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23 Laboratory Assessment of Kidney and Urinary Tract Disorders
Urinalysis
Urinalysis is an integral part of the evaluation of kidney and urinary tract disease. It consists of two components:
- Macroscopic examination. This includes dipstick evaluation, which yields information regarding the physical and chemical properties of a urine sample, whereas microscopy provides for evaluation of formed elements in the urine.
- Microscopic evaluation. A microscopic evaluation of urine sediment should be performed in the presence of abnormal renal function, hematuria or proteinuria on macroscopy, or clinical concern for urinary tract infection. This analysis should be done personally instead of relying on the laboratory technologist report.
MACROSCOPIC EXAMINATION OF THE URINE
Specimen Collection and Testing Procedure
- Urine samples should be examined within 2 hours of collection, as urea breakdown into ammonia results in alkaline urine, which promotes cell lysis and cast degradation.
- Ideally, samples should be collected from midstream catch of an early-morning specimen. Alternatively, bladder catheterization, either transurethral or suprapubic, may be used, although it may cause hematuria. There is no proven benefit of cleaning the genitalia prior to the collection.
- First perform dipstick testing to interpret colorimetric reaction results. It is important to assess the color and clarity of urine as well.
- For microscopic evaluation, collect 10 to 15 mL of a freshly voided specimen and centrifuge at 1,500 to 3,000 rpm for 5 minutes. Most of the supernatant is then discarded and the sediment resuspended in the remaining fluid. Remove approximately 0.5 mL of supernatant using a pipette and apply one drop of this solution onto a clean glass slide and cover with a cover slip. View the sample with phase-contrast microscopy at 100× and 400× magnification to examine the formed elements in the urine.
Physical and Chemical Properties of Urine
Color
- Normal urine should appear pale yellow in color. Dilute specimens are lighter in color, and concentrated urine has an amber appearance.
- Red urine is seen with hematuria, hemoglobinuria, myoglobinuria, and porphyrinuria. The presence of blood on dipstick testing without red blood cells (RBCs) on microscopy is suggestive of myoglobinuria. Consumption of certain foods (beets, rhubarb, and blackberries) and drugs (phenytoin and rifampin) may also color the urine red.1
- Brown urine may be seen with fava beans, chloroquine, nitrofurantoin, levodopa, metronidazole or with jaundice.1
Clarity
- Normal urine is clear but turns turbid with any urine particles.
- Turbid urine is seen with organisms, cells, and casts in the urine. Urinary tract infections usually produce turbid urine.
- Other causes include hematuria, lipiduria, and metabolic disease (oxaluria, uricosuria).
Odor
- Normal urine does not have a strong odor.
- Foul-smelling urine may be encountered with urinary tract infections due to ammonia production.1
- Diabetic ketoacidosis is associated with fruity odor, and gastrointestinal-vesical fistulas may result in a fecal odor to urine.1
Specific Gravity
- Specific gravity refers to the relative density of urine with respect to water.
- Normal values range from 1.005 to 1.020.
- Specific gravity ≥1.020 is consistent with concentrated urine in the setting of volume depletion; higher values may suggest glycosuria or other osmotically active substances in the urine such as contrast material.1
- Values ≤1.005 suggest dilute urine, which may be seen in water intoxication and diabetes insipidus.
- A fixed specific gravity of 1.010 is often seen in intrinsic renal disease where the kidneys can neither concentrate nor dilute the urine. As a result, the urine is isosthenuric (i.e., it has the same osmolality as serum).
- Proteinuria (>7 g/dL) may cause falsely elevated specific gravity, and falsely decreased values may be seen with urine pH <6.5.
Urine pH
- The normal urine pH ranges from 4.5 to 8.0.
- Acidic urine is associated with metabolic acidosis (e.g., starvation ketosis, diabetic ketoacidosis), dehydration, and large protein loads. Respiratory acidosis can lead to compensatory metabolic alkalosis and decreased urine pH. Extrarenal bicarbonate losses (e.g., diarrhea) may promote urinary acidification.
- Alkaline urine is typically seen in distal renal tubular acidosis. Urea-splitting organisms (e.g., Proteus spp.) can raise urinary pH. Similarly, prolonged storage of urine results in conversion of urea to ammonia, and urinary pH increases.
Glucose
- In patients with preserved renal function and serum glucose concentrations <180 mg/dL, urine glucose is typically absent as it is almost completely reabsorbed in the proximal tubule.
- Dipstick analysis can provide qualitative information regarding the presence or absence of glycosuria.
- Urine glucose may be seen in diabetes mellitus, liver disease, pancreatic disease, Fanconi syndrome, and Cushing syndrome.
Protein
- Urine dipstick is the main screening test for proteinuria.
- The test is a pH-based assay, and albumin is the primary protein identified.
- False-positive results may be seen with highly concentrated specimens, alkaline urine, phenazopyridine, or quaternary ammonia compounds. False-negative tests are associated with dilute urine and nonalbumin proteins, including immunoglobulins and tubular proteins.
- A sulfosalicylic acid test may be used to identify nonalbumin proteins.
- If the dipstick test is positive, the protein should be measured using either a 24-hour protein excretion or a random protein-to-creatinine ratio (PCR) if the creatinine is at a stable baseline.
Hemoglobin
- The dipstick can detect as few as four RBCs per high-power microscopic field (HPF).
- Free hemoglobin or myoglobin in urine, as can be seen with hemolysis or rhabdomyolysis, catalyzes the same dipstick reaction. These conditions should be suspected when the urine dipstick is positive for occult blood in the absence of RBCs on microscopic examination of the urine sediment.
- False-negative tests result from the presence of substances such as ascorbic acid (ingestion of >200 mg/day vitamin C) that diminish the oxidizing potential of the reagent strip.
- Detection of hematuria by dipstick should always be confirmed by microscopic examination of the urine. The presence of dysmorphic RBCs or RBC casts (a so-called active urine sediment) or the coexistence of proteinuria suggests that the hematuria is of glomerular origin.
Leukocyte Esterase
- The detection of leukocyte esterase relies on the release of esterases from lysed neutrophils.
- False-positive results are seen when significant delay occurs between sampling and testing and when the sample is contaminated by vaginal cells.
- False-negative results occur with inhibition of granulocyte function, including glycosuria, proteinuria, high specific gravity, and high urinary concentrations of certain antibiotics (tetracycline, cephalexin, gentamicin).
Urine Nitrite
- Urine dipstick testing depends on bacterial conversion of urinary nitrates into nitrite.1
- While many gram-negative bacteria can reduce nitrates to nitrite, certain organisms, including Enterococcus spp., Neisseria gonorrhoeae, Pseudomonas, and mycobacteria, do not; this may result in negative results.
- False-negative results are also seen with insufficient bladder incubation time, low consumption of nitrates (found in vegetables), and reduction of nitrates to nitrogen by bacteria.
- The test has low sensitivity but high specificity.
- Both leukocyte esterase and nitrite testing must be combined with microscopic examination and clinical context to accurately diagnose urinary tract infections.
MICROSCOPIC EXAMINATION OF URINE
Red Blood Cells
- Presence of three or more RBCs/HPF on two of three urine specimens is diagnostic of microscopic hematuria.1
- Dysmorphic RBCs and RBC casts are suggestive of glomerular disease, whereas normal RBCs suggest nonglomerular bleeding in the urinary tract.
- Hematuria is discussed in further detail in Chapter 25.
White Blood Cells
- Urinary white blood cells (WBCs) are associated with either infection or inflammation.
- Pyuria is defined as more than five WBCs/HPF.
- Extraurinary inflammation, as seen in appendicitis, can also result in pyuria.
- Urine eosinophils
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