PROTEINURIA

Normal Urinary Protein

10mg/dL or <100mg/day (Stras.),<150 mg/day (Henry)

Mild/Minimal Proteinuria

< 1g/day

Clinical Proteinuria

30 mg/dL or greater (300mg/L)

Moderate Proteinuria

1 - 4 g/day

Large/Heavy Proteinuria

>4 g/day

PRERENAL (OVERFLOW) PROTEINURIA

• Conditions affecting the plasma before it reach the kidneys

• NOT indicative of actual renal diseases; often transient

• It is often NOT detected in routine UA since Reagent Strips primarily detect albumin

low-molecular weight plasma protein of Intravascular Hemolysis

free hemoglobin

low-molecular weight plasma protein of Muscle Injury/Atrophy

myoglobin (rhabdomyolysis)

low-molecular weight plasma protein of Infection and Inflammation

Increased APRs (Acute phase reactant)

low-molecular weight plasma protein of Multiple Myeloma

Increased Bence-Jones Protein 

BENCE-JONES PROTEIN (BJP)

• Immunoglobulin Light chain

• Seen in multiple myeloma - proliferation of Ig-

• Producing Plasma cells; detected by chemical methods

Immunoglobulin Light chain portion

kappa/lambda

BENCE-JONES PROTEIN (BJP) Tests

Serum Electrophoresis, Immunofixation Electrophoresis

BENCE-JONES PROTEIN (BJP) SCREENING TEST (rarely done) BJP coagulates/precipitates at what temperature? 

40 C to 60 C (Turbid)

BENCE-JONES PROTEIN (BJP) SCREENING TEST (rarely done) BJP dissolves at what temperature? 

100 C (clear)

RENAL PROTEINURIA (True Renal Disease)

GLOMERULAR PROTEINURIA

what is GLOMERULAR PROTEINURIA?

Glomerular filtration barrier is defective, allowing plasma proteins to enter ultrafiltrate

Diabetic Nephropathy

• Common in people with Type 1 and Type 2 DM

• Reduced glomerular filtration > Renal Failure

Diabetic Nephropathy Indicator?

MICROALBUMINURIA

In Diabetic Nephropathy it is NOT detected by routine chem UA

MICROALBUMINURIA

Albumin Excretion Rate (AER) unit

=in ug/min or mg/24 hours

Normal AER =

0 - 20 ug/min (0 to 30 mg/day)

Microalbuminuria =

20 - 200 ug/min (30 to 300mg/day)

Clinical Albuminuria =

>200 ug/min (POS+ in chem strip)

MICRAL TEST

A strip employing antibody-enzyme conjugate that binds albumin.

MICRAL TEST Principle?

Enzyme Immunoassay

MICRAL TEST Sensitivity?

0 - 10 mg/dL

MICRAL TEST Reagents?

Gold-Labeled antibody, B-galactosidase, Chlorophenol Red galactoside

MICRAL TEST can cause false negative?

Dilute Urine

MICRAL TEST time and specimen?

60 seconds; First morning Urine

MICRAL TEST Positive Result?

RED/PINK color

MICRAL TEST Negative Result?

WHITE

IMMUNODIP

• Similar to a pregnancy test kit; container dipped for 3 minutes.

• Strips are packaged individually in special containers

IMMUNODIP principle?

immunochromatographic

IMMUNODIP senstivity?

1.2-8.0 mg/dL

IMMUNODIP Reagents?

Antibody-coated blue latex particles

ImmunoDip Reporting (Use First Morning Urine): Positive Result

Darker Top Band (2.0 - 8.0 mg/dL)

ImmunoDip Reporting (Use First Morning Urine): Borderline Result

Equal Band Color (1.2 - 1.8 mg/dL)

ImmunoDip Reporting (Use First Morning Urine): Negative Result

Darker bottom band (<1.2mg/dL)

ALBUMIN: CREATININE RATIO principle?

Sensitive albumin tests related to creatine concentration to correct for patient hydration

ALBUMIN: CREATININE RATIO sensitivity?

Albumin = 10 - 150 mg/dL

Creatinine = 10 - 300 mg/dL (0.9 - 26.5 mmol/L)

ALBUMIN: CREATININE RATIO Interference?

Visibly bloody or abnormally colored urine

ALBUMIN: CREATININE RATIO Reagents

Albumin and Creatinine

ALBUMIN: CREATININE RATIO Reagents Albumin name

diiodo-dihydroxy dinitrophenyl tetrabromosulfonphthalein

ALBUMIN: CREATININE RATIO Reagents Creatinine name?

Copper Sulfate (CuSO4), Tetramethylbenzidine (3,3',5,5'-TMB), Diisopropylbenzenedihydroperoxide (DBDH)

ALBUMIN: CREATININE RATIO FALSE positive

Cimetidine (similar to Creatinine)

REAGENT STRIP REACTIONS: CREATININE

Used by Automated Analyzers to calculate for A:C Ratio

REAGENT STRIP REACTIONS: CREATININE principle?

pseudoperoxidase activity of copper-creatinine complex (almost same princple of blood)

REAGENT STRIP REACTIONS: CREATININE color?

Orange to Blue

REAGENT STRIP REACTIONS: CREATININE reagent?

CuS04, TMB (chromogen), DBDH (peroxide)

REAGENT STRIP REACTIONS: CREATININE sensitivity?

• 10 to 300 mg/dL (0.9 - 26.5 mmol/L)

• Unable to detect the absence of creatinine

REAGENT STRIP REACTIONS: CREATININE REPORTING?

10, 50, 100, 200, 300 mg/dL (0.9, 4.4, 8.8, 17.7, 26.5 mmol/L) of Creatinine

REAGENT STRIP REACTIONS: CREATININE INTERFERENCES?

False Increase = Visibly Bloody Urine, Presence of Gastric Acid-Reducing Medication Cimetidine (Tagamet), Abnormally colored urine

Orthostatic/ Cadet /Postural Proteinuria

• A persistent, benign proteinuria; seen in young adults

• Occurs after periods spent in a vertical posture (standing)

• Increased pressure on the renal vein causes renal congestion and glomerular changes.

• Patients are requested to empty the bladder before going to bed; collect immediately after waking up

• Collect a second sample after standing for several hours

• Monitored every 6 months and re-evaluated as necessary

PRIMARY GLOMERULAR DISEASES

Glomerulonephritis, Glomerulosclerosis, Minimal Change Disease

GLOMERULAR DAMAGE DUE TO?

Poststreptococcal glomerulonephritis (immune complexes), DM, Lupus (SLE), Sickle Cell Anemia, Transplant Rejection, Infectious Diseases (Malaria, HBV, Endocarditis), Cancers (Leukemia, Lymphoma), Drugs (Lithium, Penicillamine), Toxins (Heavy Metals), Preeclampsia (Increased BP in pregnant women)

TRANSITORY GLOMERULAR CHANGES

Strenuous exercise, Fever, Dehydration, Hypertension, Postpartum Period, Extreme Cold Exposure

TUBULAR PROTEINURIA

• defective tubular reabsorption of protein (albumin)

• Originally discovered in workers exposed to cadmium dust (a heavy metal)

COMMON CAUSES OF TUBULAR PROTEINURIA

• Fanconi Syndrome (usually in PCT)

• Toxic Agents/Heavy Metals, Transplant Rejection, Poisons

• Acute/Chronic Pyelonephritis

• Severe Viral Infections

• Interstitial Nephritis

• Systemic Diseases - Sarcoidosis, SLE, Cystinosis, Galactosemia,

• Renal Tubular Acidosis, Renal Tuberculosis

• Wilson's Disease

• Hemoglobinuria (Hemolytic Disorders)

• Drugs (Aminoglycosides, Sulfonamides, Penicillin, Cephalosporins)

• Myoglobinuria (Muscle Injury)

• Strenuous Exercise

POSTRENAL PROTEINURIA

Urine includes proteins produced by the urinary tract or the urine is contaminated with proteins during excretion

POSTRENAL PROTEINURIA Proteins present?

Pus, Menstrual Blood, Hemorrhoidal Blood, Vaginal Secretions, Prostatic Secretions

COMMON CAUSES OF POSTRENAL PROTEINURIA

• Inflammation, Lower urinary tract infections

• Prostatic fluid/spermatozoa, Vaginal Secretions

• Injury/Trauma disorders, Malignancy

• Contamination during urination (menstrual contam.)

SULFOSALICYLIC ACID (SSA) PRECIPITATION TEST (aka EXTON'S TEST)

• Cold precipitation test that reacts EQUALLY with all forms of protein. NOT a confirmatory for reagent strip method.

• All ppt tests must be performed on centrifuged specimen

• Incubate for 10 minutes and invert tube twice

SULFOSALICYLIC ACID (SSA) reagents?

Exton's Reagent (3% SSA or 7% SSA)

Exton's Reagent 3% SSA composed of?

3mL of 3% SSA + 3mL centrifuged Urine

Exton's Reagent 7% SSA composed of?

3mL of 7% SSA + 11 mL centrifuged Urine (7/11 HAHAHAH)

SULFOSALICYLIC ACID PRECIPITATION GRADING turbidity of grade negative

• No Turbidity or increase in turbidity

• When tube is viewed from the top, a circle is visible in the bottom of the test tube (Brunzel 5th Edition)

SULFOSALICYLIC ACID PRECIPITATION GRADING turbidity of grade trace

• Perceptible/Noticeable Turbidity

• When the tube is viewed from the top, a circle is NOT visible in the test tube bottom. (Brunzel 5th Edition)

• Can read newsprint through mixture

SULFOSALICYLIC ACID PRECIPITATION GRADING turbidity of grade 1+

• Distinct turbidity WITHOUT discrete granulation

• Cannot read newsprint through mixture (Brunzel 5th Edition)

SULFOSALICYLIC ACID PRECIPITATION GRADING turbidity of grade 2+

Turbidity WITH granulation; NO flocculation

SULFOSALICYLIC ACID PRECIPITATION GRADING turbidity of grade 3+

Turbidity WITH granulation; AND flocculation

SULFOSALICYLIC ACID PRECIPITATION GRADING turbidity of grade 4+

Large clumps of precipitate or a solid mass

SULFOSALICYLIC ACID PRECIPITATION GRADING range negative

Range (mg/dL)

[Strasinger] <6

[Henry] ~ 5 or less

[Brunzel] <5

SULFOSALICYLIC ACID PRECIPITATION GRADING range trace

Range (mg/dL)

[Strasinger] 6-30

[Henry] ~ 20

[Brunzel] 5-20

SULFOSALICYLIC ACID PRECIPITATION GRADING range 1+

Range (mg/dL)

[Strasinger] 30-100

[Henry] ~ 50

[Brunzel] 30

SULFOSALICYLIC ACID PRECIPITATION GRADING range 2+

Range (mg/dL)

[Strasinger] 100-200

[Henry] ~ 200

[Brunzel]  100

SULFOSALICYLIC ACID PRECIPITATION GRADING range 3+

Range (mg/dL)

[Strasinger] 200-400

[Henry]  ~500

[Brunzel]  300

SULFOSALICYLIC ACID PRECIPITATION GRADING range 4+

Range (mg/dL)

[Strasinger] >400

[Henry]  ~ 1.0 g/dL

[Brunzel]  ≥500