Creatinine Clearance (CrC), Glomerular Filtration Rate (GFR)
- 24 hours of urine is collected along with serum (clotted blood 3-5ml).
- When starting urine collection note the time and discard the first sample of urine. When 24 hours are completed, then empty the bladder, last urine sample in the same urine container.
- Refrigerate the urine during collection or keep it on ice.
- Collect the blood in the mid of urine collection.
- 2-hours collection of the urine, also correlate with the 24-hours of the urine.
- 2-hours collection preferably be done in the early morning fasting patient, because in postprandial state there is increase in the blood creatinine and urine level (10% to 40%).
- The patient should be hydrated so that there is >2 mL urine output per minute.
- Avoid coffee, tea, drugs during the test.
- Stop the medication (Drugs) like cortisone, or ACTH treatment.
- Exercise increases the creatinine level.
- An incomplete collection of the urine gives a false value.
- Meat rich diet increases creatinine.
- Drugs. like aminoglycosides e.g. gentamicin, heavy metals, and nephrotoxic drugs increase the creatinine level.
- When GFR falls below 10 mL/min, the test becomes less accurate.
- In the case of high plasma protein, creatinine secretion is increased, leading to marked overestimation of GFR.
Indications for creatinine clearance
- Creatinine clearance reflects the Kidneys ability to excrete creatinine.
- Creatinine clearance is used to measure the glomerular filtration rate (GFR) of the kidney.
- This test will give information on the renal functions like:
- Obstruction of the kidney.
- Acute or chronic renal failure.
- Dysfunction due to other causes like heart failure.
- In acute glomerulonephritis, it is used to follow the therapeutic response to the treatment.
- Creatinine clearance can be used to diffreneciate between the glomerular disease in comparison to diffuse chronic structural changes.
- This is good test to assess the overall renal functional damage.
- Creatinine is a metabolic product of creatine-phosphate dephosphorylation in the muscles.
- Creatinine is a breakdown of creatine phosphate which has an important role in the contraction of muscles.
- The daily production of creatine and creatinine depends upon the muscle mass, which fluctuates very little. Most of the creatinine production is stable thorough out the day.
- Creatinine is freely and mainly excreted by the kidney so this will reflect the filtration power of the kidney.
- Excretion of the creatinine by the kidney is a combination of glomerular filtration which is 70% to 80% and another fraction is by tubular secretion.
- Creatinine excretion by the kidney will depend upon the number of a millimeter of filtrate (urine) per minute is called glomerular filtration rate (GFR ).
- The filtrate will depend upon the amount of blood to be filtered.
- Further filtration will depend upon the ability of the glomeruli to act as a filter.
- Creatinine clearance is a measure of GFR.
- Creatinine clearance is roughly equal to the glomerular filtration rate (GFR).
- Plasma creatinine 15 to 20% is filtered and the rest goes back to the systemic circulation, renal vein.
- Amount filtered = Amount excreted
- GFR x Plasma creatinine = Urine creatinine x Urine volume
- The amount of blood to be filtered is decreased in renal artery atherosclerosis, dehydration, and shock.
- The ability of filtration by glomeruli will be decreased in glomerulonephritis, acute tubular necrosis, and other primary renal diseases.
- If one kidney is knocked out then another kidney is normal, can compensate for the filtration, and GFR will be in the normal limit.
- Creatinine clearance depends upon:
- With each decade of life, CrC decreases 6.5 mL/min because of a decrease in GFR.
- Urine collection is for 24 hours, so any error in the collection will give false results.
- Muscle mass varies among the people will also affect the CrC.
- Decreasing muscle mass will give decreased values.
- Ingestion of a large amount of meat for the time will increase the CrC.
Glomerular filtration rate (GFR)
Definition: GFR is defined as the number of millimeters of urine Filtrate made by the kidneys per minute.
- It is defined as the quantity of blood cleared of a substance per unit time and depends on the plasma concentration of the substance and excretion rate of the kidney which reflects GFR and renal plasma flow.
- Creatinine clearance is a measure of the glomerular filtration rate.
- Urine and serum creatinine levels are measured and the creatinine clearance rate is calculated.
Creatinine clearance is calculated as:
Formula to calculate the Creatinine clearance: Urine volume X urine creatinine/plasma creatinine.
- The corrected formula of creatinine clearance may be simplified = Measured creatinine clearance x 1.73 / Patients surface area (sq m).
Example if U = Urine creatinine in mg/dL (number of mg/dL of creatinine excreted in the urine in 24 hours).
V = Urine output in 24 hours (1440 minutes) (volume of urine in mL/minute).
P = Plasma or serum creatinine in mg/dL
A = Body surface area in square meter (1.73/A is a body surface area).
- There are various simplified formulas for the calculation of creatinine clearance.
- Gault and Cockcroft formula is simple and reliable.
= (140-age in years) X weight in Kg / 72 X serum creatinine (mg/dL).
Procedure for creatinine clearance
- Can collect 2 hours sample of the urine. Because 24 hours collection is not as accurate as 2 hours.
- For good urine outflow, gives 500 ml of water 10 to 15 minutes before the start of the collection.
- Completely empty the bladder and discard this urine.
- When the patient feels full bladder, then start a collection of urine for exactly 2 hours and empty the last sample into the container at the end of 2 hours.
- Also, check the serum creatinine level.
Interfering factors for creatinine clearance
- With increasing age, the creatinine clearance also decreases because of a decrease in GFR.
- An incomplete collection of urine will give false values.
- Decreased muscle mass gives decrease values.
- Increased ingestion of meat will increase the Creatinine clearance.
- Exercise may increase creatinine.
- drugs like gentamicin, cimetidine, and cephalosporin may give rise to an increase in the level.
The normal value of the creatinine clearance test
|Age||mL /min / 1.73 m2|
|0 to 1 year||72|
|13 to 14 year||86|
|20 to 29 year||94 to 140||72 to 110|
|30 to 39 year||59 to 137||71 to 121|
|After this age with each decade, Value Decreases ∼6.5 mL/min|
- To convert to SI units x 0.00963 = Mean creatinine Clearance mL/s/m2.
- Male = 97 to 137 ml/min.
- Female = 88 to 128 ml/min.
- Children =70 to 140 ml/ min.
- Newborn = 40 to 65 ml / min.
Adult <40 years of age
- Male = 107 to 139 mL/min (1.78 to 2.32 ml/sec)
- Female = 87 to 107 mL/min (1.45 to 1.78 mL/sec)
- value decreases 6.5 mL/min/decade of life after the age of 20 years with decline in GFR.
Newborn = 40 to 65 mL/min
- Male = 85 to 125 mL/min
- Females = 75 to 115 mL/min
- Effect of the age:
- 50 to 75 years = subtract 5 mL for each 5 years interval.
- Over 75 years = subtract 8 mL for each 5 years interval.
- Artifacts that lower the value is:
- Incomplete urine collection.
- Presence of Ketones, Barbiturates.
- BSP, PSP, when the level is higher in the urine than the plasma.
Increased values of creatinine clearance:
- This has no clinical significance, suspect some error in the collection procedure.
- High cardiac output syndrome.
- When done with all precautions then it is a very sensitive indicator of decreased glomerular filtration rate.
- Diseases of the kidney with impaired renal function.
- Congestive heart failure.
- Cirrhosis with ascites.
- Dehydration (loss of body fluids).
- Bladder outlet obstruction.
Drawbacks of creatinine clearance:
- There are certain drawbacks of creatinine clearance.
- The reference limit is established for young adults which are 90 to 120 mL/minute.
- GFR is found to decrease with the age. There are references that 4 ml/minute decreases for each decade after the age of 20 years.
- There are studies where it was found that creatinine clearance is as low as 50 mL/minute in clinically healthy elderly persons.
- Creatinine production and excretion also decrease with age, although serum creatinine is in the normal range.
- There are several nonrenal factors affecting creatinine clearance.
- An accurate collection of the urine is needed.
- Creatinine clearance is better than urea clearance and it has replaced the urea clearance.
- Creatinine comes from the muscles, so the muscle mass of the individual also affects the test.
- An old person with decreased muscle mass with chronic renal failure or malnourished persons can produce decreased creatinine clearance values.
- Dietary meat in abundant quantity may increase the serum creatinine and it decreases creatinine clearance.
- ketones in the blood may interfere with Jaffe biochemical estimation of creatinine.
- The major drawback is its nonspecificity when creatinine clearance is decreasing, and that can not be used to differentiate the etiology of the abnormality.
Advantages of creatinine clearance test:
- Creatinine clearance is still better test than the urea clearnace.
- Creatinine clearance is reported as one of the most sensitive test to find the renal failure warning.