Urinalysis in Clinical Practice

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Methods for Measurement of Specific Gravity. • By hydrometer: ... better than a urinalysis reported by a clinical chemistry laboratory. ... diagnosis of renal tubular acidosis (RTA). .... may occur with hemolysis, but free myoglobin is seldom present in a ..... Fogazzi GB, Verdesca S, Carigali G. Urinalysis: Core Curriculum 2008.

Section 17 Nephrology

Chapter

127

Urinalysis in Clinical Practice

Sekhar Chakraborty

INTRODUCTION Examination of urine is an indispensable part of evaluation of patients with impaired kidney function, particularly proteinuria, hematuria, urinary tract infection, nephrolithiasis and other renal or nonrenal diseases. The relatively simple chemical test performed in the routine urinalysis rapidly provides important information about primary kidney disorder and systemic diseases. Examination of urine sediment provides valuable information about renal parenchyma. Dipstick test can be automated and there is no substitute for careful examination of urine under the microscope. Experience in examining the urine is valuable; studies show that a urinalysis performed by an experienced nephrologist or trained physician is more likely to be better than a urinalysis reported by a clinical chemistry laboratory.

SPECIMEN COLLECTION AND HANDLING Urine should be collected with minimum contamination. • Clean catch midstream collection is performed • If not feasible, bladder catheterization is appropriate for adults— risk of contracting a urinary tract infection is negligible for a single catheterization • Suprapubic aspiration is used in infants • High urine osmolality and low pH favor cellular preservation, hence first voided morning urine is preferred • Chemical composition of urine changes with standing and formed elements degrade over time. Hence, urine is best examined when fresh but a brief period of refrigeration is acceptable • Bacteria in urine multiply at room temperature, hence bacterial counts from unrefrigerated urine are unreliable (Table 1).

ROUTINE URINALYSIS Appearance Selected substance that may alter the physical appearance or odor of the urine has been shown in Table 2.

Specific Gravity Weight of urine of measured volume Specific gravity = _____________________________________ Weight of distilled water of some volume Urine specific gravity is inaccurate surrogate for osmolality. Urinary specific gravity is usually between 1.001 and 1.035 and urine osmolality is usually between 50–1,000 mOsm/kg.

TABLE 1 │ Routine urinalysis Appearance Specific gravity Chemical tests (Dipstick) • pH • Protein • Glucose • Ketones • Blood • Urobilinogen • Bilirubin • Nitrites • Leukocyte esterase • Microscopic examination (formed element). Crystals

Urate, calcium phosphate, oxalate or carbonate, triple phosphate, cysteine, drugs

Cells

Leukocytes, erythrocytes, renal tubular cells, oval fat bodies, transitional epithelium, squamous cell

Casts

Hyaline, granular, red blood cell (RBC), white blood cell (WBC), tubular cell, degenerating cellular, broad, waxy, lipid-laden

Infecting organism

Bacteria, yeast, trichomonas, nematodes

Miscellaneous

Spermatozoa, mucous threads, fiber, starch, hair and other contaminants

Specific gravity near 1.010 connotes isosthenuria, with a urine osmolality same that of plasma.

Methods for Measurement of Specific Gravity • By hydrometer: Sufficient volume of urine required. • By refractometer: Calibrated in specific gravity units, a drop of urine is required. • By dipstick: Small amount of urine is required.

Clinical Importance of Measuring Specific Gravity • In the absence of proteinuria, glycosuria or iodinated contrast administration, a specific gravity more than 1.018 implies preserved concentrating ability of kidneys. • Measurement is useful to differentiate prerenal azotemia and acute tubulointerstitial nephritis (ATIN).

Chapter 127  Urinalysis in Clinical Practice

Section 17

TABLE 2 │ Selected substance that may alter the physical appearance or odor of the urine Color change

Substance

White

Chyle, pus, phosphate crystals

Pink/red/brown

Erythrocytes, hemoglobin, myoglobin, porphyrins, beets, senna, cascara, levodopa, methyldopa, deferoxamine Phenolphthalein and congeners, food colorings, metronidazole, phenacetin, anthraquinones, doxorubicin Phenothiazines

Yellow/orange/brown

Bilirubin, urobilin, phenazopyridine urinary analgesics, senna, cascara, mepacrine, iron compounds, nitrofurantoin, riboflavin, rhubarb, sulfasalazine, rifampin, fluorescein, phenytoin, metronidazole

Brown/black

Methemoglobin, homogentisic acid (alkaptonuria), melanin (melanoma), levodopa, methyldopa

Blue/green, green/brown

Biliverdin, pseudomonas infection, dyes (methylene blue and indigo carmine), triamterene, vitamin B complex, methocarbamol, indicant, phenol, chlorophyll, propofol, amitriptyline, triamterene

Purple

Infection with Escherichia coli, pseudomonas, enterococcus, others

Odor

Substance or condition

Sweet or fruity

Ketones

Ammoniacal

Urea splitting bacterial infection

Maple syrup

Maple syrup urine disease

Musty or mousy

Phenylketonuria

“Sweet feet”

Isovaleric or glutamic acidemia or excess butyric or hexanoic acid

Rancid

Hypermethioninemia, tyrosinemia

Chemical Composition of Urine

TABLE 3 │ Protein composition of normal urine

Routine Dipstick Methodology

Plasma proteins

Excretion (mg/day)

Albumin

12

Immunoglobulin G

3

Immunoglobulin A

1

Immunoglobulin M

0.3

Light chains κ λ

2.3 1.4

β-microglobulins

0.12

Other plasma proteins

20

All plasma proteins

40

Proper tabs impregnated with chemical reagents are fixed to a plastic strip. Reagents are chromogenic altered with a chest, which is highly specific. Some interfering substance in urine or extremes of pH may alter the results. Physiologic urinary pH lies between 4.5 and 8. pH should be tested properly in freshly voided urine because: • Growth of urea splitting bacteria and loss of carbondioxide (CO2) raise the pH • Bacterial metabolism of glucose may produce organic acids and lowers the pH • These strips are not sufficiently accurate to be used for the diagnosis of renal tubular acidosis (RTA).

Protein Dipstick Method Protein indicator strips are buffered at an acid pH near their color change point; wetting them with a protein containing specimen indicates a color change. Protein reaction may be scored as follows: Trace = 5–20 mg/dL 1+ = 30 mg/dL 2+ = 100 mg/dL 3+ = 300 mg/dL 4+ = > 2,000 mg/dL Protein strips are highly sensitive to albumin but less so to globulins, hemoglobin or light chains.

Acid Precipitation Test: Turbidimetric Method • Urine that is negative by dipstick but positive with sulphosalicylic acid is highly suspicious for light chains. • Tolbutamide, high-dose penicillin, sulfonic acid and radiographiccontrast agents may yield false-positive turbidimetric reactions. • Protein indicator used for routine dipstick analysis is not sensitive enough to detect microalbuminuria.

Protein Composition of Urine Protein composition of normal urine is represented in Table 3. Causes of proteinuria according to pathophysiology are shown in Table 4.

Nonplasma proteins Tamm-Horsfall protein

40

Other nonrenal derived proteins