Urinalysis

Christos Argyropoulos MD, PhD, FASNUniversity of New Mexico School of Medicine

URINALYSISTHE PISS PROPHETS

Reference (“normal”) values in UA •Color – Yellow (light/pale to dark/deep amber) •Clarity/turbidity – Clear or cloudy •pH – 4.5-8 •Specific gravity – 1.005-1.025 •Glucose - ≤130 mg/d •Ketones – None •Nitrites – Negative •Leukocyte esterase – Negative •Bilirubin – Negative •Urobilirubin – Small amount (0.5-1 mg/dL) •Blood - ≤3 RBCs •Protein - ≤150 mg/d •RBCs - ≤2 RBCs/hpf •WBCs - ≤2-5 WBCs/hpf •Squamous epithelial cells - ≤15-20 squamous epithelial cells/hpf •Casts – 0-5 hyaline casts/lpf •Crystals – Occasionally •Bacteria – None •Yeast - None

Urine color

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Odor• Infection, the most common cause of abnormal urine

• production of ammonia by bacteria.

• Ketones may cause a fruity or sweet odor.

• Other disease Associations

• Maple syrup urine disease (maple syrup odor),

• Phenylketonuria (mousy odor),

• isovaleric acidemia (sweaty feet odor),

• hypermethioninemia (fishy odor).

Urine pH• Detected by a double indicator (methy red and bromthymo

blue) to give a broad range of colors• When measured with electrodes, normal pH is 4.5 – 7.8• Reagents strips should not be trusted outside the range of

5.5 – 7.5• High upH (>7)may indicate either infection or overgrowth

(prolonged storage) with urea-splitting organisms• Alkalic pH is seen with diuretics, vomiting, gastric suction

and bicarbonate therapy• Acidic upH(<5) is commonly seen in systemic acidosis• upH> 5-5.5 in the setting of systemic acidosis →RTA

Measures of Relative Density: Specific Gravity

• Determined by the number and size of particles in the urine

• Reagent strip contains a polymer which is saturated with Hydrogen ions. These are displaced by urinary cations=>change in local pH– Glucose and Urea DO NOT affect reagent strip SG– Poor correlation between SG and Urine osmolality– SG is falsely high when UpH<6, falsely low when

UpH>7• Isosthenuria: fixed SG @ 1.010 – clue to CKD in

real life and the boards

Measures of Relative Density: Urine Osmolality

• Biomarker of ADH action on the distal tubule• Measured directly with an osmometer• Under regular conditions, one would expect

each 35-40 mOsm/kg to increase SG by 0.001• Proteinuria, mannitol, dextrans and

radiographic contrast may affect osmolality• Used to investigate disorders of concentration

and dilution (more to follow)

Bilirubin & Urobilinogen

• Only conjugated bilirubin passes into the urine• Test for bilirubin will be positive in obstructive

jaundice, but negative in hemolysis• Urine urobilinogen is often positive in

hemolysis• None of them are great tests for liver disease

despite the high analytic sensitivity of the reagent

Leukocyte Esterase and Nitrates

Leukocyte Esterase• Esterases are

endoleukocyte enzymes released upon cell lysis

• Colorimetric detection• False (+) when ↑ lysis (+LE

w/o WBCs on microscopy)– ↑ storage, ↓ SG, ↓ UpH– Think about storage

conditions when w/u bacteriuria

Nitrates• Requires the presence of

nitrate reducing bacteria• The strip actually detects

nitrite not nitrate• Conversion of nitrate to

nitrite requires at least 4 hours, so inadequate bladder retention can give false –ve results

Energy Substrate MetabolismGlucose• Highly sensitive test based

on an oxidative reaction• Glucose is not normally

present in the urine• Presence indicates that the

plasma glucose is above the threshold of renal reabsorption (180-250 mg/dl) OR interference with this process:– Proximal tubulopathies (e.g.

Fanconi s)– SGLT2 inhibitors

Ketones• Acetoacetate and acetate

detected with the nitroprusside reaction (reduction reaction)

• Beta hydroxybutyrate is not detected via this reaction (and this is 80% of ketones in human ketotic states)

• Urine ketones may be +ve when serum test is –ve (nowadays indicates starvation ketosis)– used in the 70s as part of self-

monitoring for diabetes (much cheaper than glucometer strips)

• Alcoholic KA and DKA will also give +ve urine tests

Heme group detection (hemoglobin and myoglobin)

• Peroxidase type of reaction catalyzed by the heme moiety of either compound

• High oxidative states (e.g. betadine) or bacteria with pseudoperoxidase activity (Eenterobacteriaciae, Staph, Strep) will cause +ve reactions

• Normally haptoglobin binds both in serum• Large hemolysis/rhabdomyolysis will cause spillover

in urine• Positive test in the absence of RBCs in microscopy

suggest either rhabdo or hemolysis

False (+) and False Negative UA

Am Fam Physician. 2005 Mar 15;71(6):1153-1162.

If a compound is detected via an oxidative reaction, then oxidative agents will cause +ve, reductive agents (e.g. ascorbic acid) false –ve results and vice versa

URINE MICROSCOPYMore than meets the eye

http://dx.doi.org/10.1053/j.ajkd.2007.11.039

All images from Core Curriculum Nephrology 2008

Pre-analytic considerations

• Elements will deteriorate rapidly so fresh fresh urine (within 2-5 mins of collection) should be examined

• A midstream specimen is preferred for examination

• 5-12 ml , centrifuged at 400 g(2000 rpm) x 5 min, remove supernatant by suction, pellet resuspended and specimen examined under phase contrast

Cells of the Urine Sediment

Renal Causes of Hematuria

Non Renal Causes of Hematuria

Hematuria Algorithm

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Hematuria and GU malignancy

Pretest probabilities Risk Factors for GU CA

Am Fam Physician. 2013 Dec 1;88(11):747-754

Types and clinical associations of casts in urine microscopy

Urinary crystals

Clinical Urine Microscopy Patterns

Figure 1

Isomorphic RBCs

Dysmorphic RBCs

AcanthocytesProximal tubular cells

Glomerular hematuria: 10-80% dysmorphic RBCs or > 5% acanthocytes

Proximal RTEC

Leukocytes

Urothelial cells

Transitional cells

Figure 2

Oval fat bodies (lipiduria as in nephrotic syndrome)

Figure 3

Fine granular casts

Waxy cast

RBC castRenal Tubular Epithelial cast

http://www.medical-labs.net/muddy-brown-granular-casts-2892/

Muddy Brown Cast (ATN/AKI)

Maltese cross (fatty cast under polarized light)

Fatty cast (bright-field microscopy)

Bilirubin cast

Uric acid crystals

Calcium Oxalate Crystals

Calcium Phosphate Crystals

Figure 4

Cholesterol crystals

Cystine (benzene shaped) crystals

Amoxycillin CrystalBenzene

Crystal

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