Proceeding of the ACVP Annual Meeting

http://www.ivis.org Proceeding of the ACVP Annual Meeting Oct.17-21, 2015 Minneapolis, MN, USA Next Meeting: Dec. 3-7, 2016 - New Orleans, LA, USA Reprinted in the IVIS website with the permission of the ACVP

URINALYSIS GETTING SPECIFIC ABOUT SPECIFIC GRAVITY AND OTHER IMPORTANT FEATURES Jody Lulich, DVM PhD, Minnesota Urolith Center, University of Minnesota, St Paul, MN Determining urine specific gravity is essential to localize azotemia, diagnose kidney failure (CKD), verify and localize the cause of polyuria, accurately interpret every urinalysis result, accurately interpret many serum biochemical values, ensure effective management of the acutely ill patient, and verify compliance of administration of several prescription foods and medications. Although urine specific gravity is a simple, easy, rapid, and inexpensive test to perform it is often overlooked or not requested until a time when its interpretation is confounded by treatment (i.e. after fluid therapy or medications that alter urine concentrating mechanisms) even though it is most useful when measured prior to therapy. The kidneys play a fundamental role in tightly regulating plasma volume and composition to maintain osmolality despite fluctuations in fluid consumption, diet and disease. Regulation of water and solutes is the result of careful adjustments in glomerular filtration, tubular reabsorption, and tubular secretion. Measurement of urine osmolarity directly by osmometry or indirectly by urine specific gravity is the primary method used to evaluate the kidney s response (i.e. concentration-removing water in excess of solute, or dilution-removing solute in excess of water) to the water needs of the body. Thus, evaluation of urine osmolarity or specific gravity is an index of tubular reabsorption of water in relation to solutes. Increased thirst and urine production are common owner concerns. Knowledge of specific gravity is essential to verify polyuria and to differentiate its underlying causes (table 1). Another essential indication for routine evaluation of urine specific gravity involves interpretation of tests that are part of the complete urinalysis. Specific gravity is also used as an aid to monitor the patient s fluid balance, especially during need for therapy with parenteral fluids. Most importantly urine specific gravity is used to localize azotemia and differentiate primary renal failure (table 2) from other polyuric disorders. DOES THIS DOG HAVE KIDNEY FAILURE? Normal Weight (kg) 13 Creatinine mg/dl 2.1 0.6 to 1.5 BUN (mg/dl) 44.0 14 to 33 Phosphorus (mg/dl) 5.2 4 to 8 Potassium 4.5 4 to 6 Hematocrit (%) 56 36 to 56 U Specific Gravity 1.003 Your Answer

Glossary of Common Terms Normal Urine specific gravity The specific gravity of normal animals is variable, being dependent on the fluid and electrolyte balance of the body, the protein, mineral and water composition of the diet, and other variables related to the species and individual. Urine specific gravity typically fluctuates widely from day to day and within the same day. A typical normal range for the dog is 1.001 to 1.060 in dogs and 1.001 to 1.080 in cats. Depending on the requirements of the body for water and/or other solutes, any specific gravity value within this range may be normal. Therefore, the concept of an average normal specific gravity is misleading because it implies that values below or above the average may be abnormal. Concentrated Urine Urine is concentrated if it is significantly above the specific gravity of glomerular filtrate (greater than 1.008 to 1.012). The ability of patients to excrete concentrated urine is dependent on 1) a functional nervous system for production and release of antidiuretic hormone, 2) a sufficient number of nephrons to generate and maintain a high solute concentration in the renal medulla, and 3) a sufficient population of functioning tubules to respond to antidiuretic hormone. Data from partially nephrectomized dogs suggest that only about 1/3 of the nephrons of both kidneys is required to concentration urine to 1.030 or greater. Dilute urine Urine is dilute if it is significantly below the specific gravity of glomerular filtrate (less than 1.008 to 1.012). Metabolic work is required to dilute glomerular filtrate by removing solutes in excess of water. Therefore, a urine specific gravity below 1.008 indicates that a sufficient number of functioning nephrons (commonly estimated to be at least 1/3 of the total population, but urine dilution occurs even if functioning kidney mass is less than 1/3) are present to dilute urine, and therefore prevent the clinical signs associated with primary renal failure. Dilution is an appropriate and expected clinical response to over-hydration. However, formation of dilute urine when the patient is in negative water balance is abnormal and is usually an indication of the inability of antidiuretic hormone to stimulate receptors on distal renal tubules and collecting ducts (necessary to assemble water channels; examples include hypokalemia, hypercalcemia, urinary obstruction, nephrogenic diabetes insipidus), inability of the kidneys to generate a hyperosmotic medullary interstitium (recall that water only moves passively and needs a osmotic gradient; examples include kidney failure, hypoadrenocorticism, loop diuretics, decreased urea production), osmotic diuresis (diabetes mellitus and glucosuria, kidney failure and postobstructive diuresis), and lack of antidiuretic hormone (for example central diabetes insipidus). Hypersthenuria

Urine specific gravity much greater than that of glomerular filtrate (i.e. greater than 1.008 to 1.012). These values are often >1.030 in dogs and >1.035 in cats. Hyposthenuria Urine specific gravity that is less than glomerular filtrate (i.e. less than 1.008 to 1.012) Isosthenuria Urine specific gravity greater that is similar to glomerular filtrate (i.e. 1.008 to 1.012) Inappropriate urine concentration Urine specific gravity that is inappropriately low (i.e. below 1.030 in dogs and below 1.035 in cats) in patients that are dehydrated or azotemic that are not receiving drugs or other therapy, which may prevent or interfere with urine concentration mechanisms. A better Method of Classifying Urine Concentration As clinicians, we often refer to values being within or outside of the normal range. However, this is not possible with the urine specific gravity (and many of the other values of the urinalysis). Why? Because kidneys function to maintain plasma osmolality within a very narrow range. They do so by concentrating or diluting glomerular filtrate. Consequently, a low urine specific gravity (e.g. 1.008) may not be abnormal, but reflect the kidneys appropriate response to increased fluid intake. How urine specific gravity is interpreted not only depends on its value but also on the hydration status of the body and the conditions or diseases that alter or interfere with normal kidney function. We recommend that as an alternative to a normal reference range commonly used for serum biochemical values, a more clinically useful designation for urine specific gravity would be 1) maximally concentrated (near 1.060 for dogs and near 1.080 for cats; in order for the kidney to concentrate to this level kidneys have to be in high functioning order), 2) adequately concentrated ( 1.030 for dog and 1.035 to 1.040 for cats; we use the term adequately to indicate that it is adequately concentrated to prevent the signs of primary kidney failure (e.g. vomiting, anorexia)), or 3) inappropriate concentrated (between 1.007 and 1.030 for dogs and between 1.007 and 1.035 to 1.040 for cats); urine specific gravity is only inappropriate in animals that are dehydrated or azotemic (because in these conditions the kidneys would normally conserve water by forming a more concentrated urine). In animals that are adequately hydrated and not azotemic, urine specific gravity can encompass the entire physiological range (approximately 1.001 to 1.060 in dogs and 1.001 to 1.080 in cats) depending on the body s need to conserve or remove water.

Table 1. Interpreting Urine Specific Gravity Urine specific gravity Hydration Status Azotemia Classification of urine concentration Interpretation Associated clinical conditions 1.050-1.060 (D) 1 Normal No Maximal Very Healthy kidneys Health 1.060-1.080 (C) 1 Dehydrated No Maximal Healthy kidneys Dehydration from any cause Dehydrated Yes Maximal Prerenal Azotemia Vomiting-common Water restriction-common >1.030-1.040 (D) >1.035-1.050 (C) <1.030 (D) <1.035-1.040 (C) Normal No Adequate 2 Healthy Health Dehydrated No Adequate Renal function is sufficient to maintain Health Nonazotemic kidney disease homeostasis Dehydrated Yes Adequate Prerenal azotemia Health Nonazotemic kidney disease Normal No Normal Renal function is sufficient to maintain homeostasis Dehydrated No Inappropriate Impaired renal function such that water homeostasis is disrupted Health Excessive water consumption Nonazotemic kidney disease Kidney disease Diseases inhibiting generation of a hyperosmotic renal medulla (e.g. hypercortisolemia; table 2). Diseases reducing renal tubular sensitivity to ADH (e.g. UTI, Table 2) Conditions promoting osmotic diuresis (e.g. glucosuria, fluid administration; table 2) Dehydrated Yes Inappropriate Kidney failure (CKD) Kidney failure (CKD) 1.008-1.012 Normal No Normal Healthy Health Possible early kidney disease Hypervolemic Yes Fixed Advanced kidney failure (disease) Later or end stage kidney failure (disease) Dehydrated No Inappropriate Impaired renal function such that water homeostasis is disrupted Kidney disease Diseases inhibiting generation of a hyperosmotic renal medulla (e.g. Structural kidney disease, hypercortisolemia; table 2). Diseases reducing renal tubular sensitivity to ADH (e.g. kidney failure, UTI, Table 2) Conditions promoting osmotic diuresis (e.g. glucosuria, fluid administration; table 2) Dehydrated yes Inappropriate Kidney failure Kidney failure <1.007 Normal or hypervolemic No Normal Healthy Health Polydipsia Excessive fluid administration Dehydration No Inappropriate Lack of ADH or insensitivity to ADH Central diabetes insipidus Nephrogenic diabetes insipidus Dehydrated Yes Inappropriate Lack of ADH or insensitivity to ADH Prerenal azotemia combined with central diabetes insipidus or nephrogenic diabetes insipidus 1. Administration of iodinated contrast agents may falsely elevate USG 2. Adequate implies that USG is adequately (e.g. sufficiently) concentrated such that the primary renal failure is unlikely D= dog, C= cat, USG= urine specific gravity, ADH=Antidiuretic hormone, UTI=urinary tract infection

Clinical Assessment of Polyuria and Polydipsia Polyuria and polydipsia (PU/PD) are frequent presenting concerns in small animal practice. Polyuria is defined as a daily urine output of greater than 50 ml/kg per day, while polydipsia is defined as a fluid intake of more than 100 ml/kg/day. Healthy dogs generally consume between 50-60 ml/kg/day depending on the moisture content of their diets, the ambient temperature and humidity and their level of activity. Normal urine production is approximately 20-40 ml/kg/day or, 1-2 ml/kg/hour. The balance between water loss and water intake results from interactions between the hypothalamus, the pituitary gland and the kidney, and is maintained by thirst and renal excretion of water and electrolytes. The first step in evaluating a patient for polyuria/polydipsia is confirmation (a well defined problem is half solved; in polyuric states it is the expectation that urine concentration would be low, typically below 1.020). Polyuria and polydipsia may be a component of other urinary tract diseases as well. There are several approaches to evaluating patients with polyuria/polydipsia. In young dogs that are considered healthy on the basis of the initial evaluation, consider having the owner collect 3 to 5 early morning urine samples from their dog prior to water and food consumption. If any sample has a urine specific gravity greater than 1.025, polyuria/polydiposia is intermittent or misinterpreted. If confirmed, strive to determine if the cause of is a primarily polyuric state (serum biochemical evidence of hemoconcentration) or a primary polydipsic state (serum biochemical evidence of overhydration). Diseases associated with primary polyuria include those causing an osmotic diuresis, antidiuretic deficiency, or a lack of response of the kidneys to ADH (table 2). Results of the serum biochemistry profile and urinalysis are also an easy approach to rule-in or rule-out common diseases. In dogs, renal failure, diabetes mellitus, and hyperadrenocorticism are common causes for primary polyuria; while in cats, renal failure, diabetes mellitus, and hyperthyroidism are common causes. Table 2. MECHANISMS OF POLYURIA POLYURIA driven Lack of Antidiuretic Hormone (rare) Central diabetes insipidus Idiopathic Trauma Neoplasia Renal insensitivity to Antidiuretic Hormone Primary Nephrogenic Diabetes Insipidus Inherited Congenital Secondary Nephrogenic Diabetes Insipidus (common) Tubular Insensitivity to Antidiuretic Hormone Hypercalcemia Hypokalemia

Endotoxins (Pyometra, pyelonephritis, leptospirosis) Hyperadrenocorticism Excessive Growth Hormone Postobstructive diuresis Inability to Generate a Concentrated Medulla Renal failure Decreased urea production Liver failure Low protein diets Loop diuretic Hypertension Hypoadrenocorticism Hyperthyroidism Osmotic diuresis (common) Excessive Fluid Administration Diabetes mellitus Primary Glucosuria Fanconi Syndrome Post-obstructive diuresis Mannitol Renal failure POLYDIPSIA-driven Psychogenic Idiopathic Brain disease Hypothalamic mass Hepatic encephalopathy Others Physiologic Hypovolemia Fever Stress Pain KEYPOINT: If clinical signs warrant evaluation of renal function, urine specific gravity should be evaluated at the same time before instituting.

Table 2. Localizing Azotemia Localization of Azotemia Blood concentrations of urea nitrogen & Creatinine Urine Specific gravity Prerenal Increased Dog 1.030 Cat 1.040 Renal Increased Dog 1.030 Cat 1.035-1.040 Clinical Signs oliguria Variable Anorexia Vomiting Weight-loss Renal pain Renal hematuria Hx of nephrotoxins Post renal Increased Variable Oliguria Anuria Dysuria Painful Abdomen Comments Rapid correction following appropriate fluid therapy Rupture of the excretory system is usually associated with fluid in the abdomen. Creatinine concentration of abdominal fluid is higher than blood concentration of creatinine. Conclusion: Urine specific gravity is a simple and rapid test that is often underutilized. Remember that no laboratory test is fool proof. Understanding the mechanisms of urine concentration is essential to accurately interpret results in light of normal physiology and concomitant disease. Therefore, urine specific gravity needs to be interpreted in relation to patient history (e.g. medications, fluid administration, and diet), physical exam findings (e.g. hydration status), and other laboratory data (e.g. azotemia). Refractometers to Measure Urine Specific Gravity of Feline Urine 1. American Optical model #10438. 2. HSK-VET made by Heska (1-800-go-heska) This instrument also has the separate dog/large animal and cat scales. They currently sell this for $250.00 USD.

3. Misco Digital Refractometer. VetMed02 or VetMed01 order #PA202X This instrument also has separate species scales. We have not had experience using this digital model. References Osborne CA, Stevens JB. Urinalysis: a clinical guide to compassionate patient care. Bayer Corporation, Shawnee Mission Kansas USA, 1999. Watson ADJ, Urine specific gravity in practice. Austrailian Veterinary Journal. 1998; 76. 392-398. George JW. The usefulness and limitations of hand-held refractometers in veterinary medicine: an historical and technical review. Veterinary Clinical Pathology. 2001;30:201-210.