Urinalysis and other Renal Labs

What is Urinalysis (UA)?

“Urinalysis is the physical, chemical, and

microscopic examination of urine. It involves

a number of tests to detect and measure

various compounds that pass through the

urine.”

UA is the best way to physically examine

the kidney

http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/003579.htm

What is UA?

95 % water, 5 % solids

3 main components :

Water

Urea

NaCl

Urine color pigments urochrome + urobilin

Intensity of color parallels degree of contamination

Preparation

Clean catch: clean-voided midstream specimen into non-sterile

container External genitalia should be cleansed (at least in females)

Urine is a body fluid, and should be handled as such Lab examination should occur within 30-60 minutes if held at room temperature

Should be at least 10-15 ml in volume to investigate

Evaluation of un-spun urine (appearance, sp. gravity, chemical

testing)

Centrifugation (2000-3000 rpm for 3-5 minutes) Decant supernatant, resuspend sediment in the urine that remains on the sides of

the tube, and place a drop on a clean slide for microscopic evaluation of sediment

Indications for UA

Suspect or confirm Urinary Tract Infection (UTI)

Rule out primary renal disease

Rule out systemic disease with renal

manifestations

Assess complications of hypertension

Assess presence or amount of endogenous or

exogenous excreted substances

Components of the Basic UA

Color / appearance

Chemistries Protein

Glucose

Ketones

Bilirubin / urobilinogen

Hemoglobin / blood

Nitrite

Leukocyte esterase

Specific gravity

pH

Microscopic exam

Cells / casts

Bacteria

Other organisms

Crystals

Other Tests

Gram stain

Urine Culture

Acid-fast stain

Protein electrophoresis

Antigen detection (immunofluorescence)

Visual Inspection of Urine

Color: usually light to dark yellow, depending on

concentration of the urinary pigments urochrome,

urobilin, and uroerythrin Color can be altered by:

Disease

Drugs

Food

Appearance: Turbidity: Can be due to cells, bacteria, or mucous

Amorphous phosphates (white precipitate) in alkaline urine, or amorphous

urates (pink precipitate) in acid urine

Abnormal Colors in Urine

Red:

Heme pigment or hematuria, drugs and food can also affect

Brown:

Heme pigment--hemeglobin or myoglobin

Orange/Yellow:

Bilirubin, urobilin but also carrots, pyridium, nitrofurantoin

White:

Pyuria, phosphates, chyluria, propofol

Abnormal Colors in Urine

Blue/Green: Methylene blue, propofol, amitriptyline, pseudomonas

UTI)

Black Hemoglobinuria, ochronosis—alkaptonuria (due to

excretion of homogentisic acid)

Purple: Urinary tract infections in chronically catheterized pts,

with alkaline urine

Red or Brown Urine

Common causes are hemoglobin (either free or

contained in RBCs) and myoglobin

All will be heme positive on dipstick

Centrifugation of the urine differentiates whether the

pigment is:

Contained within cells (hematuria) or represents

hemoglobinuria or myoglobinuria

Heme negative red urine certain drugs, food dyes,

and abnormal metabolites

Red to Brown Urine: Heme-Neg Dipstick

Medications:

Doxorubicin, Chloroquine, Deferoxamine, Ibuprofen, Iron

sorbitol, Nitrofurantoin, Phenazopyridine,

Phenolphthalein, Rifampin

Food dyes:

Beets , Blackberries, Food coloring

Metabolites:

Bile pigments, Homogentisic acid, Melanin,

Methemoglobin, Porphyrin, Tyrosinosis, Urates (pink and

turbid)

Specific Gravity (SG)

SG is the ratio of urine density compared to a

water standard

Sp gravity = mass of Uvol/mass of equivalent dH2Ovol

SG indirectly measures renal concentrating ability

Normal range 1.003-1.035

Is measured by dipstick or refractometer

Specific Gravity – Falsely Elevated

Excretion of radiopaque contrast media

Excessive proteinuria (as in nephrosis or

diabetes)

Excessive glycosuria

Refrigerated urine

Diagnostic Clues From Urine Odor

Volatile acids responsible for normal urine

odor

Specific odors & diagnoses:

Acetone: Diabetic Ketoacidosis (DKA)

Ammonia : Infection with urea breakdown

Maple Syrup Urine Disease

Asparagus or garlic ingestion

Causes of Increased Turbidity

Urate crystals in acid urine

Phosphates in alkaline urine

RBC's

WBC's

Bacteria

Vaginal secretions

Fat globules

Urine pH

Range 4.6-8 ; normal =

6

Animal protein diet :

acid urine

Vegetable / fruit diet :

alkaline urineStones that develop in

acid urine: Uric acid Cysteine Calcium oxalate

Stones that develop in

alkaline urine:

Calcium phosphate

Calcium carbonate

Mg PO4

Protein Analysis

Normal urine contains small amounts of albumin &

globulin

Proteinuria exists if > 20 mg/dl Incidence 6 to 9 % in asymptomatic patients

Dipstick tests use tetrabromophenol blue indicator

system (yellow to green as concentration ↑)

React mainly with albumin

False positive with quaternary ammonia compounds &

phenazopyridine dyes

Sulfosalicylic Acid Test (SSA)

SSA detects all proteins in the urine

The acid denatures existing proteins and causes

them to come out of solution ↑ turbidity Useful for detecting immunoglobulin light chains

(multiple myeloma), especially where the albumin

dipstick is negative or trace

Radio-contrast agents can cause false positive results,

as can any substance precipitated by acid

(cephalosporins, penicillins, sulfonamides)

Glucose Analysis

Based on reduction of metal ions by glucose

False positive reactions due to : Hypochlorite or chlorine

Other sugars (galactose, lactose, fructose, maltose, as during

pregnancy)

Enzyme - based tests (glucose oxidase) are more

specific for glucose

Can have false negative results with ascorbic acid,

tetracycline, or high uric acid

Reading Glucose mg/dl

Negative 0

Trace 100

1+ 250

2+ 1000

3+ 2000

4+ >2000

Correlation of Urine Glucose Readings

Hemoglobin Analysis

Dipsticks for hemoglobin can detect 1-2 RBC per

hpf Detects heme protein: both hemoglobin and myoglobin

Uses pseudoperoxodase activity of Hgb to oxidize a

chromogen

Free Hgb gives uniform color; intact RBC give a

speckled pattern

False positive results can occur with alkaline urine,

contamination with oxidizing agents, presence of semen

Ketones

Choices are: Acetest, test tube, dipstick

All use reaction between acetoacetic acid &

nitroprusside to make a violet dye complex

Acetone reaction is < 5 % of color change

Beta-hydroxybutyrate not detected

Causes of False Positive Ketones

Levodopa

Phenolphthalein (in laxatives)

Insulin

Pyridium (phenazopyridine)

Phenformin

Phenylketonuria

Nitrate Analysis

Nitrites are absent from normal urine

Most UTI bacteria reduce urinary nitrates to nitrites

Dipstick uses aromatic amine & diazonium compound to

produce pink color in presence of nitrite

False negatives :

High urine flow (dilutional) ; Frequent or continuous (foley)

voiding

Ascorbic acid

Bacterial inhibition with antibiotics

Leukocyte Analysis

Any purple color on dipstick indicates > 5

WBC's/hpf

Detects intact & lysed WBC's + WBC casts

False negatives : Cephalexin, gentamicin, nitrofurantoin

Up to 97 % sensitivity & 90 % specificity for

culture - proven UTI's

Bacterial Counts

< 1000 colonies per/ml implies only

contamination

Counts > 1000 and < 100,000 per/ml may

imply infection

Counts > 100,000 / ml imply infection

Cellular Casts

Represents contents of renal tubules

discharged into urine

Cast types & associated diseases :

Broad, epithelial, fatty, granular, or waxy :

parenchymal renal disease

RBC : acute glomerulonephritis

WBC : pyelonephritis

Cellular Casts

RBC casts Usually represent significant glomerular disease

Can occur after very strenuous exercise

Hyaline casts Clear, colorless ; due to protein precipitation

Occurrence depends on urine flow, pH, degree of proteinuria

Granular casts Result from disintegration of cell material into particles

Form waxy casts when renal failure is advanced

Urinary Crystals

Normal crystals in acid pH: amorphous urates,

uric acid, calcium oxalate, sodium urate, hippuric

acid

Normal crystals in alkaline pH: amorphous

phosphate, triple phosphate, calcium phosphate,

ammonium biurate, calcium carbonate

Abnormal crystals in urine found in acid pH:

cystine, cholesterol, tyrosine , leucine, billirubin

Urine Electrolytes

Clinical situations where measurements useful :

Sodium

Volume depletion, acute oliguria, hyponatremia (R/O SIADH)

Chloride

Determine if metabolic alkalosis is chloride resistant or

sensitive

Potassium

Determine site of K+ loss in hypokalemia (if < 10 meq/liter,

implies GI tract as source)

Urine Culture

All children (age < 14) and all males

Women with history of : Immunocompromised

Renal abnormalities

Diabetes mellitus

Recent instrumentation and indwelling catheter

Prolonged Symptoms before seeking care

3 or more ( ? > 5 ) UTI's in last year

Recent pyelonephritis

Recent hospitalization

Renal Function Tests

Physiology of Creatinine

Is the breakdown product of creatine (the storage source for high-energy phosphate in muscle cells)

CPK acts to add high energy phosphate to creatine from ATP

Creatine-phosphate transfers the phosphate to re-make ATP when energy is needed for metabolism