and atrophy of labia majora due to lack of oestrogen in prepubertal females, labial adhesions.
Behavioural
Voiding postponement: voiding interval needs to be <3 hours in school-age children or incomplete pelvic floor relaxation occurs and therefore incomplete bladder emptying.
Constipation: the over distended rectum affects bladder sensitivity and contractility.
Poor fluid intake.
In this clinical scenario, the presence of isolated positive nitrites only represents bacteriuria and per the National Institute for Health and Care Excellence (NICE) guidelines, asymptomatic bacteria should not be treated.7
There are a number of localised perineal conditions that can give positive urine dipstick results and can mimic UTI (box 2). Therefore, thorough history including use of bubble baths and reports of vaginal discharge should be taken. An external examination including the perineum is essential to rule out these conditions.
What does isolated proteinuria on a urine dipstick indicate? What are your management considerations?
The importance of proteinuria is very different in different clinical scenarios. Proteinuria in the acutely unwell child should be correlated to the overall clinical presentation including oedema, macroscopic or microscopic haematuria, raised blood pressure and impaired kidney function.
There are many benign causes for proteinuria. They include
fever
exercise
contamination with vaginal secretions
orthostatic proteinuria
None of these signifies an important clinical condition but need further evaluation to ensure the transient nature of the abnormality and ensure long-term follow-up of children with chronic kidney disease.
In conclusion, transient proteinuria is generally considered to be due to benign or non-renal causes. It is important to repeat the test or consider a formal quantification of the proteinuria using timed urine collection or protein/creatine ratio to confirm the transient nature of the proteinuria.
Should your approach to proteinuria change if the child is known to have chronic kidney disease?
Children with impaired glomerular filtration generally have fixed proteinuria of varying degree. Significant fixed proteinuria, which is mostly albuminuria as highlighted in table 1, is due to glomerular impairment will need appropriate renal work up. Some of the common renal conditions causing proteinuria and their investigations before considering renal biopsy are given in table 4. This is partly due to hyperfiltration of remaining glomeruli in a damaged kidney.
Causes and investigations of fixed proteinuria in children
In a child known to have chronic kidney disease, degree of proteinuria is related to the long-term prognosis with increasing amounts of proteinuria indicating faster progression to end-stage renal failure. These children need regular renal follow-up and are typically treated with an ACE inhibitor or an angiotensin II receptor blocker to reduce their proteinuria and slow down their progression to end-stage kidney disease.
In a child with isolated haematuria on urine dipstick, could this indicate renal disease?
The urine strip detects blood by the peroxidase-like action of both haemoglobin and myoglobin. Hence, the blood reagent on urine dipstick can be positive in the presence of red blood cells, free haemoglobin and myoglobin in the urine.
Clinical considerations include the presence of dysuria, fever and flank or abdominal pain, and clinical findings of microscopic or macroscopic haematuria, hypertension, oedema, rash and proteinuria. Further evaluation of haematuria should commence with confirming the presence of red blood cells by direct microscopy. The long-term management depends on whether haematuria is microscopic or macroscopic, persistent or intermittent associated with proteinuria, which in turn needs to be differentiated from the benign causes. Box 3 gives an outline of the causes of haematuria.
Common causes of chronic haematuria
Causes of microscopic/macroscopic haematuria
Calculi
IgA nephropathy
Alport's disease
Sickle cell disease
Schistosomiasis
Haemorrhagic cystitis
Renal tumours
A child with symptoms and signs of an acute renal disease should be investigated further
for a glomerulonephritis (see under proteinuria)
for haemorrhagic cystitis with urine microscopy and culture
for a calculi or malformation with ultrasound of the urinary tract (and plain abdominal X-ray in case of suspicion of renal calculi)
In conclusion, children with persistent microscopic haematuria, in the absence of proteinuria, with normal serum creatine and normal renal ultrasound and without history of any renal disease in the family do not generally need invasive investigations such as renal biopsy. However, these children should be monitored yearly considering the increased risk of end-stage renal failure in this group.15
Topics for further research
Further studies are required to have a better understanding of sensitivity and specificity urinary leucocytes and/or nitrite test to include or exclude the diagnosis of UTI in different age groups. There is considerable research using molecular biology techniques to identify and quantify bacterial colonies to reduce the time taken by the gold standard method of urine culture.16 In future, bedside confirmation of urinary infection and identification of the causative organisms might be possible if the new methodology as described by Lehman et al can be incorporated into the current urine dipstick parameters.17 From a wider context, urine dipstick tests for colon cancer, coeliac disease, prostate cancer, ulcerative colitis, pneumonia and organ transplant rejection are being developed.1
Clinical bottom line
Clinicians should request a urine dipstick analysis only if clinically indicated. As per the recent NICE guidelines, urinalysis is advised in children with clinical signs of UTI and/or unexplained fever over 38°C for 24 hours.7 Medical and nursing staff should be educated to stop testing urine samples on every child who passes through the paediatric doors.
Considering the high specificity and negative predictive value of the urine dipstick, UTI can be effectively ruled out, in at least all children outside infancy, if the dipstick is completely negative for leucocytes and nitrites regardless of the urine collection method.
UTI as a diagnosis should only be considered when there is a combination of positive clinical history, abnormal urine dipstick results (ideally which are reproducible) accumulated by a reliable collection method and lack of signs or symptoms of alternative diagnoses. UTI should only be confirmed by a positive culture of uropathogenic bacterial growth with adequate colony count for the method of collection of urine sample.
In older children with no symptoms or with non-specific symptoms who have positive urine dipstick results, a provisional diagnosis of ASB should be strongly suspected and the sample should be sent to the lab without embarking on empiric antibiotic treatment. Further enquiry about dysfunctional voiding habits, bowel movement pattern, drinking habits and a thorough clinical examination including the perineal area is highly likely to give further valuable clinical information towards the final diagnosis and long-term prevention.
Apart from diagnosing and ruling out urinary infection, the other parameters provide valuable information about number of non-infectious, but significant renal and metabolic diseases. Giving attention to less heeded parameters may give valuable pointers to changes in the homeostasis of bodily functions and occasionally clues to rare, but significant clinical disease processes.
Test your knowledge
A negative nitrite result can be due to
Urinary frequency
Elevated specific gravity
Oxidising drugs
Vitamin C
Glycosuria
Causes of transient proteinuria and false-positive proteinuria include
Fever
Concentrated urine
Alkaline urine
Phenazopyridine
Exercise
Causes of sterile pyuria include
Chlamydia
Fever
Tuberculosis
Kawasaki disease
Appendicitis
Urethritis
Bladder tumours
Foreign bodies
Exercise
Corticosteroids
Alkaline urine is associated with the following renal calculi
Calcium carbonate
Calcium phosphate
Xanthine
Cysteine
Calcium oxalate
Uric acid
Magnesium phosphate
Spot the odd one/ones out—which of these foods will not affect urine colour
Beetroot
Carrot
Rhubarb
Blackberries
Spinach
Cherries
The answers are after the references.
Acknowledgments
The authors thank Dr Dean Lethaby, Mr Ciaran Cyriac and Miss Lisbeth Cyriac for proof reading and correcting the manuscript.
Appendix
Answers to the multiple choice questions
All of the above
All of the above
All of the above
A, B, G
E, F
References
Footnotes
Contributors KH: Formulated the first draft of the article and did further revisions. KT: Specialist advice and revision of the article. JC: The conception, design, revision and the overall responsibility of the article.
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.