Is There a Problem?

Gross haematuria may be detected when red blood cell (RBC) content exceeds 2500/µl of urine or about 150 RBCs per high-power field (HPF) on microscopic examination. Microscopic haematuria may be detected by urine dipstick at 100 RBCs/µl and small amounts are normal with cystocentesis. Signs such as dysuria, stranguria, periuria or pollakiuria support an abnormality. Isolated microscopic haematuria should be repeatable before embarking on investigation.

Differential Diagnoses

Haematuria should be differentiated from haemoglobinuria (usually resulting from haemolysis within the vascular space) and myoglobinuria. Samples should be centrifuged at 1500-3000 rpm for 5 minutes. True haematuria will result in a pellet of red blood cells at the bottom of the centrifuged tube with a clear supernatant, whereas with haemoglobinaemia the urine will remain discoloured diffusely red/pink. If haemoglobinuria is suspected the supernatant of a similarly spun whole blood sample should be examined for haemolysis. Myoglobinuria usually results from marked muscle trauma or feline aortic thromboembolism. The urine tends to be more browny-red discoloured, does not separate with centrifugation and plasma is not grossly discoloured. Discoloured urine is seen after administration of haemoglobin-containing oxygen-carrying solutions. Potential causes of haematuria are shown in Figure 1.

Figure 1. Causes of haematuria in dogs and cats.

 Haemorrhage due to coagulopathy (site may be anywhere in urinary tract):

 Disorders of primary haemostasis (e.g., thrombocytopenia)

 Disorders of secondary haemostasis (e.g., haemophilia, disseminated intravascular coagulation (DIC), vitamin K antagonism)

 Upper urinary tract haemorrhage:

 Kidneys:

 Trauma (blunt, penetrating, renal biopsy)

 Intoxication (especially ethylene glycol, aminoglycosides)

 Infection (Leptospirosis, Borreliosis, pyelonephritis)

 Nephrolithiasis

 Neoplasia

 Polycystic kidney disease

 Glomerulopathies

 Idiopathic renal haematuria

 Vascular malformation, infarction

 Ureters:

 Trauma

 Neoplasia

 Ureterolithiasis

 Lower urinary tract haemorrhage:

 Bladder:

 Trauma

 Infectious cystitis:

 Bacterial

 Fungal (e.g., Candida spp.)

 Parasitic (e.g., Capillaria plica)

 Urolithiasis

 Neoplasia

 Polypoid cystitis

 Feline idiopathic cystitis

 Cyclophosphamide-induced haemorrhagic cystitis

 Urethra:

 Trauma

 Urolithiasis

 Neoplasia

 Urethritis

 Genital tract:

 Trauma

 Prostatic disease (benign prostatic hyperplasia, prostatitis, neoplasia)

 Oestrus

 Endometritis/pyometra

 Vaginal/uterine neoplasia

 Vaginitis

 Superficial lesions of external genital tract e.g., preputial lacerations, encircling preputial hair, foreign body, urethral prolapse

History

The history should include environmental, dietary and vaccination history, access to toxins (especially rodenticides), review of prior medical history/long-term medications and the health status of in-contact animals and reproductive history in females. Description of urinating is important: stranguria and pollakiuria may suggest lower urinary tract discomfort and should focus attention on this region, though blood clots or uroliths moving from the upper urinary tract should also be considered. The timing of gross haematuria has been suggested to help with localising the source but caution is urged in over-reliance on timing as a diagnostic tool. Periuria should be distinguished from urine marking. It is important to establish whether signs of systemic illness such as weight loss, which may suggest a systemic disease, renal disease or neoplasia, are present or whether owners have noted polyuria/ polydipsia (as distinct from pollakiuria), which suggests upper urinary tract involvement. Accompanying dyschezia may suggest pelvic cavity obstructive disease such as prostatomegaly. Other body systems should be verbally assessed, even if they do not seem immediately pertinent.

Physical Examination

A complete physical examination including hydration status, presence of signs of systemic illness, body condition and evidence of bleeding elsewhere (e.g., petechiation, ecchymoses, haematomata) should be evaluated prior to specific urogenital examination. Signs of trauma, particularly in free-ranging cats, should be examined. Both kidneys, where possible, should be palpated for size, shape, symmetry, smoothness, presence of pain and firmness. Bladder palpation should be interpreted cautiously; interpretation of 'bladder wall thickness' will depend on degree of distension. The perirenal abdomen and pelvis (for mass lesions and focal/diffuse pain) should be palpated. Examination of the external genitalia, including retraction of the prepuce in males, visual inspection of the vulva in females and a per-vaginum examination in female dogs, is mandatory in all cases of haematuria. Rectal examination and digital evaluation of the prostate and of the intrapelvic urethra should be performed in all dogs.

Routine Laboratory Tests

Anaemia may be seen with prolonged/massive haematuria, and thrombocytopenia may indicate that haematuria is due to a primary haemostatic defect. Disorders of secondary haemostasis are evaluated by a coagulation panel. Presence or absence of an inflammatory leucogram neither justifies nor excludes a diagnosis of urinary tract infection. Polycythaemia may be seen with inappropriate erythropoietin production due to renal tumours.

Azotaemia (interpreted with urine S.G.) indicates diminished glomerular filtration rate. Hypoalbuminaemia may be identified in patients with prolonged/massive renal protein loss.

Urinalysis

This should be performed in any dog or cat with haematuria and should be collected by cystocentesis when microbiological information is required. Samples should be assessed for colour, turbidity, specific gravity, chemical and cytological evaluation and culture.

A fresh wet-mounted slide and centrifuged sediment preparation, stained with 'Diff-Quik' (or similar) can yield much information. Microorganisms such as bacteria, yeasts or parasitic ova (e.g., Capillaria plica) may be apparent though care should be taken not to over interpret debris, stain precipitate or Brownian motion as evidence of bacteriuria. Cytological bacteriuria is seen when there are >10,000 organisms/ml rods and >100,000 organisms/ml cocci. Urine culture is generally more sensitive with >10³ colony-forming units (CFUs) per ml being significant for cystocentesis samples, >10⁴ CFU/ml for catheter samples, >10⁵ CFU/ml for mid-stream samples. Presence of large numbers of tubular casts (>2/HPF) or numerous renal tubular epithelial cells indicate renal disease, though the former are easily disrupted during sampling. Clumps of transitional epithelial cells displaying cytological criteria of malignancy may indicate transitional cell carcinoma. Crystalluria is interpreted cautiously, remembering that it merely indicates that urine is supersaturated with chemical components enough to support crystal growth; it is not synonymous with urolithiasis. Many crystal types will precipitate in urine with time and refrigeration.

Diagnostic Imaging

Radiography and ultrasonography give complementary information. Patients must be properly prepared for contrast procedures by prior administration of cleansing enemas.

Upper Urinary Tract

Ultrasonography of the kidneys is useful but there is much anatomical variation and caution is urged to avoid over-interpretation and to adopt a systematic approach. Size, shape and echogenicity are assessed, and cortex, medulla and pelvic regions evaluated. The ureters cannot normally be visualised except at their beginning and termination in the bladder trigone and where ureteral obstruction or ureterocele exists. Changes consistent with neoplasia, abscessation, infarction, nephritis, cortical infiltrative diseases, polycystic kidneys, perinephric pseudocysts, renal dysplasia, pyelonephritis and nephrolithiasis may be appreciated. Plain lateral and ventrodorsal (VD) radiographs of the kidneys may show abnormalities in size, shape, position and number but do not show internal detail. It is essential to thoroughly evaluate the dorsal retroperitoneal space for the presence of ureterolithiasis; such a diagnosis relies on good radiographic technique and lack of interfering phenomena such as dirty film screens. Intravenous urography shows limited internal detail but is needed to demonstrate structure and point of termination of ureters.

Lower Urinary Tract

Ultrasonography of the bladder is invaluable, though artefacts such as side-lobe and spurious echo artefacts are common if inappropriate settings are used. The bladder wall thickness varies according to degree of bladder distension, normally being <1.5 mm or <1.7 mm in thickness, in dogs and cats respectively, when the bladder is moderately distended. Thickening may be seen with cystitis but absence of thickening does not rule this out. The ureteral papillae and jets may be appreciated. Mass lesions such as neoplasms and polyps may be seen (the former occurring more frequently in the trigone area and the latter more commonly at the bladder apex) but should not be confused with blood clots. Bladder calculi may be seen as hyperechoic rounded structures with distal acoustic shadowing. Type cannot be implied by ultrasonography, and radiography is superior for delineating numbers; they will usually move to the dependent part of the bladder. Ultrasonography is also useful to evaluate the prostate and the intraprostatic urethra but generally not the more distal urethra. Plain radiographs can be used to evaluate the bladder size and position and for the presence of radiodense uroliths. Note that the radiodensity of uroliths depends on their size and relative atomic number, and low atomic number stones such as urate may not be visible on plain radiographs. Radiographs must be taken in such a way that the intra- and extra-pelvic urethra is also included for evaluation; it is best evaluated by contrast urethrogram and this is a common omission. Sensitivity of radiography for identifying urolithiasis and mass lesions is increased progressively by performing single and double contrast studies which are described in detail elsewhere.

Other Tests

Urethrocystoscopy

Direct visualisation of the lower urinary tract is possible in dogs and female cats with a combination of rigid and flexible endoscopy. Male cats usually require antepubic cystoscopy. Fibreoptic viewing devices without ability to steer usually do not allow thorough evaluation. Urethrocystoscopy may also be used to perform biopsies and to retrieve small uroliths. In cases of suspected idiopathic renal haematuria, direct observation or cannulation of the ureters may identify the site of haemorrhage.

Advanced Imaging

Computed tomography (CT) and magnetic resonance imaging (MRI) have not been thoroughly evaluated in the investigation of haematuria in dogs and cats. The author has had limited experience using MRI in evaluation of occult upper urinary tract haematuria which has occasionally pinpointed renal lesions otherwise not found with more routine imaging techniques.

Biopsy

Biopsy of the urinary tract may be used to confirm the tissue of origin and nature of mass lesions. Renal biopsy may be performed with ultrasound guidance (tru-cut) or at surgery. Renal fine-needle aspirates are appropriate for diffuse cortical infiltrative disease, e.g., lymphoma. Tru-cut renal biopsies entail risk including severe haemorrhage and transient decline in renal function. It is important to discuss the potential hazards of biopsy with owners, to ensure that it is going to be of diagnostic value (unfortunately often limited), to assess coagulation status beforehand and to have a plan for post-biopsy monitoring. Ultrasound-guided fine-needle aspiration of bladder mass lesions is possible, but due to the risk of seeding of transitional cell carcinoma, either traumatic catheter suction biopsy or cystoscopic biopsy is preferable. Bladder wall biopsy is not recommended as a diagnostic test for feline idiopathic cystitis since reported histopathological changes in this condition are neither invariably present nor pathognomonic.

Bladder Tumour Antigen Testing

Tests for detection of bladder tumour antigen are commercially available. However, whilst these tests show high sensitivity and specificity when comparing dogs with lower urinary tract neoplasia to dogs without urinary tract disease, in the presence of haematuria due to other causes their specificity appears much poorer.

References

1.  Bartges JW. Discoloured urine. In: Ettinger, SJ; Feldman, EC. eds. Textbook of veterinary internal medicine (sixth edition). St. Louis: Elsevier Sunders, 2005; 112-114.

2.  Watson ADJ. Dysuria and haematuria. In: Elliott, J; Grauer, G. eds. BSAVA manual of canine and feline nephrology and urology (second edition). Gloucester: BSAVA, 2007; 1-7.