Isosthenuria is a term applied to a series of urine specimen from the same patient that exhibit a

Basic Information

Therapy and Diets That May Alter Results

Low urine specific gravity may be caused by fluid therapy, glucocorticoids, diuretics, anticonvulsants, and excessive thyroid hormone supplementation. Persistent use of low-protein diets can result in inability to maximally concentrate urine (usually blood urea nitrogen [BUN] concentrations are below normal in this situation). Increased specific gravity may be caused by radiographic contrast media if the preadministration urine specific gravity was less than 1.040 (if preadministration urine specific gravity was >1.040, urine specific gravity may decrease because of osmotic diuresis).

Note

It is important to obtain urine specific gravity before treatment, especially fluid or diuretic therapy.

10 What is urine specific gravity, and what portion of the nephron does it reflect?

Urine specific gravity is the ratio of the density of urine to the density of distilled water. Urine is denser than pure water because it contains excreted solutes. Therefore the urine specific gravity is always greater than 1.000. Specific gravity is affected by the number of solute particles in solution as well as their molecular weight. It is therefore a way to estimate a solution's osmolality, which is affected only by the number of solute particles in solution. The urine specific gravity primarily reflects the ability of the renal tubules to respond to the activity of antidiuretic hormone (ADH) to produce concentrated urine. To determine the clinical significance of a given urine specific gravity measurement, the value must be interpreted in light of the patient's hydration status, blood urea nitrogen (BUN), and serum creatinine.

Specific Gravity

a.

Urine specific gravity (USG) is the weight of the urine compared to that of an equal volume of water. It reflects both the total number of solutes and their weight (heavier molecules contribute more to USG than smaller ones).

Urine specific gravity provides the most meaningful information about renal function on the urinalysis.

1000 mg/dL glucose increases the USG approximately 0.004.

1000 mg/dL protein increases the USG approximately 0.003.

USG estimated by dipstrip pads is not accurate over a wide range of USG and should not be used.

USG is estimated by refractometry (refraction of light in solution is affected by the number and size of the particles in the solution).

The refractometer should be temperature compensated for accurate and consistent estimates of USG.

Dog and cat urine have different refractometric properties, and scales specifically developed for use in dogs or cats should be used for most accurate results.

Optical and digital refractometers designed for veterinary use have scales that allow determination of USG values up to 1.060.

Commonly available refractometers designed for use in humans only measure USG up to 1.035.

USG should not simply be reported as >1.035 in dogs and cats. When the initial USG reading exceeds the refractometer’s scale, mix equal volumes of urine and distilled water and determine the USG. Multiply the numbers to the right of the decimal point by a factor of 2 to determine the actual USG.

Use the USG as a guide to interpret the relative concentration of abnormal elements or chemical constituents in the sample.

4+ (1000 mg/dL) proteinuria in a urine sample of 1.010 USG represents more severe proteinuria than 4+ (1000 mg/dL) proteinuria in urine of 1.045 USG.

4 WBCs/high-power field (hpf) in urinary sediment from a urine sample of 1.060 USG may be less clinically relevant than 4 WBCs/hpf in urine sediment from a urine sample of 1.015 USG.

USG should be determined before treatment with fluids, diuretics, corticosteroids, or other medications.

Repeated production of submaximally concentrated urine in dogs and cats usually indicates abnormal renal function (see Chapter 2).

The first urine of the morning is most likely to have the highest solute concentration. USG will vary based on diet moisture content, amount of water consumed, excess dietary solutes requiring renal excretion, renal function, and hydration status (see Chapter 15, Approach to Polyuria and Polydipsia).

First urine of the morning should have USG >1.035 in cats consuming dry foods and >1.025 in cats consuming canned foods.

Average USG throughout the day should be >1.020 in dogs.

In dogs, often USG is >1.030 to 1.040 in samples of the first urine of the morning before consumption of food or water.

The USG of some dogs may vary widely throughout the day presumably as a result of eating, drinking, and activity.

Dehydrated dogs and cats should elaborate maximally concentrated urine (> 1.040 USG) if the hypothalamic-pituitary-adrenal-renal axis is normal.

Specific gravity

Urine specific gravity (SG) (or, more correctly, its osmolarity) is the only indicator of renal function in the urinalysis. Urinary specific gravity reflects the ability of the kidney to concentrate urine and is therefore a useful indicator of renal function.

The specific gravity of normal equine urine varies between 1.020 and 1.050.

Dehydration results in a more concentrated urine (SG over 1.035–1.055).

Pre-renal azotemia would be indicated by a high SG and elevated urea/creatinine concentrations.

The presence of dilute urine (SG of 1.005–1.020) in an azotemic (elevated creatinine and urea concentrations) or dehydrated horse is indicative of renal azotemia (tubular dysfunction).

Fluid therapy in a dehydrated pre-renal azotemia case would result in restoration of the normal concentrations of these metabolites. By contrast, a renal azotemia case would simply produce more urine of an equally dilute nature without normalization of the creatinine and urea concentrations. In acute renal failure, fluid therapy would not normally induce urination within 6 h of the initiation of fluid therapy.

On rare occasions, dilute urine may be found in a hydrated, non-azotemic horse as, for example, in diabetes insipidus (q.v.), psychogenic polydipsia (q.v.) or diseases that antagonize the action of antidiuretic hormone.

A 24 h water deprivation test (Box 12.3, q.v.) may be necessary to assess renal concentrating ability. However, it is imperative that the horse is carefully monitored during the test to avoid dangerous dehydration. Where dehydration is a real or potential hazard, urine-concentrating ability can be measured following the administration of exogenous antidiuretic hormone.

It should be noted that renal medullary washout is due to excessive drinking in the absence of pathology and follows the loss of osmotic gradient within the renal tubules. In this case it is possibly better to perform a partial water deprivation test. The partial water deprivation test is performed by restricting water intake to 40–45 mL/kg/day for several days; water should be offered in small volumes frequently through the day. This will usually restore the gradient, the urine SG will rise to >1.025 and the associated polydipsia will usually resolve. An increase in SG >1.025 suggests psychogenic polydipsia (q.v.) while failure to concentrate >1.025 suggests diabetes insipidus (q.v.).

Assessment of Urine Concentration

Urine specific gravity is a measure of the number of particles in urine and is a useful estimate of urine concentration. Although determination of specific gravity with a refractometer is quick and easy (reagent strips should not be used to measure specific gravity in horses),279 one must recognize that urine concentration is determined most accurately by measurement of urine osmolality, because the presence of larger molecules in urine, such as glucose or proteins, leads to overestimation of urine concentration by assessment of specific gravity. Clinically, overestimation is a problem in patients with diabetes or heavy proteinuria.155 Urine specific gravity is used to separate urine concentration into three categories: (1) urine that is more dilute than serum (hyposthenuria or specific gravity less than 1.008 and osmolality less than 260 mOsm/kg); (2) urine and serum of similar osmolality (isosthenuria or specific gravity of 1.008–1.014 and osmolality of 260–300 mOsm/kg); and (3) urine that is more concentrated than serum (specific gravity greater than 1.014 and osmolality greater than 300 mOsm/kg). Although urine of most normal horses is concentrated (3 to 4 times more concentrated than serum with specific gravity of 1.025–1.050 and an osmolality of 900–1200 mOsm/kg), occasionally a normal horse produces dilute or highly concentrated urine. For example, in response to water deprivation for 24 to 72 hours, horses with normal renal function often produce urine with a specific gravity greater than 1.045 and an osmolality greater than 1500 mOsm/kg.194,195,200 In contrast, foals typically have hyposthenuric urine consequent to their mostly milk diet.169 Although constant polyuria decreases the ability of the neonate to generate a large osmotic gradient in the medullary interstitium, dehydrated foals still can produce urine with a specific gravity greater than 1.030. With chronic renal insufficiency, the ability to produce concentrated (specific gravity greater than 1.025) or dilute (specific gravity less than 1.008) urine is lost. Thus horses with chronic kidney disease typically manifest isosthenuria. As discussed previously, urine specific gravity is helpful in differentiating prerenal from renal azotemia in horses that exhibit dehydration or shock with many disorders.

Low Urine Specific Gravity

The urine specific gravity in a dog with normal renal function and prerenal uremia secondary to dehydration and decreased cardiac output should be greater than 1.030, whereas urine specific gravity in a dog with primary renal failure is within or near the isosthenuric range (1.008 to 1.020). Most dogs with hypoadrenocorticism have an impaired ability to concentrate urine because chronic urinary sodium loss causes a reduction in the renal medullary sodium content, loss of the normal medullary concentration gradient, and impaired capacity for water resorption by the renal collecting tubules. Hyponatremia also interferes with stimulation of vasopressin release by reducing serum osmolality. As a result, 60% of dogs with hypoadrenocorticism have urine specific gravity consistent with that expected in a dog with primary renal failure (see Table 12-4). Thus it may be difficult to distinguish hypoadrenocorticism from primary renal failure without measurement of serum cortisol concentrations (Box 12-4); hypoadrenocorticism should always be considered in an ill dog with azotemia and isosthenuria.

Urinalysis

Urine specific gravity can be decreased in patients with hepatic insufficiency or PSS. This can be caused by an inability to fully concentrate urine, resulting in PU, or from primary PD.

Bilirubin is commonly measured semiquantitatively in canine and feline urine using urine dipsticks. Bilirubinuria (<2+ on a dipstick) can be a normal finding in dogs (especially males).82 Bilirubinuria in dogs without hemolytic or hepatobiliary disease can occur as a consequence of the loss of unconjugated bilirubin that is bound to albumin in proteinuric patients and renal filtration of small amounts of conjugated bilirubin that has leaked from the liver. Additionally, the renal tubular cells of male dogs have the enzymes needed to produce and conjugate bilirubin. As cats have a higher renal threshold for bilirubin than dogs, bilirubinuria should always be considered abnormal in cats. Bilirubinuria in cats and excessive bilirubinuria in dogs implies hemolytic or hepatobiliary disease. Because dogs have a relatively low renal threshold for bilirubin, bilirubinuria is often detected before bilirubinemia or jaundice.

Ammonium biurate crystals are detected in the urine sediment by light microscopy. Uric acid is a product of purine catabolism and is converted to allantoic acid by hepatic urate oxidase. In cases with severe hepatic insufficiency or PSS, the serum uric acid concentration may be higher than the renal threshold. This combined with hyperammonemia may lead to ammonium biurate precipitation in the urine. Urate urolithiasis seems to be more common in patients with PSS than those with other types of hepatic dysfunction. Between 40% and 70% of dogs with PSS were found to have urate crystalluria.83 However, it should be noted that urate crystalluria is not specific for hepatobiliary disease.

Assessment of Urine Tonicity

Urine specific gravity is a measure of the number of particles in urine and is a useful estimate of urine tonicity. Although determination of specific gravity with a refractometer is quick and easy (reagent strips should not be used to measure specific gravity in horses),29 it is important to recognize that urine tonicity is most accurately determined by measurement of urine osmolality (Uosm) because larger molecules in urine, such as glucose or proteins, can lead to overestimation of urine tonicity when assessed by specific gravity. Clinically, this is only a problem in patients with diabetes mellitus or heavy proteinuria. Unfortunately, most refractometers have an upper end of the specific gravity scale of 1.035, making it necessary to estimate the specific gravity of more concentrated samples by extrapolation. As an alternative, refractometers with a wider specific gravity scale (1–1.06) are available and may be worthwhile to purchase for equine hospitals. Finally, some refractometers use different scales for canine and feline urine, and the canine scale should be used for assessment of the specific gravity of equine urine.

Urine specific gravity or Uosm is used to separate urine tonicity into three categories: (1) urine that is more dilute than serum (hyposthenuria or specific gravity <1.008 and Uosm <260 mOsm/kg); (2) urine and serum of similar osmolality (isosthenuria or specific gravity of 1.008–1.014 and Uosm of 260–300 mOsm/kg); and (3) urine that is more concentrated than serum (specific gravity >1.014 and Uosm >300 mOsm/kg.30 Urine of most normal horses consuming dry forage is usually concentrated (two to four times the tonicity of serum) with a specific gravity of 1.025 to 1.04 and a Uosm of 600 to 1200 mOsm/kg, whereas horses at pasture may have more dilute urine because of the high water content of grass. When deprived of water for 24 to 72 hours, horses with normal renal function produce urine with a specific gravity greater than 1.045 and an Uosm greater than 1500 mOsm/kg.31 In contrast, neonatal foals typically have hyposthenuric urine because their diet consists largely of milk.32 Because the volume of fluid intake as milk by foals up to 60 days of age is nearly fivefold the fluid intake of an adult horse (on an mL/kg basis), healthy foals are polyuric and their urine appears clear with little yellow color. Another consequence of this high fluid intake and associated diuresis is that the BUN and Cr values in foals may be near or below the lower limit of the adult reference ranges. Further, although this fluid intake decreases a foal's ability to generate an osmotic gradient in the medullary interstitium, foals can still produce urine with a specific gravity greater than 1.03 when dehydrated.

Urine tonicity can be used to differentiate prerenal failure from intrinsic renal failure. With prerenal failure, maintenance of urinary concentrating ability is demonstrated by a specific gravity greater than 1.02 and a Uosm greater than 500 mOsm/kg, and values are often much higher. In contrast, with intrinsic renal failure urinary concentrating ability is lost: specific gravity and Uosm are typically less than 1.02 and less than 500 mOsm/kg, respectively, in the face of dehydration.33 Assessment of urine tonicity can be problematic, however, because it is only valid when performed on urine collected before initiating fluid therapy or administering medications (e.g., α2-receptor agonists or furosemide) that can affect urine flow and tonicity.34

Specific Gravity

Assessment of urine specific gravity is an essential test when renal pathology is suspected or if serum chemistry confirms azotemia. Isosthenuria (USpG of 1.006-1.014) in dehydrated or azotemic cattle is indicative of renal dysfunction because normal renal function should concentrate urine in a dehydrated patient. Unilateral renal ischemia or disease usually does not result in isosthenuric specific gravity of urine. With acute renal failure, the specific gravity is not always in the isosthenuric range, but it is no higher than 1.022, even in the face of dehydration. Healthy lactating dairy cows and milk-fed calves normally have low urine specific gravity (1.004–1.015), and when the specific gravity is greater than 1.025, dehydration should be considered.