Urine Analysis: Liquid biopsy of the urinary tract

By

DR. Ashraf Abdel-Basset Ass. Prof. in Pediatrics Mansoura Faculty of Medicine

 Pyuria
Hematuria Proteinuria

Crystaluria

Terminology
Pyuria:
> 10 cells/HPF of centrifuged urine sample.

Bacteriuria:
Bacteria in bladder urine. Growth of 100,000 colony-forming units (CFU) in freshly voided urine mostly used as the cutoff point between contamination and true bacteriuria.

Urinary tract infection (UTI):

Heterogeneous group of conditions in which there is growth of bacteria in the urinary tract.

Diagnosis of UTI
Urine culture.

Urine analysis.
Enzymatic tests. Others.

Diagnosis of UTI
Urine culture

Culture of properly collected specimen of urine

Diagnosis of UTI
Urine collection

No

urinary

control:

catheterization

or

suprapubic aspiration.
Urinary

control:

midstream

clean-catch,

catheterization, or suprapubic aspiration.

Diagnosis of UTI
Urine culture interpretation
Growth of single urinary pathogen
Methods of collection
Suprapubic aspiration

Quantitative culture: UTI present

Any number (the exception is up to 23x103 CFU/mL of coagulase-negative staphylococci). 50 x 103 CFU/mL. Infection may be present with counts from 10 x 103 to 50 x 103 CFU/mL. 105 CFU/mL. Asymptomatic patients: at least two specimens on different days with 105 CFU/mL of the same organism.

Catheterization

Midstream clean-void Midstream clean-void

Diagnosis of UTI
Urine analysis
Pyuria:

> 10 cells/HPF of centrifuged urine sample. Sensitivity: 89%. Varies with volume of sample, duration of centrifugation, volume of resuspension, observer error.

Bacteriuria: Gram stain.

Others: Hematuria, WBCs casts, alkaline urine.

Diagnosis of UTI
Enzymatic tests
Leukocyte esterase test:
Principle:

Detects esterase in neutrophils demonstrates the presence of pyuria.

Sensitivity:

10 leukocytes/mm3 52.9%. 20 leukocytes/mm3 66.7%.

Diagnosis of UTI
Enzymatic tests
Nitrite test:
Principle:

Nitrate

Bacteria 4h

Nitrite + dye Red azo.

Sensitivity:

29.2 - 44.9%

How to treat?
General measures
A. B. C.

Change pH of the urine. Water and fluid intake should be encouraged. Complete evacuation of the bladder especially before going to bed at night:

Frequent micturation.
Double or triple micturation.

Hematuria
Definitions
Dipstick:

Color change.

Microscopic:

Centrifuged sample:

RBCs > 5/HPF.

Uncentrifuged sample: RBCs > 5/mm3

Addis count > 240.00 RBCs in 12 hour urine.

Work Up

Exclusion of the other causes of discolored urine. Confirmation of the presence of hematuria.

Determination of the cause of hematuria:

1. 2. 3.

Thorough history taking.

Careful examination.
Investigation.

Work Up

Exclusion of other causes of discolored urine.

Confirmation of the presence of hematuria.

Determination of the cause of hematuria:
1. 2. 3.

Thorough history taking. Careful examination. Investigation.

Causes of discolored urine

Pink, red, tea-colored Disease states Ingestion

* Hemoglobinuria * Myoglobinuria * Porphyrinuria * Serratia marcescens * Bile pigments * Urates

* Aminopyrine * Anthrocyans * Azathioprine * Azo dyes * Beets * Benzene * Blackberries * Chloroquine * Desferroxamine * Rhodamine B

* Diphenylhydantoin * Ibuprofen * Lead * Methyldopa * Nitrofurantoin * Phenazopyridine * Phenolphthalein * Rifampin * Sulfasalazine

Causes of discolored urine

Dark brown, black
Disease states Ingestion

* Alkaptonuria * Homogentisic acid * Melanin * Methemoglobinuria * Tyrosinosis

* Alanine * Cascara * Resorcinol * Thymol

Work Up

Exclusion of other causes of discolored urine. Confirmation of the presence of hematuria. Determination of the cause of hematuria:
1. 2. 3.

Thorough history taking. Careful examination. Investigation.

Confirmation of the presence of hematuria

2-3 UA over 2-3 weeks period
Studied
Hematuria:

8954 children
364 (4.1%) 142 (1.6%)
Vehaskari et al., J Pediatr 95:676, 1979

1st sample 2nd sample

Bubbles on the surface of the urine are a sign of disease of the kidneys. Hippocrates

Proteinuria

Definitions:
< 4mg/m2/h < day > night

Normal

Proteinuria mg/24h

40% alb, 15% Igs,

40% T.H prt. 5% others

Proteinuria Definitions
Significant
Dipistick:

Trace: 10 mg/dl +3: 300 mg/dl

+1: 30 mg/dl +4: >1 g/dl.

+2: 100 mg/dl

Sulphosalicylic acid:

5ml of urine + 3 drops of 20% of the acid turbidity

Non-nephrotic: < 2 years: > 0.5 >2 years: > 0.2 Nephrotic: 3 Non-nephrotic Nephrotic 4-40 mg/m2/h > 40 mg/m2/h

Protein / creatinine ratio:

Quantitative:

Work Up
Exclusion of the other causes of +ve tests. Confirmation of the presence of proteinuria. Differentiation between different types of proteinuria. Determination of the cause of proteinuria.

Work Up
Exclusion of other causes of +ve tests.
Confirmation of the presence of proteinuria.

Differentiation

between

different

types

of

proteinuria.
Determination of the cause of proteinuria.

False +ve Tests for Proteinuria

Dipstick
Highly concentrated urine Highly alkaline buffered urine (pH>8) Gross hematuria Pyuria Skin cleanser chlorhexidine Quarternary ammonium compounds Phenazopyridine

Sulfosalicylic acid
Highly concentrated urine Gross hematuria Pyuria Radiologic contrast media High levels of penicillin, cephalosporins Metabolites of sulfonamide Tolbutamide Tolemtin

Work Up
Exclusion of other causes of +ve tests. Confirmation of the presence of proteinuria. Differentiation

between

different

types

of

proteinuria.
Determination of the cause of proteinuria.

Causes of Proteinuria
I- Transient: Fever, exercise-induced, congestive heart failure, exposure to cold, epinephrine infusion, seizures, emotional stress, ect. II- Orthostatic. III- Persistent:
A- Glomerular:
1- Congenital or hereditary. 2- Acquired: a- Primary or idiopathic. b- Secondary: 1- Infection 3- Drugs 5- Miscellaneous 1- Congenital or hereditary. 2- Acquired.

2- Multisystem 4- Neoplasm

B- Tubular:

C- Overload:
* Light chains * Myoglobin * Lysozyme * Hemoglobin

Orthostatic Proteinuria
2-5% of adolescents. Diagnosis:
7am-10pm 10pm-7am

Rarely >1g/24h urine. ? Hemodynamic changes.

+ve

-ve

Mild glomerular abnormalities in 50% of

cases. Prognosis is good.

Glomerular vs tubular
Glomerular Tubular

Quantity Dipsticks for prt. Ur prt electrophoresis Alb/B2 microglobulin (ng/mg) Tubular functions

Mild severe +ve Mainly albumin 1000-15,000 Normal

<1 g/day -ve LMW band <300 Abnormal

Evaluation of isolated proteinuria

Negative - Reassure - Routine medical follow-up

Initial positive dipstick test for urinary protein Obtain two additional urines

Two of three urines positive

Identifiable non-renal cause?
No

Additional evidence for renal disease

Yes No

Symptomatic Specific evaluation - CBC, ESR - BUN, Cr, electr., alb, total prt, chol. - Measurement of GFR - C3, C4, C3 - Streptozyme - ASO, Anti-Dnase B - ANA, anti-DNA - Renal imaging - Urine culture - Renal biopsy (consider)

Asymptomatic Orthostatic test

Persistent nonorthostatic proteinuria

Orthostatic proteinuria Repeat test in one year

Absent or intermittent proteinuria Repeat urinalysis in one month

Negative
No further evaluation

Positive
Continue follow up

UTI
Urine culture is the golden standard method

for the diagnosis of UTI

Acute pyelonephritis usually presents with

extrarenal manifestations especially in young infants.

All children with 1st documented UTI should

be evaluated by renal sonography

Hematuria
1 2
Exclude other causes of discolored urine Confirm the presence of hematuria Serious sings: Hypertension and or edema Proteinuria RBCs casts +ve family history of progressive renal disease

Proteinuria
1 2
Exclude causes of false positive test

Confirm the presence of proteinuria

Serious sings: Hypertension and or edema Hematuria +ve family history of progressive renal disease

Crystaluria

Many of the crystals found in urine are of limited

clinical significance except in:

Metabolic disorders

Calculus formation

Urine analysis is the liquid biopsy of the urinary tract