LABORATORY DIAGNOSIS: URINE STUDIES

For a routine screening urinalysis, a fresh (less than 1-h old), clean-catch urine is acceptable. If it cannot be interpreted immediately, it should be refrigerated (urine standing at room temperature for long periods causes lysis of casts and red cells and becomes alkalinized.)

URINALYSIS, NORMAL VALUES

Appearance: "Yellow, clear," or "straw-colored, clear"

Specific Gravity:

• Neonate: 1.012

• Infant: 1.002-1.006

• Child and Adult: 1.001-1.035 (with normal fluid intake 1.016-1.022)

pH:

• Newborn/Neonate: 5-7

• Child and Adult: 4.6-8.0

Negative for: Bilirubin, blood, acetone, glucose, protein, nitrite, leukocyte esterase, reducing substances

Trace: Urobilinogen

RBC:

• Male 0-3/hpf

• Female 0-5/hpf

WBC: 0-4/hpf

Epithelial Cells: Occasional

Hyaline Casts: Occasional

Bacteria: None

Crystals: Some limited crystals based on urine pH (see below)

 

Appearance

• Colorless: Diabetes insipidus, diuretics, excess fluid intake

• Dark: Acute intermittent porphyria, malignant melanoma

• Cloudy: Urinary infection (UTI) (pyuria), amorphous phosphate salts (normal in alkaline urine), blood, mucus, bilirubin

• Pink/Red:

• Heme-positive - Blood, hemoglobin, sepsis, dialysis, myoglobin

• Heme-negative - Food coloring, beets, sulfa drugs, nitrofurantoin, salicylates

• Orange/Yellow: Dehydration, phenazopyridine (Pyridium), rifampin, bile pigments

• Brown/Black: Myoglobin, bile pigments, melanin, cascara, iron, nitrofurantoin, alkaptonuria

• Green: Urinary bile pigments, indigo carmine, methylene blue

• Foamy: Proteinuria, bile salts

pH

• Acidic: High-protein (meat) diet, ammonium chloride, mandelic acid and other medications, acidosis, (due to ketoacidosis [starvation, diabetic], chronic obstructive pulmonary disease (COPD)

• Basic: UTI, renal tubular acidosis, diet (high-vegetable, milk, immediately after meals), sodium bicarbonate therapy, vomiting, metabolic alkalosis

Specific Gravity - Usually corresponds with osmolarity except with osmotic diuresis.

Normal: Value >1.023 indicates normal renal concentrating ability. Random value 1.003-1.030

Increased: Volume depletion; Congestive heart failure (CHF); adrenal insufficiency; diabetes mellitus; Syndrome of inappropriate antidiuretic hormone (SIADH); increased proteins (nephrosis); if markedly increased (1.040-1.050), suspect artifact or excretion of radiographic contrast media

Decreased: Diabetes insipidus, pyelonephritis, glomerulonephritis, water load with normal renal function

Bilirubin

Positive: Obstructive jaundice (intrahepatic and extrahepatic), hepatitis. (Note: False-positives occur with stool contamination.)

Blood

Note: If the dipstick is positive for blood, but no red cells are seen, free hemoglobin from trauma may be present; a transfusion reaction may have occurred, from lysis of RBCs (RBCs will lyse if the pH is <5 or >8); or myoglobin may be present because of a crush injury, burn, or tissue ischemia.

Positive: Stones, trauma, tumors (benign and malignant, anywhere in the urinary tract), urethral strictures, coagulopathy, infection, menses (contamination), polycystic kidneys, interstitial nephritis, hemolytic anemia, transfusion reaction, instrumentation (Foley catheter, etc)

Glucose

Positive: Diabetes mellitus, pancreatitis, pancreatic carcinoma, pheochromocytoma, Cushing's disease, shock, burns, pain, steroids, hyperthyroidism, renal tubular disease, iatrogenic causes. (Note: Glucose oxidase technique in many kits is specific for glucose and will not react with lactose, fructose, or galactose.)

Ketones - Detects primarily acetone and acetoacetic acid and not -hydroxybutyric acid.

Positive: Starvation, high-fat diet, diabetic ketoacidosis (DKA), vomiting, diarrhea, hyperthyroidism, pregnancy, febrile states (especially in children)

Nitrite - Many bacteria will convert nitrates to nitrite. (See also the section on Leukocyte Esterase.)

Positive: Infection (A negative test does not rule out infection because some organisms, such as Streptococcus faecalis and other gram-positive cocci, do not produce nitrite, and the urine must also be retained in the bladder for several hours to allow the reaction to take place.)

Protein - Indication by dipstick of persistent proteinuria should be quantified by 24-h urine studies.

Positive: Pyelonephritis, glomerulonephritis, Kimmelstiel-Wilson syndrome (diabetes), nephrotic syndrome, myeloma, postural causes, preeclampsia, inflammation and malignancies of the lower tract, functional causes (fever, stress, heavy exercise), malignant hypertension, CHF

Leukocyte Esterase

Test detects 5 WBC/hpf or lysed WBCs. When combined with the nitrite test, it has a predictive value of 74% for UTI if both tests are positive and a value of >97% if both tests are negative.

Positive:

UTI (false-positive with vaginal contamination)

Reducing Substances

Positive: Glucose, fructose, galactose, false-positives (vitamin C, salicylates, antibiotics, etc)

Urobilinogen

Positive: Cirrhosis, CHF with hepatic congestion, hepatitis, hyperthyroidism, suppression of gut flora with antibiotics

 

URINE SEDIMENT - Many labs no longer do microscopic examinations unless specifically requested or if evidence exists for an abnormal finding on dipstick test (such as positive leukocyte esterase).

Red Blood Cells (RBCs): Trauma, pyelonephritis, genitourinary tuberculosis (TB), cystitis, prostatitis, stones, tumors (malignant and benign), coagulopathy, and any cause of blood on dipstick test (See previous section on blood pH.)

White Blood Cells (WBCs): Infection anywhere in the urinary tract, TB, renal tumors, acute glomerulonephritis, radiation, interstitial nephritis (analgesic abuse)

Epithelial Cells: Acute tubular necrosis (ATN), necrotizing papillitis. (Most epithelial cells are from an otherwise unremarkable urethra.)

Parasites: Trichomonas vaginalis, Schistosoma haematobium infection

Yeast: Candida albicans infection (especially in diabetics, immunosuppressed patients, or if a vaginal yeast infection is present)

Spermatozoa: Normal in males immediately after intercourse or nocturnal emission

Crystals:

• Abnormal.

Cystine, sulfonamide, leucine, tyrosine, cholesterol

• Normal.

Acid urine: Oxalate (small square crystals with a central cross), uric acid. Alkaline urine: Calcium carbonate, triple phosphate (resemble coffin lids)

Contaminants: Cotton threads, hair, wood fibers, amorphous substances (all usually unimportant)

Mucus: Large amounts suggest urethral disease (normal from ileal conduit or other forms of urinary diversion)

Glitter Cells: WBCs lysed in hypotonic solution

Casts: The presence of casts in a urine localizes some or all of the disease process to the kidney itself:

• Hyaline Casts. (Acceptable unless they are "numerous"), benign hypertension, nephrotic syndrome, after exercise

• RBC Casts: Acute glomerulonephritis, lupus nephritis, SBE, Goodpasture's disease, after a streptococcal infection, vasculitis, malignant hypertension

• WBC Casts: Pyelonephritis

• Epithelial (Tubular) Casts: Tubular damage, nephrotoxin, virus

• Granular Casts: Breakdown of cellular casts, leads to waxy casts; "dirty brown granular casts" typical for ATN

• Waxy Casts: (End stage of granular cast). Severe chronic renal disease, amyloidosis

• Fatty Casts: Nephrotic syndrome, diabetes mellitus, damaged renal tubular epithelial cells

• Broad Casts: Chronic renal disease

SPOT OR RANDOM URINE STUDIES - The so-called spot urine, which is often ordered to aid in diagnosing various conditions, relies on only a small sample (10-20 mL) of urine.

Spot Urine for 2-microglobulin - A marker for renal tubular injury

• Normal: <0.3 mg/L

• Increased: Diseases of the proximal tubule (ATN, interstitial nephritis, pyelonephritis), drug-induced nephropathy (aminoglycosides), diabetes, trauma, sepsis, human immunodeficiency virus (HIV), lymphoproliferative and lymphodestructive diseases

Spot Urine for Electrolytes - The usefulness of this assay is limited because of large variations in daily fluid and salt intake and the results are usually indeterminate if a diuretic has been given.

• Sodium <10 mEq/L (mmol/L): Volume depletion, hyponatremic states, prerenal azotemia (CHF, shock, etc), hepatorenal syndrome, glucocorticoid excess

• Sodium >20 mEq/L (mmol/L): SIADH, ATN (usually >40 mEq/L), postobstructive diuresis, high salt intake, Addison's disease, hypothyroidism, interstitial nephritis

• Chloride <10 mEq/L (mmol/L): Chloride-sensitive metabolic alkalosis (vomiting, excessive diuretic use), volume depletion

• Potassium <10 mEq/L (mmol/L): Hypokalemia, potassium depletion, extrarenal loss

Spot Urine for Erythrocyte Morphology

The morphology of red blood cells in a sample of urine that tests positive for blood may give some indication of the nature of the hematuria. Eumorphic red cells are typically seen in cases of postrenal, nonglomerular bleeding. Dysmorphic red cells are more likely associated with glomerular causes of bleeding. Each reference lab has standards, but as a general rule, the presence of >90% dysmorphic erythrocytes in patients with asymptomatic hematuria indicates a renal glomerular source of bleeding, especially if associated with proteinuria and or casts (ie, IgA nephropathy, poststreptococcal glomerular, sickle cell disease or trait, etc). If 90% eumorphic erythrocytes or even "mixed" results (10-90% eumorphic erythrocytes) indicates a postrenal cause of hematuria requiring a complete urologic evaluation (ie, hypercalciuria, urolithiasis, cystitis, trauma, tumors, hemangioma, exercise induced, benign prostatic hypertrophy (BPH), etc).

Spot Urine for Microalbumin - Used to determine which patients with diabetes are at risk for nephropathy. Clinical albuminuria occurs at >300 g albumin/mg creatinine. Base test on two or three separate determinations over 6 mo. Diabetic patients with levels between 30-300 g have microalbuminuria and are usually initiated on angiotension conversion enzyme (ACE) inhibitor or angiotensin receptor blocker.

Normal <30 g albumin/mg creatinine

Spot Urine for Myoglobin

• Qualitative negative

• Positive: Skeletal muscle conditions (crush injury, electrical burns, carbon monoxide poisoning, delirium tremens, surgical procedures, malignant hyperthermia), polymyositis.

Spot Urine for Osmolality - Patients with normal renal function should concentrate >800 mOsm/kg (mmol/kg) after a 14-h fluid restriction; <400 mOsm/kg (mmol/kg) is a sign of renal impairment.

• 75-300 mOsm/kg (mmol/kg) - Varies with water intake

• Increased: Dehydration, SIADH, adrenal insufficiency, glycosuria, high-protein diet

• Decreased: Excessive fluid intake, diabetes insipidus, acute renal failure, medications (acetohexamide, glyburide, lithium)

Spot Urine for Protein: Normal <10 mg/dL (0.1 g/L) or <20 mg/dL (0.2 g/L) for a sample taken in the early AM

 

CREATININE AND CREATININE CLEARANCE

Normal:

Adult Male:

• Total creatinine: 1-2 g/24 h (8.8-17.7 mmol/d) C

• learance: 85-125 mL/min/1.73 m2

Adult Female:

• Total creatinine 0.8-1.8 g/24 h (7.1-15.9 mmol/d)

• Clearance 75-115 mL/min 1.73 m2 (1.25-1.92 mL/s/1.73 m2)

Child:

• Total creatinine (>3 years) 12-30 mg/kg/24 h

• Clearance 70-140 mL/min/1.73 m2(1.17-2.33 mL/s/1.73 m2)

Decreased: A decreased creatinine clearance results in an increase in serum creatinine usually secondary to renal insufficiency. See Chapter 4, for differential diagnosis of increased serum creatinine.

Increased: Early diabetes mellitus, pregnancy

Creatinine Clearance Determination

Creatinine clearance is one of the most sensitive indicators of early renal insufficiency. Clearances are ordered for patients with suspected renal disease and are useful for following patients who are taking nephrotoxic medications, (eg, gentamicin). Clearance normally decreases with age. A creatinine clearance of 10-20 mL/min indicates severe renal failure, and a clearance of <10 mL/min usually indicates the need for dialysis.

To determine a creatinine clearance, order a concurrent serum creatinine and a 24-h urine creatinine. A shorter time interval can be used, for example, 12 h, but remember that the formula must be corrected for this change and that a 24-h sample is less prone to collection error.

24-HOUR URINE STUDIES

A wide variety of diseases, most of them endocrine, can be diagnosed by assays of 24-h urine samples. The following information gives the normal values for certain agents and the conditions associated with changes in these values.

Calcium, Urine

Normal: On a calcium-free diet <150 mg/24 h (3.7 mmol/d), average calcium diet (600-800 mg/24 h) 100-250 mg/24 h (2.5-6.2 mmol/d)

Increased: Hyperparathyroidism, hyperthyroidism, hypervitaminosis D, distal renal tubular acidosis (type I), sarcoidosis, immobilization, osteolytic lesions (bony metastasis, multiple myeloma), Paget's disease, glucocorticoid excess, immobilization, furosemide

Decreased: Medications (thiazide diuretics, estrogens, oral contraceptives), hypothyroidism, renal failure, steatorrhea, rickets, osteomalacia

Catecholamines, Fractionated - Used to evaluate neuroendocrine tumors, including pheochromocytoma and neuroblastoma. Avoid caffeine and methyldopa (Aldomet) prior to test

Normal: Values are variable and depend on the assay method used. Norepinephrine 15-80 mg/24 h [Systeme International (SI): 89-473 nmol/24 h], epinephrine 0-20 mg/24 h [0-118 nmol/24 h], dopamine 65-400 mg/24 h [SI: 384-2364 nmol/24 h].

Increased: Pheochromocytoma, neuroblastoma, epinephrine administration, presence of drugs (methyldopa, tetracyclines cause false increases)

Cortisol, Free - Used to evaluate adrenal cortical hyperfunction, screening test of choice for Cushing's syndrome

Normal: 10-110 mg/24 h [SI: 30-300 nmol]

Increased: Cushing's syndrome (adrenal hyperfunction), stress during collection, oral contraceptives, pregnancy

Creatinine

 

Cysteine - Used to detect cystinuria, homocystinuria, monitor response to therapy

Normal: 40-60 mg/g creatinine

Increased:

• Heterozygotes = < 300 mg/g creatinine/day

• Homozygotes = > 250 mg/g creatinine

5-Hydroxyindoleacetic Acid (5-HIAA) - 5-HIAA is a serotonin metabolite useful in diagnosing carcinoid syndrome.

Normal: (2-8 mg [SI: 10.4-41.6] mmol/24-h urine collection)

Increased: Carcinoid tumors (except rectal), certain foods (banana, pineapple, tomato, walnuts, avocado), phenothiazine derivatives

Metanephrines - Detects metabolic products of epinephrine and norepinephrine, a primary screening test for pheochromocytoma

Normal: <1.3 mg/24 h (7.1 mmol/L) for adults, but variable in children

Increased: Pheochromocytoma, neuroblastoma (neural crest tumors), false-positive with drugs (phenobarbital, guanethidine, hydrocortisone, monoamine oxidase (MAO) inhibitors)

Protein -See also Urine Protein Electrophoresis2.

Normal: <150 mg/24 h (<0.15 g/d)

Increased: Nephrotic syndrome usually associated with >4 g/24 h

17-Ketogenic Steroids (17-KGS), (Corticosteroids)

Overall adrenal function test, largely replaced by serum or urine cortisol levels

Normal:

Males 5-24 mg/24 h (17-83 mmol/24 h)

Females 4-15 mg/24 h (14-52 mmol/24 h)

Increased: Adrenal hyperplasia (Cushing's syndrome), adrenogenital syndrome

Decreased: Panhypopituitarism, Addison's disease, acute steroid withdrawal

17-Ketosteroids, Total (17-KS) - Measures dehydroepiandrosterone (DHEA), androstenedione (adrenal androgens); largely replaced by assay of individual elements

Normal:

Adult males 8-20 mg/24 h (28-69 mmol/L)

Adult female 6-15 mg/dL (21-52 mmol/L).

Note: Low values in prepubertal children

Increased: Adrenal cortex abnormalities (hyperplasia [Cushing's disease], adenoma, carcinoma, adrenogenital syndrome), severe stress, adrenococorticotropic hormone (ACTH) or pituitary tumor, testicular interstitial tumor and arrhenoblastoma (both produce testosterone)

Decreased: Panhypopituitarism, Addison's disease, castration in men

Vanillylmandelic Acid - Vannillylmandelic acid (VMA) is the urinary product of both epinephrine and norepinephrine; good screening test for pheochromocytoma, also used to diagnose and follow up neuroblastoma and ganglioneuroma

Normal: <7-9 mg/24 h (35-45 mmol/L)

Increased: Pheochromocytoma, other neural crest tumors (ganglioneuroma, neuroblastoma), factitious (chocolate, coffee, tea, methyldopa)

Drug Abuse Screen - Tests urine for common drugs of abuse, often used for employment screening for critical jobs. Assay will vary by facility and may include tests for amphetamines, barbiturates, benzodiazepines, marijuana (cannabinoid metabolites), cocaine metabolites, opiates, phencyclidine.

• Normal = negative

Xylose Tolerance Test (D-Xylose Absorption Test)

5 g xylose in 5-h urine specimen after 25 g oral dose of xylose or 1.2 g after 5-g oral dose Collection: Patient is nil per os [nothing by mouth] (NPO) after midnight except for water. After voiding at 8 AM, 25 g of D-xylose (or 5 g if gastrointestinal (GI) irritation is a concern) is dissolved in 250 mL water. An additional 750 mL water is drunk and the urine collected for the next 5 h.

Used to assess proximal bowel function; differentiates between malabsorption due to pancreatic insufficiency or intestinal problems.

Decreased: Celiac disease (nontropical sprue, gluten-sensitive enteropathy), false decrease with renal disease

URINARY INDICES IN RENAL FAILURE - Use Table 6-1 to help differentiate the causes (renal or prerenal) of oliguria. (See also Oliguria and Anuria.)

Urinary Indices Useful in the Differential Diagnosis of Oliguria:

URINE OUTPUT - Although clinical situations vary greatly, the usual, minimal acceptable urine output for an adult is 0.5-1.0 mL/kg/h (daily volume normally 1000-1600 mL/d).

URINE PROTEIN ELECTROPHORESIS - See Protein Electrophoresis, Serum and Urine.