11, 12 Renal Function and Urinalysis

3 Basic Functions of the Kidneys

Excretion

Removal of waste products of metabolism

(urea, creatinine, UA)
Removal of inorganic substances ingested
(Na, K, Cl, Ca, PO4, Mg, SO4)

Regulation

Homeostatic control through reabsorption &

secretion to establish water & electrolyte balance in
all body fluid compartments

Homeostasis in acid & base levels, to maintain proper

body pH
Homeostasis in protein levels

Endocrine
Primary control over the production of

Renin (blood pressure)

Calcitrol (deposit/removal of Ca & P04 from bones)
Erythropoietin (RBC production)

Secondary site in degrading

Insulin (blood glucose control)
+
Aldosterone (Na regulation)
Urine Formation

3 processes: filtration, secretion, excretion

Each kidney: 500,000 nephrons

NB: Impairment of kidney function is detectable
if 80% of the nephrons are already destroyed
Urea

Creatinine
Uric Acid
Non-fasting specimens acceptable
Serum or plasma
Increased with
Increased with
Increased with
high protein diet severe exercise and severe exercise
high meat diet
Males have
Varies with age,
higher levels
gender and lean
body mass
Reference levels
increase with age
Renal Clearance Tests

Clearance of a substance by the kidney approximates

GFR

Definition: the amount of blood cleared of a

substance per unit time

Depends on: plasma level of the substance & excretion

rate of the kidney (which reflects GFR & RPF)
NB: Best to detect mild to moderate glomerular damage
Urea Clearance
not a reliable substance to determine GFR because it

is also reabsorbed & secreted in areas of the nephron

other than the glomerulus
Creatinine Clearance

Creatinine: an endogenous substance that may be

measured both in serum & urine

most commonly used: due to

convenience of an endogenous substance

routine methods available

plasma levels have very little daily variation

freely filtered & very small amount secreted in the

tubules

Inulin Clearance

Advantage: freely filtered, with no addition or

secretion in the nephron

May be measured in both serum & urine

Disadvantage: the necessity to administer inulin

intravenously (IV)
PAH Clearance
Advantage: high extraction rate from the blood, as it

is both filtered & secreted by the kidney

Disadvantage: gives an accurate assessment only if

the kidney is functional
Tubular Function Tests

Ability of the tubules to reabsorb & secrete

substances during urine formation
Phenolsulfonphthalein

Exogenous substance

Injected IV
Amount secreted into urine is tested at 15 min

intervals

Results: reflects renal plasma flow & tubular

secretory function
Beta2-Microglobulin
protein is present in all nucleated cells

filtered but not normally reabsorbed

measurement of serum & urine levels serves as an

indicator of renal excretory functions
Concentration Tests
Osmolality
Measures the number of particles present per

unit of solution
Unit: mOsm/kg H2O (50-1,200)

Depends on patients hydration

Serum:urine (between 1:1 and 1:3)

Concentrating ability of the kidney

Specific Gravity
Included in routine urinalysis

Reference range: 1.003 1.030

NB: When concentrating ability of the kidney is impaired,

urine becomes isosthenuric, having the same specific
gravity as the original ultrafiltrate: 1.007 1.010
Nonprotein Nitrogenous Compounds (NPN)

All compounds containing nitrogen except protein

Mainly eliminated in the kidney

Urea (45%)
Creatine (1-2%)
AA & UA (20%)
Ammonia (0.2%)
Creatinine (5%)
BUN/Creatinine Ratio

A better indicator of the source of elevations of either

substance than the substance value alone
N.V. between 10:1 and 20:1
Decreased Ratio (less common than an increased ratio)

ATN

starvation

low protein intake

severe liver disease

severe diarrhea

renal dialysis
&/or vomiting
rainwater@mymelody.com || 1st semester, AY 2011-2012

Increased Ratio with Normal Creatinine

Dehydration
High protein diet

Increased protein catabolism

Muscle wasting
Reabsorption of blood proteins after GI bleeding

Tx with cortisol

Decreased perfusion of kidneys

(HF, shock, hemorrhage)
Increased Ratio with Elevated Creatinine
Nephrolithiasis

Prostatism

Tumors of genitourinary tract

Severe infection

Urine Specimens
st

1 morning specimen: most concentrated, best for

protein, microscopic examination
Random specimen: more convenient for patients,

suitable for screening purposes

Indispensable part of clinical pathology
Parameters for Routine Urinalysis

General description: gross appearance, color,

transparency, pH, specific gravity

Chemistry: protein & sugar [semi-quantitative]

Microscopic Examination of centrifuged urinary

sediment for: WBC, RBC, pus cells, epithelial cells,
bacteria, etc.

Normal Ratio with elevated Urea & Creatinine

End stage renal disease

Acute renal failure

Glomerular diseases

Acute nephritic syndrome

Rapidly progressive GN

CGN

NS

Tubular diseases (acute pyelonephritis)

Gross

Urinalysis

Microscopic

Routine Urinalysis
A series of routine tests done on urine for evaluation

of urinary & systemic disorders

Divided into 3 parts: gross, chemical, microscopic

Microscopic components in urine sediments

Cells RBC, WBC, epithelial cells

[squamous, transitional, renal tubular]

Casts hyaline, waxy, RBC, WBC, RTC, granular, etc.

Crystals urates, phosphates, oxalates, etc.

NB: Abnormal cells: tumor cells, viral inclusions, platelets,

bacteria, fungi, parasites, etc.

Purpose

Screening test for renal or urinary tract disease

To help detect metabolic or systemic disease
unrelated to renal disorder
To detect substances or metabolites excreted in the
urine [eg. drugs]
Evaluation of overall body function

Preparation
No food nor fluid restriction prior to the test

[but could affect some parameters]

Intake of some medication could affect some results

[color, pH, etc.]
Collection
Collect in a clean, dry container

Examine within 2 hours of voiding

(if delayed refrigerate or preserve)

Examinations:
routine, bacteriologic, quantitative analysis, etc.
Precautions

Send specimen to the laboratory immediately

Examination should be done ASAP

Refrigerate specimen if analysis will be delayed

longer than one (1) hour
Interfering Factors

Severe exercise may cause transient hemoglobinuria

Insufficient volume [<2mL] may limit range of

procedure
Delayed examination may limit some results

Food, drugs, hydration may alter normal parameters

Color straw to dark yellow

Odor mildly aromatic
Appearance clear
Sp. gr. 1.010 1.030 [1.015 -1.025]
pH 4.6 8.0 [5.5 6.5]

Chemical semi-quantitative
Protein negative to 4+ (++++)

Sugar negative to 4+ (++++)

Microscopic examination
RBC: 0-2/hpf

WBC: 0-5/hpf
EC: 0-5/hpf

Casts: none, [or 1-2 hyaline/cs]

Crystals: present
Bacteria, yeasts, parasites: none

Urobilinogen
Majority: reabsorbed

The remaining majority that is unabsorbed:

excreted in the feces [as urobilins or stercobilins]

Small amount: excreted in the urine

NR: 0.5-2.5 mg or units/24 hr
Myoglobinuria

In acute rhabdomyolysis [eg. Trauma] myoglobin is

released

Rapidly cleared from blood

Urine: red-brown

Seen in: severe exercise, marathon, karate

Hemoglobinuria

Indicates significant intravascular hemolysis

May follow severe exertion damage to small blood

vessels

Levels > 50 mg/dL : plasma appears pink

Hematuria

Diseases [neoplastic]

Trauma, calculi
Bleeding disorder

drugs [anticoagulants, cyclophosphamide]

rainwater@mymelody.com || 1st semester, AY 2011-2012

Abnormal Findings

Color: diet, drugs, disease, etc.

Odor: starvation, dehydration, infection

Turbidity: cells, bacteria, fats, etc.

Sp. gr. DI, ATN, infection, metabolic disorders

pH: infection, fever, metabolic disorders

Protein: RF, GN, NS, MM, etc.

Sugar: DM, pheochromocytoma, Cushings syndrome

Quantification of Proteinuria

Heavy proteinuria (>4g/day) classically seen in NS:

associated with glomerular dysfunction or damage
0
due to 1 renal disease or systemic illness

Moderate proteinuria (1.0-4.0 g/day) associated

with MM, toxic nephropathies

Minimal proteinuria (<1.0 g/day) chronic

pyelonephritis, nephrosclerosis, etc.

Quantitative Analysis

24-hr collection: for hormones, proteins, electrolytes,

creatinine

2-12 hr collection: xylose excretion, quantitative cell

counts

Types of Proteinuria
Functional Proteinuria

o
Not associated with systemic/renal damage

Severe muscular exertion

Pregnancy

Orthostatic proteinuria
Organic Proteinuria

o
Associated with demonstrable systemic or
renal pathology
Pre-renal - fever, toxic conditions, venous

congestion, renal hypoxia, hypertension,

myxedema, Bence Jones proteinuria
Renal - GN, NS, tumor, infection, infarct

Post-renal - pyelonephritis, ureteritis,

cystitis, urethritis, prostatitis

Bacteriologic Examination
Clean-voided, mid-stream catch

Catheterization or supra-pubic aspiration

Done immediately or refrigerate at 4 C

Normal: no growth (aerobic & anaerobic)
Appearance & Color
Colorless: polyuria, diabetes insipidus

Cloudy: phosphates, urates, WBC, bacteria,

yeasts, spermatozoa, dye

Milky: lipiduria, chyluria, neutrophils

Yellow-green: bilirubin-biliverdin
Red: hgb, mgb, beets, porphyrin

Brown-black: methgb, melanin, homogentisic a

Blue-green: Psa, chlorophyll, indicans

Normal: light yellow

pH

Test Methods for Protein

Heat & acetic acid

Sulfosalicylic acid

Dipstick

Normal: 5.5-6.5 [4.5-8.0]

> 6.0 - alkalosis, Proteus infection

Poison (carbonic acid inhibitors)

Long standing at room temp

(due to bacterial growth)
Methods: pH meter, dipstick

Specific Gravity

Estimate of relative density

Proportion of dissolved solids in a defined volume of

solvent
Methods: hydrometer, refractometer, dipstick

Normal range: 1.010-1.030 (1.015-1.025)

Normally, small amount of small molecular weight

protein filter through
Small fraction is reabsorbed by the tubules,
remainder excreted (up to 0.1gm/24 hr)
normal: negative

Qualitative Categories of Proteinuria

Glomerular pattern heavy proteinuria

Tubular pattern light proteinuria

[B-globulin, light chain Ig, B2 microglobulin]

Overflow proteinuria excess level of protein in the

circulation [Hgb, Mgb, Ig]

Bence-Jones proteinuria MM, lymphomas

Microalbuminuria

The presence of albumin in the urine above

normal level but below the detectable
range of conventional dipstick method

Normal threshold: 180mg/100mL

Normal: negative
Causes of glucosuria

1.

Glucosuria with hyperglycemia

Diabetes mellitus

Increased intracranial pressure

E.g., tumors, intra-cerebral hm, skull fracture
Endocrine diseases: Cushings syndrome,

pheochromocytoma

Occasionally & transiently, after MI

After certain types of anesthesia (e.g., ether)

2.

Glucosuria without hyperglycemia

Glucosuria of pregnancy
Renal glucosuria

Inborn errors of metabolism

e.g., Fanconis syndrome

Nephrotoxic chemicals
e.g., CO, lead, mercuric chloride

Protein

24-hr measurement
Microalbumin

Glucose

Methods

Clinistix (o-toluidine chromogen)

Multistix (KI chromogen)
Chemstrip (aminopropyl-carbazol)

Other sugars
Fructose inherited enzyme deficiency

Galactose galactose metabolism

Lactose in normal pregnancy & lactation

Pentose ingestion large amount of fruits

Sucrose ingestion of large amount

Test Methods for Glucose
Benedicts test

Glucose oxidase
rainwater@mymelody.com || 1st semester, AY 2011-2012

Tests for Diabetes

Types of Diabetes
Type I DM (Insulin Dependent)

Begins early in life

More severe
Require insulin for management

Show severe insulin deficiency on blood insulin assay

Type II DM (Non-Insulin Dependent)

Begins in middle age or afterward

Associated with overweight body status

Less severe blood glucose abnormality

Can be treated by diet alone, oral medications or

small doses of insulin
Methods of Blood Glucose assay
Biochemical
1. Non-specific methods
eg. Folin-Wu
2. Non-specific but more accurate
eg. Nelson-Somogyi, orthotoluidine, ferricyanide
3. Enzymatic
eg. glucose oxidase, hexokinase
Paperstrip method (bedside method)
1. Dextrostix
2. Visidex
3. Chemstrip

Old Classification
Overt diabetes
Latent diabetes
Sub-clinical DM
Pre-diabetes
Diabetes of pregnancy

OGTT criteria for children

Child with classic symptoms

Upper limit of FBS: 130 mg/100 ml

Glucose dose calculated based on weight

Gestational Diabetes

Abnormal glucose tolerance with onset or recognition

of pregnancy (not before)
Screening test FBS plus 2 hr PPBG

Diagnostic test OGTT [load: 100 g glucose]

th
NB. Extraction up to 4 hour
Glycosylated Hgb

Hgb A1C (6-7%) glucose attaches to the terminal valine

of the globin beta chain

Occurs during the exposure of RBCs to plasma glucose

Represents the average level of blood glucose in the

preceding 2-3 mos

Used to monitor effectiveness (long-term) diabetic

therapy, patients compliance
Pancreatic Diseases

Glucose Tolerance Test

In instances when insulin deficiency is small,
o
abnormality is noted only when an unusually heavy
CHO load is placed in a system
o
Factors affecting GTT: inactivity, obesity, fever, stress,
AMI, trauma, burns, advanced age
OGTT Requirements

3 days adequate carbohydrate diet

Fasting for 6-8 hr

Standard test doses:

75 g non-pregnant adult
100 g pregnant
Added to 300 mL water or lemon juice
NB: To be consumed within 5 min, timing starts when
patient starts drinking
OGTT Test Protocol

FBS (Fasting Blood Sugar), 1 hr, 2 hr, 3 hr

OGTT Interpretation
Plasma Glucose Level
OGTT
Normal
Fasting
70-115
2 hr
<140
3 hr
70-115

Impaired Glucose Tolerance

New Classification
DM
Impaired GTT
Previous abnormal GT
Potential abnormal GT
Gestational DM

GI
>140
>200
<200

DM
>105
>165
>145

Diagnosis of DM
Sufficient classical symptoms plus unequivocal
elevation of FBS - 200 mg%
Elevation of FBS >140 mg%
[on more than one occasion]
Normal FBS but OGTT at 2 hr >200 mg%
[on more than one occasion]

Acute Pancreatitis
S/S: severe epigastric pain radiating to the back,

vomiting, fever, abdominal distension, paralytic ileus,

hypotension, shock
Associated with alcohol abuse or biliary tract stones

in 60-70% of cases
Non-specific Laboratory tests

Mild to moderate leukocytosis

Moderate post-prandial hyperglycemia

Mild hyper-bilirubinemia

++

Decreased serum Ca
Serum Amylase

Most commonly used

Average sensitivity: 85-90%

Average specificity: 45-50%

Urine Amylase

When serum amylase is normal or equivocally

elevated

Rises 24 hr after serum amylase

Amylase-creatinine clearance ratio: simultaneous

collection of serum & urine specimen

Other tests

Serum lipase

Serum trypsin
ERCP

CT Scan

Ultrasound

rainwater@mymelody.com || 1st semester, AY 2011-2012