2. 128 D.G. Ross
haemoglobin and intact erythrocytes which lyse on the test pad. Free haemoglobin
gives a uniform colour change (orange, green, blue), while intact red blood cells
give a spotted appearance; green spots on yellow/orange background.
Sensitivity=90% in detecting equivalent of >3 RBCs/hpf; specificity=65–80%.
A trace of haematuria should be considered negative, while ³1+ is considered
significant. Non-haemolysed and haemolysed are of equal significance.
Who to Investigate – BAUS Haematuria Guidelines:
1. Single episode of symptomatic nonvisible haematuria (in the absence of UTI or
other transient cause)
2. Persistent (two out of three dipsticks positive) asymptomatic non-visible haema-
turia in patients ³40 years
Significance – 5% of patients will have urological cancer (Table 28.1).
Protein
How? – Based on protein error of indicators principle. Tetrabromophenol blue
changes colour in response to the presence of protein in urine. Sticks are very sensi-
tive, and a trace corresponds to 0.15–0.3 g/L, + to 0.3 g/L, ++ to >1 g/L, +++ to
2.5–5 g/L, and ++++ to >10 g/L proteinuria. Normal urinary protein should be less
than 15 mg/dL or <150 mg/24 h.
Significance – Significant proteinuria is a risk factor for renal disease and cardio-
vascular morbidity and mortality. Patients with persistent proteinuria should have it
quantified using either albumin/creatinine or protein/creatinine ratio. ACR has bet-
ter sensitivity than PCR for low levels of proteinuria. Even microalbuminuria (30–
150 mg/24 h) is significant in diabetic patients. In the context of the definitions of
chronic kidney disease, CKD 1=GFR ³90 mL/min and proteinuria, and CKD
2=GFR 60–89 mL/min and proteinuria. Both groups require monitoring in primary
care. A nephrology referral is indicated if the urinary ACR>70/PCR>100 mg/mmol
or the urinary ACR>30/PCR>50 mg/mmol with microscopic haematuria.
Table 28.1 Diagnoses of patients investigated for microscopic haematuria (Khadra et al. 2000)
Diagnosis % of patients
No cause identified 68.2
UTI 13
Nephrological causes (IgA nephropathy, etc.) 9.4
Bladder cancer 4.8
Stones 4
Prostate cancer 0.3
Kidney cancer 0.2
Upper tract urothelial cancer 0.1
3. 12928 Urinalysis
Leucocytes
How? – Leucocyte esterase is produced by neutrophils which catalyses the hydro-
lysis of either derivatised pyrrole amino acid ester to liberate 3-hydroxy-5-phenol
pyrrole or indoxyl carbonic acid ester to indoxyl. Pyrrole or indoxyl then reacts with
a diazonium salt to produce a purple product.
Significance – The list of potential causes of persistent pyuria is long; however,
the presence of urinary leucocytes is often used as an indicator of UTI along with
dipstick nitrites. Its performance in this setting is shown in Table 28.2.
Nitrites
How? – Nitrite in the urine reacts with r-arsanilic acid to form a diazonium com-
pound which couples with 1,2,3,4-tetrahydrobenzo(h)-quinolin-3-ol to produce a
pink colour.
Significance – Nitrites when present in urine are the result of bacteria reducing
urinary nitrates. Around 60% of Gram-negative bacteria are capable of this, which,
together with the requirement of at least 105
bacteria per milliliter for a positive test,
limits the sensitivity of this test in the clinical detection of UTI (Table 28.2).
pH
How? – Double indicator principle, methyl red and bromothymol blue, which pro-
vides a broad range of colours to cover a urinary pH range of 5–8.5 (visually).
Significance – Urinary pH typically reflects plasma pH. An exception is in renal
tubular acidosis where there is an inability to acidify urine in response to an acid
load. Urinary pH is potentially important in urolithiasis. Uric acid stone formation
requires a pH < 5.5, while the actions of urease-splitting organisms provide the
alkaline environment for struvite lithogenesis. Dietary factors can alter pH; high
protein diets lower pH, while citrate supplements will raise it.
Table 28.2 Utility of leucocyte esterase and nitrite urinalysis in the detection of UTI (St John
et al. 2006)
Dipstick result Pooled sensitivity % Pooled specificity %
LE positive 72 82
Nitrite positive 54 98
LE or nitrite positive 81 77
LE and nitrite positive 43 96
4. 130 D.G. Ross
Glycosuria
How? – Double sequential enzyme reaction:
1. Glucose oxidase catalyses glucose→glyconic acid+hydrogen peroxide.
2. Peroxidasecatalyseshydrogenperoxide+potassiumiodidechromagen→coloured
oxidised chromagen.
Significance – Occurs when blood sugar is >10 mmol/l, the renal threshold.
Potential Errors When Reading a Dipstick
Potential sources of false positive and negative dipstick test results are shown in
Table 28.3.
References
Khadra MH, et al. A prospective analysis of 1,930 patients with hematuria to evaluate current
diagnostic practice. J Urol. 2000;163(2):524–7.
St John A, et al. The use of urinary dipstick tests to exclude urinary tract infection: a systematic
review of the literature. Am J Clin Pathol. 2006;126(3):428–36.
Table 28.3 Sources of false positive and negative urine dipstick results
Test False positive False negative
Haemoglobin Myoglobin Reducing agents:
Bacterial peroxidases 1. Ascorbic acid
Hypochlorite 2. Captopril
Menstruation
Dehydration
Exercise
Protein – Dilute or alkaline urines
Bence-Jones proteins
Leucocytes Formalin Glycosuria (>3 g/dL)
Vaginal discharge Ascorbic acid
Cephalexin
Imipenem
Meropenem
Clavulanic acid
Tetracycline
Nitrites – Non-nitrate-reducing bacteria
Low nitrate diets
Dilute urine
Urine in the bladder for <4 h
Ascorbic acid
Glucose – Ascorbic acid
