Chapter 8 Renal Function Tests final.ppt

CHAPTER 8
Renal Function Testing and Non-protein
Nitrogen Substances

Objectives
Upon completion of this chapter the student will be able to:
 Define terminologies applied in the renal function tests
 Discuss the anatomy, physiology and pathophysiology
of the renal system
 Define the non protein nitrogenous (NPN) compounds
 Discuss about, NPN compounds mainly of Creatinine,
urea, and uric acid and their source, metabolism, and
clinical significance
3/4/2024
2 Compiled by-Mohammed Aliye

Objective, continued….
 Explain about Creatinine, urea, and uric acid tests
 principle of the test
 equipment and reagents
 type of specimen
 method procedure
 quality control
 source of error
 Interpretation
 limitation of the test
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Objectives cont…
 Convert BUN values into urea and vice versa,
using correct conversion factors
 Discuss renal clearance tests such as creatinine,
and others
 Calculate renal clearance tests result, and urea
creatinine ratio
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Outline of renal function tests
 Definitions of important terminologies
 Anatomy, physiology and pathophysiology of the renal
system
 Non- protein nitrogenous (NPN) compounds
 Urea and Blood urea Nitrogen (BUN)
 Creatinine
 Uric acid
 BUN/creatinine ratio
 Clearance tests
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Definitions
 Non protein nitrogenous (NPN) substances: are end
products of metabolism that contains nitrogen
 Azotemia: An excess of urea or other nitrogenous
compounds in the blood
 Anti diuretic hormone (ADH): is a posterior pituitary gland
hormone, important for reabsorption of water from the
kidneys.
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 Diabetic insipidus: A disorder associated with
secretion and metabolism of anti diuretic hormone
(ADH), manifested by excessive urine production.
 Renal clearance: The volume of plasma from which a
given substance is cleared completely by the kidneys
per unit of time
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Definitions cont…
 End stage of renal disease: a condition which renal
function is in adequate to supply life.
 The best treatment for such patients is either kidney
transplantation or dialysis treatment.
 Glomerulus's filtration rate: a measure of function of
nephrones, particularly creatinine and urea filtration rate
from glomerulus into bowmans capsule per millimeters
per minute
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Definitions, cont…
 Nephron: functional units of kidney
 Gout: Group of disorders of purine metabolism
 Renal failure: Acute or chronic decline in renal function
 Hyperuricemia is defined as an elevated serum uric acid
level
 Hyopuricuria: deficience of uric acid in the blood due to
deficiency of xanthineoxidase, the enzyme required for
covenrsion of hypoxantine to xantine and xanthin to uric
acid.
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Major Structures of Urinary System
 Kidney
 Ureters
 Bladder
 Urethra
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Review of the Urinary System
Kidney: Structure
 Bean shaped paired organs
 Outer layer = cortex; composed primarily of
glomeruli, PCT, DCT
 Inner layer = medulla; composed primarily of
the loop of Henle and collecting ducts
 Renal pelvis: collects urine into the ureters
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• Ureters: urine flows from renal pelvis into the ureters,
then into the bladder
• Bladder: urine stored here until voided
• Urethra: urine voided through urethra to outside of
body
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Kidney Functions
 Filtration of small molecules
 Reabsorption of essential substances
 Secretion into urine from blood stream
 Excretion
 Hormonal regulation: erythropoietin, ADH,
aldosterone
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Major Components of Kidney
 Nephron
 Arterioles:
 Afferent
 Efferent
 Glomerulus
 Bowman’s
capsule
 Tubules:
 PCT, Loop of
henle, DCT,
Collecting
tubules
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A. Nephron
 This is the functional unit of the kidney
 Each kidney contains approx 1 million nephrons
 Composed of three main units
 Arterioles: afferent and efferent
 Glomeruli
 Tubules: PCT, Loop of Henle, DCT, Collecting
Ducts (tubules)
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B. Arterioles
 Afferent arteriole: supplies blood to the
glomerulus
 Efferent arteriole: outgoing blood supply from
the glomerulus to peritubular capillaries or
vasa recta which surround the tubules
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C. Glomerulus
 Tuft of porous capillaries that is formed from the
afferent arteriole and drained by the efferent
arteriole
 Function
 Filtration based on molecule size and charge
 Water and small diameter/molecular weight
molecules rapidly pass through the filtration
barrier with little or no resistance
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D. Bowman’s Capsule
 Surrounds the glomerulus, opening into the
proximal convoluted tubule
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E. Tubules
1.Proximal Convoluted Tubule (PCT): reabsorb
essential substances (water)
2.Loop of Henle: he loop of Henle is a part of the
Nephron in the kidneys, which helps to reabsorb
water and salt from the kidney tubules. concentrate
urine
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4. Distal Convoluted Tubule (DCT): homeostatic
regulation
5. Collecting Tubules (Ducts): directs urine
flow into renal pelvis; responsive to the
hormones ADH and aldosterone
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Compiled by-Mohammed Aliye
20

Glomerular Filtration
 Non-selective filtration across the semi-permeable
membrane of the capillary tuft
 Occurs due to the high hydrostatic pressure created
by the afferent and efferent arterioles
 All substances with molecular weight <70,000 filtered
into urine
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Glomerular Filtration Rate (GFR)
 Defined as the volume of fluid that is filtered across the
glomerular capillary membrane per minute
 Approximately 120 ml of ultrafiltrate is formed per minute
 GFR depends on:
1) Net filtration pressure: blood and oncotic pressures
2) Permeability and area of the glomerular membrane:
changes with physiology and disease
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Tubular Reabsorption
1. Conservation of water and nutrients
a. Returns substances to plasma from Glomerular
filtrate
b. Passive transport mechanism:
1)Requires no energy expenditure by the body;
simple diffusion
2)Water, urea, chloride (as NaCl)
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c. Active transport mechanism:
1)Requires metabolic energy from transport cells
to carry substances against a gradient
 Active transport depends on the concentration of the
substance in the blood
 Glucose, amino acids, Na+, K+, Mg2+ , Ca2+ ,
HCO3-
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Tubular Secretion
1.Substances in the peritubular capillary blood are
secreted into the filtrate for excretion through urine
2. Elimination of waste products not filtered by the
glomerulus
a. Medications bound to proteins (proteins remain in
blood stream)
b. Organic waste: urea, uric acid, creatinine
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Renal Threshold
 Defined as the plasma concentration of a substance
that when exceeded, the kidney tubules will not
reabsorb any more into the bloodstream, resulting in
the substance being excreted into the urine
 Substances are reabsorbed into the bloodstream
dependent upon their blood concentration and the
body’s needs
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 When the plasma concentration of a
substance is higher than a certain ‘threshold
value’, reabsorption of the substance is no
longer possible
 The substance is then spilled into the urine
 Example: glucose renal threshold is ~160-180
mg/dl
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Renal pathophysiology
 Renal pathophysiology deals with the abnormal
physiology of the renal system
 Signs and symptoms of renal failure:
Nausea, vomiting, edema, pain, shock, Urine
volume change, urine composition change….
 Types of renal failure
- acute renal failure and Chronic renal failure
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Acute renal failure (ARF):
 most commonly occurs in hospital setting as a result
of ischemic or nephrotoxic insults.
 develops rapidly
 laboratory results show electrolyte, acid-base, and
fluid imbalances.
 Depending on where the damage has occurred,
classified as pre renal, renal, or post renal.
 When causes removed, recovery may occur with
days and weeks.
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Chronic renal failure (CRF):
 progressive loss of functioning nephrons.
 The rate that CRF progresses depends on the
number of episods or ARF.
 Minor causes include Diabetes, renal vascular
disease, glomerulornephrites.
 Currently diagnostic tools include in situ
hybridization, PCR techniques.
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To Differentiate ART from CRF
evaluate patient history, biopsy, imaging kidneys(small
shrinking kidney indicate CRF)
Signs and symptoms of renal failure
 Symptoms:-Nausea, Vomiting, lethargy
;Micturia(frequency,nocturia, retention, and disuria), urine
volume (Polyuria, oliguria, anuria); alteration of urine
composition (hematuria, proteinuria, bacteuria, leuckuria,
calculi); pain (an inconsistent symptoms); edema
(hypoalbunemia, salt and water retention)
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Causes, agent, and progress parameters of
acute renal failure
Cause Agent Test and progress
parameters
Prerenal
Hypovolemia
Decreased plasma volume
Decrease cardiac output
Renovascular obstruction
Interferance with renal
autoregulation
Trauma, burns, surgery
Nephrotic syndrom, sepsis;, shock
Congestive cardiac failure, pulmonary
embolism
Atherosclerosis, stenosis
ACE inhibitors, cyclosorin
Measurment of
elecrolytes,
acid base, urine
volumes,
NPN blood and
urine
concentration.
Renal
Glomerular and small vessels
disease
Interstitial nephritis
Tubular lesions
Aggressive glomerulonephrities
Infection, infiltration, drugs, toxins
Postischemic, nephrotoxine,
hypercalcemia
Post renal
Bladder outflow obstruction
Uretric obstruction
Prostatism, neurogenic bladder
Stones, blood clot, tumors,
radiotherapy,retroperitoneal fibrosis 3/4/2024

Renal diseases
 Glomerular disease
 Cystic renal disease
 Diabetes
 Renal calculi
 Toxic nephropathy
 Obstructive uropathy
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Non-Protein Nitrogen (NPN) Compounds
 These are compounds that contain nitrogen, but are
not proteins
 End products of metabolism
 The kidneys play an essential role in the excretion of
these metabolic waste products.
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Most clinically significant NPN compounds are:
1. Amino acids: from protein catabolism (breakdown)
2. Ammonia: from amino acid catabolism
3.Urea: from ammonia catabolism
4.Creatinine: from creatine breakdown in the muscle
5.Uric acid: from nucleic acid catabolism

NPN cont…
 Include >15 compounds
 Amino acids
 Ammonia
 Blood urea nitrogen (BUN)
 Creatinine
 Uric acid
Muscle breakdown product
Protein  amino acids  ammonia  urea
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NPN cont…
 Because the kidneys act to excrete these
compounds into urine, measurement of NPN
compounds in plasma is useful for assessment of
kidney function
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Urea and BUN
 NPN compound present in highest concentration in blood
and urine
 U= Urea
 Blood Urea Nitrogen = BUN
 Urea contains 2 nitrogen atoms: 28 g nitrogen/mole
of urea
 BUN x 2.14 = urea the origin of the conversion factor is:
 MW of urea = 60 g/mole
 AW of N = 14
 14x 2 = 28
 60/ 28 = 2.14
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Urea (BUN)
 Formation and excretion
 Synthesized in the liver: ammonia  urea
 Conversion of ammonia to urea is last liver function to
fail in end stage liver disease
 Plasma ammonia levels rise
Protein  amino acids  ammonia [LIVER]  urea
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Biochemistry of Urea
 Synthesized in the liver from CO2 and the ammonia, from
the deamination of amino acids.
 Major excretory product of protein metabolism.
 Readily filtered from the plasma by the glomerulus.
• 40% is reabsorbed by passive diffusion.
• Reabsorption depends on urine flow rate
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Urea
• <10% are excreted through the GI tract and skin.
• Plasma concentration depends on:
 Renal function
 Protein content of the diet
 The amount of protein catabolism
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Urea
A. Formation and Excretion
1. Synthesized in the liver
2.Most of the urea formed is excreted through the
kidneys into the urine
3. If liver function is intact then plasma ammonia
levels won’t rise.
4. Blood urea nitrogen (plasma urea) levels will rise
in renal function failure.
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Urea (BUN)
 Clinical Significance:
 Plasma levels are dependent upon
 Diet
 Liver function
 Kidney function
 State of hydration
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Urea cont…
• Azotemia - an elevated concentration of urea in the
blood.
• Uremia or Uremic syndrome- a very high plasma urea
concentration accompanied by renal failure
 Fatal if not treated
 Treatment
 dialysis
 transplantation.
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Conditions causing elevations of plasma urea are classified
according to cause into three main categories: Pre renal,
Renal, Post renal.
 Clinical Significance of BUN:
1.Serum/plasma urea levels will vary depending upon
a.Diet
b.Liver function
c.Kidney function
d.State of hydration
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2.Increased urea (BUN)
a.Increased protein intake  increased
synthesis
b.Decreased kidney function: decreased
excretion
c.Dehydration

Urea cont…
3. Decreased urea (BUN)
a. Decreased protein intake  decreased synthesis
b. Decreased liver function (severe): decreased
ammonia to urea conversion, leading to increased
ammonia levels
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Methods of Urea Measurement
 Enzymatic (indirect) method
 Chemical (direct) method
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1.Enzymatic methods (indirect method)
a. Based on the preliminary hydrolysis of urea with
urease (specific enzyme) to liberate ammonium ions,
followed by a secondary reaction that measures the
amount of ammonium ion spectrophotometrically
 Called ‘indirect’ methods because these methods
measure the amount of ammonia ‘liberated’ from the
urea molecule present in the sample
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49

Enzymatic urea methods
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Methods cont
 The amount of ammonium ion produced is directly
proportional to the amount of urea Glutamate
dehydrogenase
 Spectrophotometric measurement of NADH  NAD (ABS
at 340 nm).
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52
 The amount of NAD produced is directly
proportional to the amount of ammonium ion
which is directly proportional to the amount of
urea present
 This method may use a manual
spectrophotometer, semi-automated
spectrophotometer or automated Clinical
Chemistry analyser to measure BUN.

Methods cont…
 Disadvantage: endogenous ammonia will interfere
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Methods cont…
2. Chemical methods
 Called ‘direct’ methods because urea in sample reacts directly
with reagent causing a color change that is
spectrophotometrically measured
 Color reagent: diacetyl-monoxime
 Advantage: endogenous ammonia does not interfere
 Based on the condensation of urea with diacetyl monoxine;
then spectrophoptometric measurement of the colored product
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BUN to Urea Conversion
 Nitrogen gram molecular weight:14 g/mole
 Urea contains 2 nitrogens:28 g N/mole of urea
 Molecular weight of urea: 60 g/mole
 60/ 28 = 2.14
 BUN x 2.14 = urea
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Specimen collection/handling
 Urine
 Timed collection preferred
 Must be diluted prior to measurement1:10, 1:20
 Stability: up to 1 week stored in refrig when pH<5
 Some bacteria are able to hydrolyze urea to
ammonia resulting in falsely decreased urine urea
levels
 As ammonia increases in the urine, the pH becomes
more alkaline
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Urea Specimens
 Serum or heparinized plasma
 Stability: up to 24 hours at room temperature; 1 week at
2-4oCSpecimen Collection and Handling Requirement for
BUN
 Serum or heparinized plasma, non-hemolyzed; fasting not
required
a. Fluoride and citrate cannot be used because they
inhibit enzyme activity
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Quality Control
 A normal & abnormal quality control sample should
be analyzed along with patient samples, using
Westgard or other quality control rules for
acceptance or rejection of the analytical run.
 Assayed known samples
 Commercially manufactured
 Validate patient results
 Detects analytical errors.
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Limitations: Urea Methods
 Sources of error
 Specimen:
 Hemolyzed or Lipemia
 Fluoride and citrate
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Urea references
 BUN Reference Range:
-adults (Serum/plasma)……………….. 6-20 mg/dl
-New borne upto one week( Serum/plasma)…3- 25mg/dl
-Adult over 60 (Serum/plasma) ……………..8-23mg/dl
 Urine, 12-20 g/24hrs
Convert 22 mg/dL BUN to urea mg/dL
BUN 22 x 2.14 = Urea 47 mg/dL 3/4/2024

Documentation of Test Results
 Record patient results in result logbook
 Record QC results in QC logbook
 Retain records for recommended time
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Creatinine
 Formation and Excretion
 Spontaneously derived from creatine in muscle
 High energy ATP storage and use in muscle
 Produced at a constant rate day to day
 Excreted into urine through glomerular filtration; not
significantly reabsorbed or secreted by tubules
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Creatinine
Clinical Significance of Creatinine
1.Endogenous substance
2.Amount produced is relatively constant and proportional
to muscle mass
3.Amount excreted into urine is constant from day to day
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66
4. Filtered almost entirely by the glomerulus;
not significantly secreted or reabsorbed by
tubules
5. Show little or no response to dietary
changes

Creatinine
 Increased serum creatinine
 Renal disease = impaired renal function
 50-60% renal function lost before serum
creatinine increased
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 Increased serum creatinine
a. Impaired renal function: increased
creatinine levels not apparent until 50-66% of
renal function lost
b. Decreased glomerular filtration rate results
in less creatinine being filtered by the
glomerulus causing increased serum
creatinine

Methods of Creatinine Measurement
 Creatinine + alkaline picrate  Janovski complex
(yellow) (red-orange color)
1. Chemical method: Jaffe Reaction
a. This reaction lacks specificity:
1)Falsely increased results with high levels of:
protein, ascorbic acid, ketones, glucose,
pyruvate and uric acid
2)Falsely decreased results: bilirubin
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Creatinine
b. Several modifications have been used to increase the
specificity of this reaction:
1) Prepare a protein-free filtrate (PFF):
a. React with tungstic acid to precipitate out protein
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71
2) Kinetic Jaffe reaction: detection of the rate of
color formation is timed such that interfering
substances do not interfere. This is common
with most automated methods of analysis.
c. Most frequently used methods are based on
the Jaffe reaction, even though bias present
due to interference: inexpensive, rapid and
easy method to perform

Creatinine
2. Coupled enzymatic method
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Creatinine Specimen Collection and
Handling
 Urine
 Time collection preferred; random acceptable
 Stability: up to 4 days in refrigeration
 Longer when frozen
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Creatinine
 Serum or heparinized plasma
 Avoid hemolysis
 Avoid lipemia
 Stability: one week at refrigeration temps
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Quality Control
 A normal & abnormal quality control sample should
be analyzed along with patient samples, using
Westgard or other quality control rules for
acceptance or rejection of the analytical run.
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Creatinine Method Limitations
 Sources of Error:
 Falsely increased results with high levels of: protein,
ascorbic acid, ketones, glucose, pyruvate and uric
acid
 Falsely decreased results: bilirubin
 Specimen hemolysis or lipemia
 Note the modifications mentioned to limit sources of
error:
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Creatinine references
Reference Range
 Serum Adult male:
Adult female:
Child:
 Urine Male: g/24hr
Female: g/24hr
 Amniotic fluid: mg/dl
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Uric Acid
A. Formation and Excretion
1. End product of purine (adenine and guanine) metabolism
by the liver
2. Purines are precursors of the nucleic acids ATP and GTP
(adenosine diphosphate and guanosine triphosphate)
3. Readily filtered by the glomerulus, but then undergoes a
complex cycle of reabsorption and secretion by the tubules
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Uric Acid
Clinical Significance of Uric Acid
1.Increased uric acid (hyperuricemia)
a. Gout: at plasma pH uric acid is readily insoluble
and at concentrations >6.4 mg/dl the plasma is
saturated resulting in crystal deposition in tissues and
joints
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b. Increased catabolism of nucleic acids
1) Patients on chemotherapy for proliferative
disease such as leukemia, lymphoma, multiple
myeloma, polycythemia
2) Must monitor uric acid levels to avoid
nephrotoxicity

Uric Acid
3) Allopurinol treatment is used to interrupt the
uric acid synthesis pathway in these patients,
avoiding nephrotoxicity
c. Renal disease: filtration and secretion are impaired
2. Decreased uric acid (hypouricemia)
a. Severe liver disease
b. Defective tubular reabsorption
c.Over treatment with allopurinol
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Methods of Uric Acid Measurement
1.Caraway method
a. Phosphotungstic acid (PTA) reduction by uric
acid
b. Historical, lacks specificity (uric acid is a
reducing substance, thus other reducing
substances will also react in this method)
2. Uricase method: increased specificity
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Specimen Collection and Handling
Requirement for Uric Acid
1.Serum or heparinized plasma;
a. Avoid hemolysis and gross lipemia
b.aspirin may cause increased results
c. Stability: 3-5 days at 2-4oC
2.Urine
a.Timed urine collection preferred
b.Sample should be refrigerated to inhibit bacterial
growth
3.Stability: 3-5 days at 2-4C
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Quality Control
 A normal & abnormal quality control sample
should be analyzed along with patient samples
 Detects analytical errors
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Reference Range Uric acid
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BUN/Creatinine Ratio
 Used by clinicians to differentiate causes of azotemia:
 Pre-renal
 Post-renal
 Azotemia: condition of increased NPN in
blood
 Most often due to increased BUN and creatinine
 The major NPN used to evaluate kidney function
 Also uric acid
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 Calculated: serum BUN (mg/dl)
serum creatinine (mg/dl)
 Normal ratio: 10-20 with majority around
12-16
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 Differentiation of azotemia
 Increased ratio with
increased BUN,
normal creatinine
Tend to be caused by pre-
renal conditions:
Congestive Heart Failure
Dehydration
Increased protein metabolism
Increased protein catabolism
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BUN/Creatinine Ratio Cont…
dysproportionate
increased BUN,
slightly increased
creatinine
Tend to be caused by post-
renal conditions that obstruct
urine flow:
Stone
Tumor
Sever infection 3/4/2024

BUN / Creatinine
 Post-renal conditions tend to have an increased
ratio along with slightly increased creatinine level
due to obstruction of urine flow or pre-renal
azotemia superimposed on renal disease
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increased BUN,
increased creatinine Tend to be caused by - renal
conditions that decrease
kidney function:
Acute renal failure
Chronic renal failure
Glomerulonephritis
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 Decreased ratio
with decreased
BUN
Tend to be caused by
conditions of decreased urea
production:
Low protein diet
Liver disease
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Clearance Test: Monitor GFR
 Renal clearance expresses volume of blood cleared
of a substance per unit of time
 The clearance of a substance is the volume of plasma
from which that substance is removed per unit time
Example: mL of substance per minute
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Clearance Test: Monitor GFR
 Substance used to monitor GFR must meet the
following criteria:
 Filtered exclusively by glomerulus
 Not reabsorbed by kidney tubules
 Not secreted by kidney tubules
 Most often used = creatinine clearance
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 The GFR is the volume of plasma filtered (V) by
the glomerulus per unit of time (t)
 Creatinine clearance, a measure of the amount of
Creatinine eliminated from the blood by the
kidneys, and GFR are used to gauge renal
function
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Creatinine Clearance (CrCl)
 Why is creatinine clearance most often used to
monitor GFR?
 Creatinine freely filtered by glomerulus
 Creatinine not ‘rehandled’ by tubules
 Creatinine is an endogenous substance
 Amount of creatinine produced per day is constant
 Amount of creatinine produced is proportional to
muscle mass
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Clearance Test
 Patient preparation
 Patient should be well hydrated
 Avoid coffee and tea (caffeine) on day of test
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Creatinine Clearance (CrCL)
 Specimen collection/handling
 Timed urine collection: 24 hour preferred
 Measure total volume of urine collected
 Measure urine creatinine (mg/dl)
 Serum/heparinised plasma
 Collect blood specimen sometime during the urine
collection period
 Measure serum/plasma creatinine (mg/dl)
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CrCl
 Standard clearance formula:
UV U = urine creatinine (mg/dl)
P V = total volume of urine collected: ml/min
P = plasma creatinine (mg/dl)
 Clearance corrected for body surface area:
UV x 1.73 A = body surface area (BSA)
P A 1.73 = average BSA
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CrCl vs Urine Creatinine
Consider the following data:
Serum creatinine: 1.8 mg/dl
Urine creatinine: 63 mg/dl
Total urine volume: 1680 ml/24hr = 1680 ml/1440
minutes
Patient height: 178 cm
Patient weight: 82 Kg
1. Calculate the CrCl
2. Calculate the corrected CrCl for body surface area
3/4/2024

Total urine volume: 1680 ml/24hr = 1680 ml/1440
minutes
1. Calculate the CrCl = UV/P
63 mg/dl x 1680 ml = 40.8 = 41 ml
1.8 mg/dl 1440 min min
3/4/2024

Total urine volume: 1680 ml/24hr = 1680 ml/1440 minutes
Patient height: 178 cm
Patient weight: 82 Kg
Surface area = 2.00 m2
2. Calculate the corrected CrCl for body surface area
41 ml x 1.73 = 41 x 0.87 = 35.7 = 36 ml
min 2.00 min
Corrected CrCl:
CrCl x 1.73 = 41 ml x 1.73 = 41 x 0.87 = 35.7 =
36 ml
BSA min 2.00 min 3/4/2024

ESTIMATED GLOMERULAR FILTRATION
RATE (eGFR)
 Glomerular Filtration Rate (GFR) is the amount of
blood filtered every minute by tiny filters in the kidneys
called glomeruli.
 It measures how well your kidneys are working
 The main job of our kidneys is to remove waste and
excess water from the blood
 This excess water and waste become urine.
 Kidneys process about 50 gallons (180 liters) of blood
every day to produce about 1.5 liters of urine
3/4/2024
105

Estimated GFR (EGFR)
 National Kidney Foundation recommends a
EGFR be calculated each time a serum creatinine
is reported
 Want to detect chronic renal disease earlier
 Predicts GFR based on patient age, sex, body
size, race, serum creatinine
3/4/2024

 When the filtration rate decreases that means the
kidneys are not working well and may mean there is
kidney damage
 It is hard to directly measure one’s GFR. Instead,
developed a formula to estimate the value indirectly.
 It’s called it the eGFR, or estimated Glomerular
Filtration Rate.
 It takes into account your age, gender, ethnicity/race,
and your creatinine levels 3/4/2024
107

 eGFR often helps in the early detection of kidney
dysfunction, which is important to prevent further
kidney damage
 eGFR a better measure of kidney function than
creatinine, or other kidney-associated markers such
as BUN (blood urea nitrogen)
 Because it is more sensitive.
3/4/2024
108

Estimated GFR (EGFR)
EGFR (ml/min) =
(140 - age) x (Weight in kg) x (0.7 if female)
72 x Serum creatinine in mg/dl
3/4/2024

 High eGFR
A high level is usually not a cause for concern. high
eGFR is normally found in pregnancy
 Low eGFR
 Reduced eGFR indicates impaired kidney function.
 It can point to a largely reversible acute kidney
injury or to a chronic kidney disease that is often
irreversible and persistent.
3/4/2024
110

Chronic kidney disease measured by
eGFR has the following stages:
 Stage 1: normal, eGFR: > 90 ml/minute
 Stage 2: mild CKD, eGFR: 60 – 89 ml/minute
 Stage 3: moderate CKD, eGFR: 30 – 59 ml/minute
(30 – 60% of kidney function intact)
 Stage 4: severe CKD, eGFR: 15 – 29 ml/minute (15 –
30% of kidney function intact)
 Stage 5: kidney failure, eGFR < 15 ml/minute (less
than 15% of kidney function intact)
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111

3/4/2024
112

Creatinine Clearance
 Reference Range
Adult male: 97-137 ml/min
Adult female: 88-128 ml/min
EGFR: >59 ml/min
3/4/2024

Creatinine Clearance
 Clinical Significance
 Used to monitor GFR
 As renal function fails, CrCl decreases
 Dialysis indicated when CrCl critically low
(GFR ~ 10-20 mL/min)
 Correlates with Increased BUN/ Creatinine ratio with
increased BUN, increased plasma creatinine and
decreased urine creatinine
3/4/2024

Quality Control
 A normal and abnormal quality control sample should be
analyzed along with patient samples, using Westgard or
other quality control rules for acceptance or rejection of
the analytical run.
3/4/2024

3/4/2024

Summary
 Renal function tests: metabolic pathways,
methods of analysis, calculations, interpretations
and correlation of results
 BUN/ urea
 Creatinine
 Uric Acid
 Creatinine Clearance
3/4/2024

Review Questions
 What is the principles of the enzymatic methods
of analysis of urea, uric acid and creatinine?
 What is the principle of the classic creatinine
method?
 What are sources of error in the urea method?
 Why is BUN/ creatinine ratio useful?
 What is the formula for calculating creatinine
clearance? 3/4/2024

Reference
1. Burtis, Carl A., and Ashwood, Edward R. Tietz:
Fundamentals of Clinical Chemistry. WB Saunders,
Co., Philadelphia, 2001.
2. Arneson, W and J Brickell: Clinical Chemistry: A
Laboratory Perspective 1st ed. FA Davis, Co.,
Philadelphia, 2007
3. Burtis, Carl A., and Ashwood, Edward R. Tietz:
textbook of Clinical Chemistry. WB Saunders, Co.,
Philadelphia, 1999.
3/4/2024

The next Chapter
Chapter 9
Lipids
3/4/2024

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