Download Creatinine

Kidney function test
Functions of the kidney
 Regulation e.g. homeostasis ,water,
acid/base
 Excretion e.g.uric acid, urea, creatinine
 Endocrine e.g. renin, erythropoietin, 1,25
dihydroxycholecalciferol- conversion only in
kidney!
When should you assess renal
function?
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Risk factors for kidney disease:
– Older age
– Family history of Chronic Kidney disease (CKD)
– Decreased renal mass
– Low birth weight
– US racial or ethic minority
– Low income
– Lower education level
– Diabetes Mellitus (DM)
– Hypertension (HTN)
– Autoimmune disease
– Systemic infections
– Urinary tract infections (UTI)
– Nephrolithiasis
– Obstruction to the lower urinary tract
– Drug toxicity
Uric acid
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Uric acid is a chemical created when the body
breaks down substances called purines.
Purines are found in some foods and drinks, such
as liver, anchovies, mackerel, dried beans and peas,
beer, and wine.
Purines are also a part of normal body substances,
such as DNA.
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In humans, approximately 75% of uric acid excreted
is lost in the urine; most of the reminder is secreted
into the GIT
If your body produces too much uric acid or doesn't
remove enough if it, you can get sick.
High levels of uric acid in the body is called
hyperuricemia
Normal values fall between 3.0 and 7.0 mg/dL.
Note: Normal values may vary slightly from
laboratory to laboratory.
When is it ordered?
when a doctor suspects high levels of uric acid :
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Gout
monitoring test when a patient has undergone chemotherapy or
radiation
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if a patient appears to have failing kidneys
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Greater-than-normal levels of uric acid (hyperuricemia)
may be due to:
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Alcoholism
Diabetes
Gout
Hypoparathyroidism
Lead poisoning
Leukemia
Nephrolithiasis
Polycythemia vera
Renal failure
Toxemia of pregnancy
Purine-rich diet
Excessive exercise
Chemotherapy-related side effects
Lower-than-normal levels of uric acid may be due
to:
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Fanconi syndrome
Wilson's disease
Syndrome of inappropriate antidiuretic hormone (SIADH)
secretion
Multiple Sclerosis
Low purine die
Gout
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Gout is a kind of arthritis that occurs when uric acid builds up in
the joints.
In Gout increased serum levels of uric acid lead to formation of
monosodium urate crystals around the joints.
Acute gout is a painful condition that typically affects one joint.
Chronic gout is repeated episodes of pain and inflammation,
which may involve more than one joint.
The exact cause is unknown. Gout may run in families. It is more
common in males, postmenopausal women, and people who
drink alcohol
Symptoms of acute gouty attacks:
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Symptoms develop suddenly and usually involve
only one or a few joints. The big toe, knee, or ankle
joints are most often affected .
The pain frequently starts during the night and is
often described as throbbing, crushing, or
excruciating .
The joint appears warm and red. It is usually very
tender.
There may be a fever .
The attack may go away in several days, but may
return from time to time. Additional attacks usually
last longer .
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After a first gouty attack, people will have no symptoms. Some
people will go months or even years between gouty attacks.
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Some people may develop chronic gouty arthritis, but others may
have no further attacks. Those with chronic arthritis develop joint
deformities and loss of motion in the joints. They will have joint
pain and other symptoms most of the time.
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Tophi are lumps below the skin around joints or in other places.
They may drain chalky material. Tophi usually develop only after
a patient has had the disease for many years.
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After one gouty attack, more than half of people will have another
attack.
A tophus on the elbow of a middle aged man with
chronic gout .
Tests that may be done include:
Synovial fluid analysis
Gold standard to confirm gout,
Urate crystals identified by:
- Needle and rod shapes
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Uric acid - blood
Joint x-rays) may be normal)
X-ray of gouty uric acid deposit in the big toe (left )
Possible Complications
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Chronic gouty arthritis
Kidney stones
Deposits in the kidneys, leading to chronic kidney
failure
Treatment
Treatments for a sudden attack or flare-up of gout :
 Your doctor will recommend that you take
nonsteroidal anti-inflammatory drugs (NSAIDs) such
as ibuprofen, naproxen, or indomethacin as soon as
your symptoms begin
 Your health care provider may occasionally
prescribe strong painkillers such as codeine
 Daily use of allopurinol decrease uric acid levels in
your blood
Some diet and lifestyle changes may help
prevent gouty attacks :
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Avoid alcohol, sardines, oils, organ meat (liver,
kidney, and sweetbreads(
Limit how much meat you eat at each meal.
Avoid fatty foods such as salad dressings, ice
cream, and fried foods
Eat enough carbohydrates
If you are losing weight, lose it slowly. Quick weight
loss may cause uric acid kidney stones to form.
Specimen
Serum or plasma may be used; slight but insignificant
positive bias (0.2 mg/dL) has been noted in plasma
specimens as compared with serum.
Stability in serum / plasma:
6 months at -20°C
7 days at 4-8°C
3 days at 20-25°C
Enzymatic Colorimetric
1-Uric acid + H2O + O2
Uricase
Allantion + CO2 + H2O2
2-TBHBA + 4- Aminoantipyrine + 2H2O2
Quinoneimine + 3 H2O
POD
-Uric acid is oxidized to allantoin by uricase.
-The generated hydrogen peroxide reacts with 4aminophenazone/ESPT to quinoneimine.
Note:
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Uric acid may also form kidney stones
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Although uric acid can act as an antioxidant, excess
serum accumulation is often associated with
cardiovascular disease.
urea
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Urea is a relatively nontoxic nitrogen containing substance made by
the liver to dispose of ammonia resulting from protein metabolism.
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Its elimination in the urine represents the major route for nitrogen
excretion.
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The reference interval for serum urea of healthy adults is 5-39 mg/dl
(slightly higher in males than females)
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BUN = (blood urea nitrogen)
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The real urea concentration is BUN x 2.14
Increased BUN = Azotemia
Causes:
– Increased protein catabolism:
 Increased dietary protein
 Severe tress: MI, fever, etc
 Rhabdomyolysis
 Upper GI bleeding
– Impaired renal function
 Pre renal azotemia: renal hypoperfusion
 Renal azotemia: acute tubular necrosis
 Post renal azotemia: obstruction of urinary flow
Decreased BUN
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Decreased dietary protein
Increased protein synthesis ( Pregnant women , children )
severe liver disease
SIADH
Overhydration (IV fluids)
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The key to identifying the azotemia as
prerenal is the increase of plasma urea
without parallel increase of plasma
creatinine.
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With obstruction, both plasma urea and creatinine
increase, but there is greater rise of urea than of
creatinine because the obstruction of urine flow 
backpressure on the tubule and back diffusion of urea
into blood from the tubule.
BUN / Creatinine Ratio
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Pre-renal
BUN is more susceptible
to non-renal factors
Post-renal
Both BUN and Creat. are
elevated
Increased BUN
Normal Creat
Increased BUN
Increased Creat
Specimen
-Serum and heparinized plasma can be used for the
urease/GLDH methods.
-Fluoride will inhibit the urease reaction; therefore methods
employing urease cannot use serum preserved with
fluoride.
-Ammonium heparin also cannot be used as an anticoagulant
for urease methods.
-Stability in serum or plasma:
7 days at 4–8°C
1 year at -20°C
-Because of urea’s susceptibility to bacterial degradation,
serum and urine samples should be kept at 4° to 8° C until
analysis.
Urease/GLDH Method
-The method is optimized for 2-point kinetic
measurement.
-Decrease in absorbance at 340 nm is proportional to
concentration of urea.
creatinine
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Creatine is synthesized in the kidneys and
liver
It is then transported in blood to other organs
such as muscle and brain, where it is
phosphorylated to phosphocreatine, a highenergy compound.
Interconversion of phosphocreatine and
creatine is a particular feature of metabolic
processes of muscle contraction
Creatinine
-Creatinine is a non-protein nitrogen waste product formed in
muscle.
Creatine Phosphate – phosphoric acid = Creatinine
Creatine – water = Creatinine
-Creatine is synthesized in liver from some a.a (glysine,
methionine, arginine).
-Filtered by kidney and excreted in the urine.
-Creatinine filters easily into the glomerular filtrate and is not
reabsorbed by the tubule.
-The plasma levels of creatinine are related to the muscle mass.
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1 to 2% of muscle creatine spontaneously
converts to creatinine daily and released into
body fluids at a constant rate.
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Endogenous creatinine produced is proportional
to muscle mass, it is a function of total muscle
mass the production varies with age and sex
creatinine
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The breakdown product of creatine phosphate
released from skeletal muscle at a steady rate.
It is filtered by the glomerulus.
It is generally a more sensitive and specific test
for renal function than the BUN.
Normal range is 0.6-1.3 mg/dL– *non pregnant
state-*
Increased serum creatinine:
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– Impaired renal function
– Very high protein diet
– Vary large muscle mass: body builders, giants, acromegaly
patients
– Rhabdomyolysis/crush injury
– Athletes taking oral creatine
– Drugs:
• Probenecid
• Cimetidine
• Triamterene
• Trimethoprim
• Amiloride
Specimen
-One can analyze serum, plasma, or diluted urine.
-The common anticoagulants (fluoride and heparin) do not
cause interference, though heparin, which can be
formulated as the ammonium salt, must be avoided in
enzymatic methods that measure ammonia production.
-Storage
7 days at 4-25oC
At least 3 months at -20oC
Specimen
-Urine should be diluted 1:100
-Bacterial contamination has been found to falsely lower
creatinine values measured using the Jaffé reaction.
-The mechanism of this interference appears to be bacterial
production of a substance that retards the rate of the Jaffé
reaction.
Enzymatic Method
Creatinine aminohydrolase
Creatinine + H2O
Creatine +ATP
Creatine
Creatine Kinase
Creatine-P + ADP
Pyruvate Kinase
ADP + Phosphoenolpyruvate
Pyruvate + NADH
Lactate dehydrogenase
ATP + Pyruvate
Lactate + NAD+
-The difference in absorbance at fixed times during conversion is
proportional to the concentration of creatinine in the sample.
Principle of of Clearance
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Some substances when filtered enter the tubules
are not reabsorbed and so 100% excreted= GFR
(inulin= gold standard for GFR, creatinine (but this
one partially reabsorbed, particularly in uremia, then
clearance <GFR
Some substances are filtered, enter tubules, and
more of the substance is secreted enters the tubules
by excretion. Clearance>GFR
Some substances are filtered, enter tubules, but are
completely reabsorbed, so they did not reach the
final urine (e.g. cystatin C)
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Clearance is defined as the (hypothetical)
quantity of blood or plasma completely
cleared of a substance per unit of time.
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The most frequently used clearance test is
based on the measurement of creatinine.
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The 'clearance' of creatinine from plasma is
directly related to the GFR if:
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The urine volume is collected accurately
There are no ketones or heavy proteinuria present to
interfere with the creatinine determination.
It should be noted that the GFR decline with
age (to a greater extent in males than in
females) and this must be taken into account
when interpreting results.
Creatinine clearance in adults is
normally about of 120 ml/min
Plasma creatinine
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Plasma creatinine concentration is inversely related to the GFR
But GFR can decrease by 50% before plasma creatinine
concentration rises beyond the normal range this means that a
normal plasma creatinine does not necessarily imply normal
renal function,
A Raised creatinine usually indicates impaired renal function
Changes in plasma creatinine concentration can occur,
independently of renal function, due to changes in muscle
mass.
Decrease can occur as a result of starvation and in wasting
diseases, immediately after surgery.