Creatinine Clearance (CrC)

Sample

1. 24 hours of urine is collected along with serum (clotted blood 3-5ml).
   1. When starting urine collection, note the time and discard the first urine sample. When 24 hours are completed, then empty the bladder’s last urine sample in the same urine container.
2. Refrigerate the urine during collection or keep it on ice.
3. Collect the blood in the mid of urine collection.
4. 2-hour collection of urine also correlates with the 24-hours of urine.
   1. 2-hour collection preferably be done in the early morning fasting patient because in the postprandial state there is an increase in the blood creatinine and urine level (10% to 40%).

Precautions for Creatinine Clearance (CrC)

1. The patient should be hydrated so that there is >2 mL urine output per minute.
2. Avoid coffee, tea, and drugs during the test.
3. Stop the medication (Drugs) like cortisone or ACTH treatment.
4. Exercise increases creatinine levels.
5. An incomplete collection of urine gives a false value.
6. Meat rich diet increases creatinine.
7. Drugs. like aminoglycosides, e.g., gentamicin, heavy metals, and nephrotoxic drugs increase the creatinine level.
8. The test becomes less accurate when GFR falls below 10 mL/min.
9. In the case of high plasma protein, creatinine secretion is increased, leading to a marked overestimation of GFR.

Indications for Creatinine Clearance (CrC)

1. Creatinine clearance reflects the Kidney’s ability to excrete creatinine.
2. Creatinine clearance is used to measure the glomerular filtration rate (GFR) of the kidney.
3. This test will give information on renal functions like:
   1. Obstruction of the kidney.
   2. Acute or chronic renal failure.
   3. Dysfunction due to other causes like heart failure.
4. In acute glomerulonephritis, it is used to follow the therapeutic response to the treatment.
5. Creatinine clearance can be used to differentiate between glomerular disease compared to diffuse chronic structural changes.
6. This is a good test to assess the overall renal functional damage.

Pathophysiology of Creatinine clearance

1. Creatinine is a metabolic product of creatine-phosphate dephosphorylation in the muscles.
2. Creatinine is a breakdown of creatine phosphate, which has an important role in the contraction of muscles.
   1. The daily production of creatine and creatinine depends upon muscle mass, which fluctuates very little. Most of the creatinine production is stable thorough out the day.

3. Creatinine is freely and mainly excreted by the kidney, so this will reflect the filtration power of the kidney.
   1. Excretion of creatinine by the kidney is a combination of glomerular filtration, which is 70% to 80%, and another fraction is by tubular secretion.
   2. Creatinine excretion by the kidney will depend upon the number of a millimeter of filtrate (urine) per minute is called the glomerular filtration rate (GFR ).
4. The filtrate will depend upon the amount of blood to be filtered.
5. Further filtration will depend upon the ability of the glomeruli to act as a filter.
6. Creatinine clearance is a measure of GFR.
   1. Creatinine clearance is roughly equal to the glomerular filtration rate (GFR).
   2. Plasma creatinine of 15% to 20% is filtered, and the rest goes back to the systemic circulation and renal vein.
   3. Amount filtered = Amount excreted.
      1. GFR x Plasma creatinine  =   Urine creatinine x Urine volume

7. The amount of blood to be filtered decreases in renal artery atherosclerosis, dehydration, and shock.
8. The ability of filtration by glomeruli will be decreased in glomerulonephritis, acute tubular necrosis, and other primary renal diseases.
9. If one kidney is knocked out, then another kidney is normal, can compensate for the filtration, and GFR will be within the normal limit.
10. Creatinine clearance depends upon the following:
    1. With each decade of life, CrC decreases by 6.5 mL/min because of a decrease in GFR.
    2. Urine collection is for 24 hours, so any error in the collection will give false results.
    3. Muscle mass varies among people and will also affect the CrC.
       1. Decreasing muscle mass will give decreased values.
    4. Ingestion of a large amount of meat for a time will increase the CrC.

Glomerular filtration rate (GFR)

Definition of GFR:

1. GFR is defined as the number of millimeters of urine filtrate the kidneys make per minute.
2. Normally this amount is around 130 mL/minute and 180 liters per 24 hours.
3. GFR depends upon the effective filtration pressure in the glomeruli and the rate of renal blood flow.
4. GFR is described as = mL/min/1.73 m².

Average or estimated GFR:

Age of the person in years	Average GFR = mL/min/1.73 m2
20 to 29	116
30 to 39	107
40 to 49	99
50 to 59	93
60 to 69	85
70 and above	75

Creatinine Clearance (CrC)

Definition of creatinine clearance:

1. It is defined as the quantity of blood cleared of a substance per unit of time and depends on the substance’s plasma concentration and the kidney’s excretion rate, which reflects GFR and renal plasma flow.
   1. Creatinine clearance is a measure of the glomerular filtration rate.
2. Urine and serum creatinine levels are measured, and the creatinine clearance rate is calculated.

Creatinine clearance is calculated as follows:

Formula to calculate the Creatinine clearance:

• Urine volume X urine creatinine/plasma creatinine.
  • Creatinine clearance = UV/P
    • P = Serum creatinine in mg/dL
    • V = Volume of urine in mL/minute.
    • U = Number of mg/dL of creatinine excreted in the urine in 24 hours (reference Mosby’s manual of diagnostic and laboratory tests).
• Creatine clearance uncorrected formula:

1. The corrected creatinine clearance formula may be simplified = Measured creatinine clearance x 1.73 / Patient’s surface area (sq m).

Example:

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 meters (1.73/A is a body surface area).

1. There are various simplified formulas for the calculation of creatinine clearance.

The Cockcroft-Gault formula is simple and reliable:

Procedure for creatinine clearance

1. 2-Hours collection method:
2. Can collect2 hours sample of urine because 24 hours collection is not as accurate as 2 hours.
3. For good urine outflow, gives 500 ml of water  10 to 15 minutes before the start of the collection.
4. Completely empty the bladder and discard this urine.
5. 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.
6. Also, check the serum creatinine level.

Interfering factors for creatinine clearance

1. With increasing age, creatinine clearance also decreases because of a decrease in GFR.
2. An incomplete collection of urine will give false values.
3. Decreased muscle mass gives decreased values.
4. Increased ingestion of meat will increase Creatinine clearance.
5. Exercise may increase creatinine.
6. drugs like gentamicin, cimetidine, and cephalosporin may give rise to an increase in the level.

The normal value of the creatinine clearance test

Source 1

Age	mL /min / 1.73 m2
0 to 1 year	72
one year	45
2 year	55
4 year	71
5 year	73
6 year	64
7 year	67
8 year	72
9 year	83
10 year	89
11 year	92
12 year	109
13 to 14 year	86
		Male	Female
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 ∼by 6.5 mL/min.

• To convert to SI units x 0.00963 = Mean creatinine Clearance  mL/s/m².

Source 2

• Male = 97 to 137 ml/min.
• Female = 88 to 128 ml/min.
• Children =70 to 140 ml/ min.
• Newborn = 40 to 65 ml / min.

Source 6

Adult <40 years of age

1. Male = 107 to 139 mL/min  (1.78 to 2.32 ml/sec)
2. Female = 87 to 107 mL/min (1.45 to 1.78 mL/sec)
   1. value decreases by 6.5 mL/min/decade of life after the age of 20 years with a decline in GFR.

Newborn = 40 to 65 mL/min

Another source

• 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 in the plasma.

Increased values of creatinine clearance:

1. This has no clinical significance; we suspect some errors in the collection procedure.
   1. Pregnancy
   2. Exercise.
   3. High cardiac output syndrome.

Decreased values of creatinine clearance (CrC):

1. It is a very sensitive indicator of decreased glomerular filtration rate when done with all precautions.
   1. Diseases of the kidney with impaired renal function.
   2. Congestive heart failure.
   3. Cirrhosis with ascites.
   4. Shock.
   5. Dehydration (loss of body fluids).
   6. Bladder outlet obstruction.

Drawbacks of creatinine clearance:

1. There are certain drawbacks of creatinine clearance.
2. The reference limit is established for young adults, which is 90 to 120 mL/minute.
3. GFR is found to decrease with age. There are references that 4 ml/minute decreases for each decade after the age of 20 years.
4. There are studies where it was found that creatinine clearance is as low as 50 mL/minute in clinically healthy elderly persons.
5. Creatinine production and excretion also decrease with age, although serum creatinine is in the normal range.
6. There are several nonrenal factors affecting creatinine clearance.
7. An accurate collection of urine is needed.
8. Creatinine clearance is better than urea clearance and has replaced urea clearance.
9. Creatinine comes from the muscles, so the individual’s muscle mass also affects the test.
10. An old person with decreased muscle mass with chronic renal failure or malnourished persons can produce decreased creatinine clearance values.
11. Dietary meat in abundant quantity may increase serum creatinine, decreasing creatinine clearance.
12. ketones in the blood may interfere with Jaffe’s biochemical estimation of creatinine.
13. The major drawback is its nonspecificity when creatinine clearance decreases, which can not be used to differentiate the etiology of the abnormality.

Advantages of creatinine clearance test:

1. Creatinine clearance is still a better test than urea clearance.
2. Creatinine clearance is reported as one of the most sensitive tests to find a renal failure warning.

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