CREATININE

Creatinine is a break-down product of creatine phosphate in muscle, and is

usually produced at a fairly constant rate by the body (depending on muscle
mass).

PHYSIOLOGY:

 Creatinine is mainly filtered by the kidney, though a small amount is

actively secreted.
 There is little-to-no tubular reabsorption of creatinine.
 If the filteration of the kidney is deficient, blood levels rise. As a result,
creatinine levels in blood and urine may be used to calculate the
creatinine clearance(ClCr), which reflects the glomerular filtration rate
(GFR).
 The GFR is clinically important because it is a measurement of renal
function. However, in cases of severe renal dysfunction, the creatinine
clearance rate will be "overestimated" because the active secretion of
creatinine will account for a larger fraction of the total creatinine
cleared.
 Ketoacids, cimetidine and trimethoprim reduce creatinine tubular
secretion and therefore increase the accuracy of the GFR estimate,
particularly in severe renal dysfunction. (In the absence of secretion,
creatinine behaves like inulin.)
 A more complete estimation of renal function can be made when
interpreting the blood (plasma) concentration of creatinine along with
that of urea.
 Urea concentration is given as blood urea nitrogen, in mg/dL. BUN-to-
creatinine ratio; ratio of urea to creatinine can indicate other problems
besides those intrinsic to the kidney for example, a urea level raised
out of proportion to the creatinine may indicate a pre-renal problem
such as dehydration.
 Men tend to have higher levels of creatinine because they have more
skeletal muscle than women.
 Vegetarians tend to have lower creatinine levels, because vegetables
contain no creatinine

DIAGNOSTIC USE:

 Measuring serum creatinine is a simple test and it is the most

commonly used indicator of renal function.
 A rise in blood creatinine levels is observed only with marked damage
to functioning nephrons. Therefore, this test is not suitable for
detecting early stage kidney disease.
 A better estimation of kidney function is given by the creatinine
clearance test.
CREATININE TESTS
Three types of tests on creatinine can be done:

1. BLOOD CREATININE LEVEL:

o The blood creatinine level shows how well kidneys are working.

o A high creatinine level may mean kidneys are not working properly.
The amount of creatinine in the blood depends partly on the amount of
muscle tissue; men generally have higher creatinine levels than
women.

2. CREATININE CLEARANCE TEST:

A creatinine clearance test measures how well creatinine is removed from

blood by kidneys.

o A creatinine clearance test gives better information than a blood

creatinine test on how well kidneys are working.

o A creatinine clearance test is done on both a blood sample and on a

sample of urine collected over 24 hours (24-hour urine sample).

3. BLOOD UREA NITROGEN-TO-CREATININE RATIO

o The levels of blood creatinine and blood urea nitrogen (BUN) can be
used to find the BUN-to-creatinine ratio.

o A BUN-to-creatinine ratio can help for problems, such as dehydration,

that may cause abnormal BUN and creatinine levels.

Creatinine clearance is calculated from the formula:

Urine Creatinine concentration x Urine volume (ml)

CrCl (ml/min) = ___________________________________________________

Serum Creatinine concentration x Period of

collection (min)
SIGNIFICANCE OF CREATININE CLEARANCE TEST

A blood creatinine level or a creatinine clearance test is done to:

• See if kidneys are working normally.

• See if kidney disease is changing.

• See how well the kidneys work in people who take medicines that can
cause kidney damage.

• See if severe dehydration is present. Dehydration generally causes

BUN levels to rise more than creatinine levels. This causes a high BUN-to-
creatinine ratio. Kidney disease or blockage of the flow of urine from your
kidney causes both BUN and creatinine levels to rise.

HOW TO PREPARE:

o Do not do any strenuous exercise for 2 days (48 hours) before having
creatinine tests.

o Do not eat more than 8 oz (227 g) of meat, especially beef, or other

protein for 24 hours before the blood creatinine test and during the
creatinine clearance urine test.

o It is important to drink enough fluids during the 24-hour urine

collection but do not drink coffee and tea. These are diuretics that
cause your body to pass more urine.

o Stop taking drugs that may affect the test. Such drugs include:

• Aminoglycosides (for example, gentamicin)

• Bactrim
• Cimetidine
• Heavy metal chemotherapy drugs (for example, Cisplatin)
• Nephrotoxic drugs such as cephalosporins (for example, cefoxitin)
• Vitamin C
• Methyldopa
• Trimethoprim
• Phenytoin

RESULTS
 o Creatinine and creatinine clearance tests measure creatinine levels in
blood and urine to give information about how well kidneys are
working.

o The creatinine clearance value is found from the amounts of creatinine

in the urine and blood and from the amount of urine passed in 24
hours.

o This value is the amount of blood cleared of creatinine per minute,

based on body size.

REFERANCE RANGE
Blood Creatinine: Men 0.6–1.2 (mg/dL) or 53-106 (mcmol/L)
Women 0.5–1.1 mg/dL or 44–97(mcmol/L)
Teen 0.5–1.0 mg/dL
Child 0.3–0.7 mg/dL
Newborn 0.3–1.2mg/dL
Conversion Fromula:
Serum: µmol/L x 0.011 = mg/dl
Urine: µmol/24 hours = mg/24 hours

Creatinine Clearance: Men 90–140 milliliters per minute (mL/min) or

1.78–2.32 milliliters per
second (mL/sec)
Women 80–125 mL/min or 1.45-1.78 mL/sec

Creatinine clearance values normally go up as you get older (normal values

go down by 6.5 mL/min for every 10 years past the age of 20).

BUN to Creatinine Ratio:

Over 12 months of age: 10:1 - 20:1

Infants(less than 12 months of age): Upto 30:1

o While a baseline serum creatinine of 2.0 mg/dL (150 μmol/l) may

indicate normal kidney function in a male body builder, a serum
 creatinine of 0.7 mg/dL (60 μmol/l) can indicate significant renal
disease in a frail old woman.

o More important than absolute creatinine level is the trend of serum

creatinine levels over time.
o Creatinine levels may increase when ACE inhibitors (ACEI) or
angiotensin-II receptor blockers (ARBs) are used in the treatment of
chronic heart failure (CHF).

HIGH VALUES

HIGH CREATININE BLOOD LEVELS:

High creatinine blood levels can mean serious kidney damage or disease is
present. Kidney damage can be caused by a life-threatening infection, shock,
cancer, or low blood flow to the kidneys.

Other conditions that can cause high blood creatinine levels include

• Blockage of the urinary tract (such as by a kidney stone),

• Heart Failure,

• Dehydration, excessive blood loss that causes shock,

• Gout,

• Muscle conditions (such as rhabdomyolysis, gigantism, acromegaly,

myasthenia gravis, muscular dystrophy, and polymyositis).

Usually a high blood creatinine level means that the creatinine clearance value
is lower than normal.

HIGH CREATININE CLEARANCE:

• High creatinine clearance values can be caused by strenuous exercise,

• Muscle injury (especially crushing injuries),

• Burns
 • Carbon monoxide poisoning,

• Hypothyroidism, and

• Pregnancy.

HIGH BUN-TO-CREATININE RATIO:

o High BUN-to-creatinine ratios occur with sudden (acute) kidney failure,

which may be caused by shock or severe dehydration.

o A blockage in the urinary tract (such as a kidney stone) can cause a

high BUN-to-creatinine ratio.

o A very high BUN-to-creatinine ratio may be caused by bleeding in the

digestive tract or respiratory tract.

LOW VALUES

LOW BLOOD CREATININE LEVELS:

o Low blood creatinine levels can mean lower muscle mass caused by a
disease, such as muscular dystrophy, or by aging.

o Low levels can also mean some types of severe liver disease or a diet
very low in protein.

o Pregnancy can also cause low blood creatinine levels.

LOW CREATININE CLEARANCE:

o Low creatinine clearance levels can mean serious kidney damage is

present.

o Kidney damage can be from conditions such as a life-threatening

infection, shock, cancer, low blood flow to the kidneys, or urinary tract
blockage.

o heart failure,

o dehydration,
 o liver disease (cirrhosis),

LOW BUN-TO-CREATININE RATIO

o A low BUN-to-creatinine ratio may be associated with a diet low in

protein,

o a severe muscle injury called rhabdomyolysis,

o pregnancy,

o cirrhosis,

o Syndrome of inappropriate antidiuretic hormone secretion (SIADH).

o SIADH sometimes occurs with lung disease, cancer, diseases of the

central nervous system, and the use of certain medications.

SERUM CREATININE ESTIMATION

PRINCIPLE:

Kinetic Calorimetric assay:

Alkaline
Creatinine + Picric acid Creatinine - Picric acid complex
Solution

In alkaline solution, creatinine forms a yellow-orange complex with picrate. The color
intensity is directly proportional to the creatinine concentration and can be measured
photo metrically.

REAGENTS:

R1:
Picric acid

R2:
Sodium hydroxide
Dilute 1 volume of R1 with 1 volume of R2 . Label it as Working Solution. It is stable for
10 days at + 2 0C – 8 0C or 1 day at + 20 0C – 25 0C
STANDARD:
Creatinine

SPECIMEN:

Collect serum using standard sampling tubes.

TESTING PROCEDURES:

ASSAY CONDITIONS:
 Wavelength: 492nm(480-520nm)
 Temperature: +370C
 Cuvette: 1cm light path
 Zero adjustment: air or distilled water

B S U
Standard - 100 µl -
Sample - - 100 µl
Reagent Distilled Water 1.0 ml 1.0 ml

Mix, pour immediately into the cuvettes. After exactly 20 seconds, take readings of
sample and standard (T1 and S1 respectively).Exactly 80 seconds after the first reading,
take another reading of sample and standard (T2 and S2 respectively).

CALCULATIONS:

T1 = ____________________

T2 =____________________

S1 =____________________

S2 = ____________________

∆T = T2 - T1 =___________________

∆S = S2 - S1 =____________________
Conc. of Standard = 2mg/dl

Creatinine (mg/dl) = ∆T
 ------ x Conc. Of Standard
∆S

Creatinine (mg/dl) = ______________