Diagnostic Approach to PU/PD: Urine Specific Gravity

Urinalysis is a major key in determining the presence of a water balance problem and the disorder causing the polyuria and polydipsia. The most important features of urinalysis are: the SG or osmolality; the presence or absence of glucose, protein or bacteria; and the cellularity of the sample.

A urine SG less than 1.030 in dogs and 1.035 in cats suggests a concentrating defect and supports the complaint of polyuria. Persistent glycosuria is diagnostic for primary renal glycosuria or, more commonly, diabetes mellitus. Significant proteinuria in the presence of an inactive urinary sediment and dilute urine can be associated with hyperadrenocorticism, pyelonephritis, pyometra, glomerulonephritis or other glomerulopathy.

An active urine sediment (pyuria, hematuria or bacteriuria) in a sample obtained by catheterization or cystocentesis supports urinary tract infection and possible pyelonephritis. Because urine sediment examination may be misleading in an extremely dilute urine sample, a urine culture should always be done to rule out pyelonephritis, regardless of sediment examination findings.

If the results of the above tests are unhelpful the direction of further diagnostic work-up can often be based on the urine SG (see Table below). For example, dogs and cats with a SG greater than 1.030--1.035 without glycosuria, are probably not polyuric and need no further work-up, at least for polyuria and polydipsia.

---

Differential diagnosis based on urine specific gravity (SG) determination in animals with normal results of initial tests (CBC, serum biochemical profile and urinalysis).

Urine SG of 1.001--1.007

• Atypical hyperadrenocorticism (most common; always rule out first!)
  
• Atypical leptospirosis
  
• Psychogenic polydipsia
  
• Diabetes insipidus (complete)

Urine SG of 1.008--1.029

• Atypical hyperadrenocorticism (most common!)
  
• Atypical leptospirosis
  
• Early renal disease
  
• Typical and occult pyelonephritis
  
• Hyperthyroidism (cats)
  
• Psychogenic polydipsia
  
• Diabetes insipidus (partial)

Urine SG greater than 1.030 (without glycosuria)

• probably No further work-up for polyuria and polydipsia needed.

---

Urine SG less than 1.008 A urine SG consistently less than 1.008 in a middle-aged to older dog is usually associated with diabetes insipidus, psychogenic polydipsia, atypical hyperadrenocorticism or atypical leptospirosis.

In these dogs with atypical hyperadrenocorticism, polyuria and polydipsia are major clinical signs but other characteristic clinical signs are mild or absent. In addition, these dogs with atypical disease may lack the serum biochemistry abnormalities commonly associated with hyperadrenocorticism (i.e. elevated serum alkaline phosphatase activity and hypercholesterolaemia). Results of adrenal function tests in these dogs are usually consistent with mild hyperadrenocorticism.

More recently an atypical form of leptospirosis has been recognized. These dogs present with an acute onset polyuria and polydipsia, hyposthenuria or isosthenuria, but no other laboratory abnormalities. Diagnosis of leptospira infection can be confirmed by positive leptospirosis serology or use of molecular detection of leptospiral DNA by polymerase chain reaction (PCR) testing performed on urine samples.

In general, when considering polyuric dogs with a urine SG less than 1.008, hyperadrenocorticism and atypical leptospirosis should be ruled out first before testing for central diabetes insipidus and primary polydipsia. There are several reasons for making this recommendation: the latter two disorders of water metabolism are much less common than hyperadrenocorticism (see Table below); the diagnostic tests of choice to differentiate these disorders – the water deprivation test or a therapeutic trial with the AVP-analogue desmopressin – are time-consuming and expensive. Also, dogs with hyperadrenocorticism may respond to these tests in a manner similar to dogs with central diabetes insipidus, resulting in a misdiagnosis. Moreover, water deprivation testing a dog with leptospirosis would be a major contraindication because of the possibility of causing significant patient morbidity.

---

Differential rule outs for polyuria and polydipsia in dogs and cats, listed from most to least common. Dogs

• Hyperadrenocorticism
  
• Diabetes mellitus
  
• Chronic renal failure
  
• Pyelonephritis
  
• Pyometra
  
• Hypercalcaemia
  
• Atypical leptospirosis
  
• Psychogenic polydipsia
  
• Diabetes insipidus
  
• Liver disease
  
• Hypoadrenocorticism
  
• Acromegaly
  

Cats

• Chronic renal failure
  
• Diabetes mellitus
  
• Hyperthyroidism
  
• Hypercalcaemia
  
• Pyelonephritis
  
• Hypokalaemia
  
• Acromegaly
  
• Postobstructive diuresis
  
• Hyperadrenocorticism
  
• Hypoadrenocorticism
  
• Diabetes insipidus

---

In cats, a urine SG consistently less than 1.008 is associated with either diabetes insipidus or hyperthyroidism. Obviously, hyperthyroidism should be ruled out first before initiating testing procedures for diabetes insipidus. It is also important to realize that the finding of a urine SG less than 1.008 in a cat or dog excludes mild (occult) renal disease, so precautions associated with the water deprivation test are not necessary.

Urine SG between 1.008 and 1.029

A urine SG of 1.008--1.012 or greater (but less than 1.030) can be associated with hyperadrenocorticism (dogs), hyperthyroidism (cats), or stage 1 renal insufficiency (including atypical leptospirosis) or pyelonephritis, as well as psychogenic polydipsia and partial forms of diabetes insipidus. 

Again, when considering animals with a urine SG greater than 1.008 hyperadrenocorticism and hyperthyroidism should first be ruled out. With this group of disorders, pyelonephritis and early renal insufficiency should next be ruled out before evaluating the animal for psychogenic polydipsia and diabetes insipidus with a water deprivation test. Performing a water deprivation test as a diagnostic tool in the face of unsuspected renal insufficiency or pyelonephritis could induce overt renal failure or urosepsis. To avoid this complication, a sensible approach is to do the following:

1. Perform a urine culture to help exclude pyelonephritis and associated urinary tract infection.
   
2. Consider leptospirosis serology and urine PCR testing.
   
3. Evaluate renal size and architecture by abdominal radiography or, preferably, renal ultrasonography. The ultrasonographic appearance of renal parenchymal disease (chronic renal failure) includes increased cortical echogenicity and loss of a distinct corticomedullary junction. The kidneys may appear smaller than normal and have an ill-defined or irregular border. Similar sonographic findings, in addition to a dilated renal pelvis, are characteristic of pyelonephritis.

If urine culture results are negative, leptopirosis serology and urine PCR testing are negative, and radiographic or ultrasonographic findings are equivocal, a creatinine or iohexol clearance test or renal biopsy may be indicated. In rare cases, the urine culture may be negative even if pyelonephritis is present. If clinical or ultrasonographic findings suggest occult pyelonephritis, a therapeutic trial with an appropriate antibiotic (e.g. enrofloxacin) should be instituted.

In the next post, I will talk about when water deprivation testing is needed in the workup of dogs and cats with PU/PD.

Diagnostic Approach to Polyuria and Polydipsia

Differentiating between the causes of polyuria and polydipsia (PU/PD) is relatively easy when the different disorders are manifested in their classic forms. For example, polyuria that develops after a known head trauma, continues after water restriction and decreases after AVP administration does not require additional tests to justify the diagnosis of central diabetes insipidus. A diagnosis of congenital nephrogenic diabetes insipidus is equally clear if polyuria occurs in a young animal with similarly affected litter mates that have normal screening laboratory tests (including renal function), negative urine cultures and whose polyuria fails to respond to fluid restriction or administration of AVP analogues (e.g. desmopressin).

Often, however, the clinical setting is of minimal help in making a diagnosis and it is then necessary to perform more detailed diagnostic tests. The initial information gathered should allow the inclusion or exclusion of the many common medical disorders associated with polyuria and polydipsia before a diagnostic work-up for the less common disorders of central diabetes insipidus, primary nephrogenic diabetes insipidus or psychogenic polydipsia is embarked upon.

Measurement of water consumption
The first step in any suspected case of polyuria and polydipsia is to establish that the problem actually exists, preferably by a combination of history, random urine SG determinations and, if necessary, home measurement of water consumption over several days.

If the daily water intake is found to be normal or if a random urine SG determination is >1.035, additional history should be obtained to rule out other urinary tract disorders (such as urinary incontinence or dysuria) that commonly are confused with polyuria. If, however, random urine SG are consistently <1.030 in dogs and <1.035 in cats, and daily water intake is >100 ml/kg for dogs and 45 ml/kg for cats, polyuria and polydipsia are indeed present and a diagnostic work-up to determine the cause is warranted.

Minimum clinicopathological data
Once a problem of water balance is confirmed, a practical diagnostic approach is to first rule out the more common causes of polyuria and polydipsia in dogs and cats. Recommended initial diagnostic tests include:

• Complete blood cell count (CBC)
  
• Serum biochemical profile with electrolytes
  
• Serum total thyroxine (T4) determination in middle-aged to older cats

A careful evaluation of this initial database, together with the history and results of physical examination, usually provides the diagnosis immediately (e.g. overt renal failure, hyperthyroidism or diabetes mellitus) or offers clues to as to the underlying cause of the polyuria and polydipsia (see Table below). For example, dogs with hyperadrenocorticism commonly have a stress leucogram (i.e. neutrophilia, lymphopenia and eosinopenia). Over 90% of dogs with hyperadrenocorticism also have high alkaline phosphatase (ALP) activity, whereas over half have hypercholesterolaemia.

In contrast, physical examination findings and routine blood work are generally unremarkable in animals with less common causes of polyuria and polydipsia such as central diabetes insipidus, primary nephrogenic diabetes insipidus and psychogenic polydipsia. When abnormalities are present, they are usually secondary to dehydration caused by water restriction by the owner. Such abnormalities may include a slightly increased packed cell volume (PCV) or hypernatraemia.

---

Initial work-up for polyuria and polydipsia in dogs and cats.

Signalment and history

• Age, breed and sex
  
• Reproductive history (intact female?)
  
• Changes in diet or environment?
  
• Overall general health (weight loss or gain, lethargy, vomiting or diarrhoea?)
  
• Appetite normal, increased or decreased?
  
• Drug administration (glucocorticoids, anticonvulsants, diuretics?)

Physical examination

• Kidneys small or misshapen? (chronic renal disease)
  
• Kidneys large? (pyelonephritis, lymphosarcoma)
  
• Hepatomegaly? (hyperadrenocorticism, diabetes mellitus)
  
• Peripheral lymphadenopathy? (lymphosarcoma with hypercalcaemia)
  
• Perianal mass? (anal sac adenocarcinoma with hypercalcaemia)
  
• Vaginal discharge? (pyometra)
  
• Alopecia? Pot belly? (hyperadrenocorticism)
  
• Thyroid mass? (hyperthyroidism)

Complete blood count (CBC), serum biochemical profile and electrolytes, serum thyroxine

• High urea or creatinine? (renal failure)
  
• Hyperglycaemia? (diabetes mellitus)
  
• High alkaline phosphatase activity (hyperadrenocorticism)
  
• Hypercholesterolaemia? (hyperadrenocorticism)
  
• Hypercalcaemia?
  
• Hypokalaemia?
  
• High thyroxine? (hyperthyroidism)

Complete urinalysis and urine culture

• Low urine specific gravity (confirms and defines polyuria)
  
• Proteinuria? (hyperadrenocorticism, pyometra, pyelonephritis, glomerulonephritis)
  
• Glucosuria +/- ketonuria? (Diabetes mellitus)
  
• Active urine sediment? (infection, pyelonephritis)
  
• Positive bacterial culture? (infection, pyelonephritis)

Abdominal radiography or ultrasonography

• Small kidneys with ill-defined renal or irregular border (renal failure)
  
• Increased cortical echogenicity, indistinct corticomedullary junction (renal failure)
  
• Dilated renal pelvis (pyelonephritis)

---

Our next blog post we will continue discussing the diagnostic approach to PU/PD, concentrating on the urine's specific gravity.

What's the Differential Diagnosis of Polydipsia and Polyuria in Dogs and Cats?

There are many potential causes of polyuria and polydipsia.  Primary disorders of water balance (i.e. central diabetes insipidus, primary nephrogenic diabetes insipidus and primary polydipsia) although uncommon, should always be considered in the differential diagnosis of polyuria and polydipsia. In general, animals with these disorders have only one laboratory abnormality; a low urine specific gravity (SG) or osmolality.

In most instances the more common causes of polyuria and polydipsia (e.g. hyperadrenocorticism, chronic renal failure, pyelonephritis and pyometra) have other specific and obvious abnormalities on screening laboratory tests (complete blood cell count, serum biochemical profile and urinalysis). In some cases, however, a low urine SG is the only abnormality found in animals with these latter disorders.

The work-up for polyuria and polydipsia can be tedious, time-consuming, expensive, confusing and not without significant patient morbidity, especially in those dogs and cats with normal or near-normal screening test results. This chapter focuses on the diagnostic approach, especially the problems associated with testing, and the treatment of dogs and cats with disorders of water balance.

Differential diagnosis
The causes of polyuria and polydipsia can be divided into those that cause primary polydipsia (with secondary polyuria) and those that cause primary polyuria (with compensatory polydipsia). These are listed in the table below.

The major cause of primary polydipsia in dogs is psychogenic polydipsia. In contrast, the causes of primary polyuria are much more numerous and can be subdivided into the categories of: central diabetes insipidus; primary nephrogenic diabetes insipidus; secondary nephrogenic diabetes insipidus; and osmotic diuresis.

---

DIFFERENTIAL DIAGNOSIS OF POLYDIPSIA AND POLYURIA

1. Primary polydipsia

• Psychogenic polydipsia (compulsive water drinking)
  
• Dipsogenic diabetes insipidus (thirst centre abnormality)
  
• Metabolic disorders (e.g. hyperthyroidism, hepatic failure)

2. Primary polyuria

Central diabetes insipidus (neurogenic, cranial, ADH-responsive)

• Idiopathic
  
• Trauma-induced
  
• Neoplastic
  
• Post-hypophysectomy

Primary nephrogenic diabetes insipidus (congenital or familial)

Secondary nephrogenic diabetes insipidus (acquired)

• Acromegaly
  
• Chronic renal disease
  
• Drug administration
  
• Liver disease
  
• Hyperadrenocorticism
  
• Hypercalcaemia
  
• Hyperthyroidism
  
• Hypoadrenocorticism
  
• Hypokalaemia
  
• Leptospirosis
  
• Postobstructive diuresis
  
• Pyelonephritis
  
• Pyometra

Osmotic diuresis (increased renal tubular solute load)

• Diabetes mellitus
  
• Primary renal glycosuria (e.g. Fanconi’s syndrome)
  
• Postobstructive diuresis
  
• Renal failure
  
• Leptospirosis

---

In our next blog post, I will talk about my approach to working up the dog or cat with polyuria or polydipsia.