Creatinine Clearance (CrC), Glomerular Filtration Rate (GFR)

Sample

1. 24 hours of urine is collected along with serum (clotted blood 3-5ml).
   1. When start urine collection notes the time and discards the first sample of urine. When 24 hours completed, then empty the bladder, last urine sample in the same urine container.
2. Refrigerate the urine during collection or keep on ice.
3. Collect the blood at the mid of urine collection.

Precautions

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

Indications

1. Creatinine clearance reflects the Kidneys 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 the renal functions like:
   1. Obstruction of the kidney.
   2. Acute or chronic renal failure.
   3. Dysfunction due to other causes like heart failure.

Pathophysiology

1. 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 the muscle mass, which fluctuates very little.

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

6. The amount of blood to be filtered is decreased in renal artery atherosclerosis, dehydration, and shock.
7. The ability of filtration by glomeruli will be decreased in glomerulonephritis, acute tubular necrosis, and other primary renal diseases.
8. If one kidney is knocked out then another kidney is normal, can compensate for the filtration, and GFR will be in the normal limit.
9. Creatinine clearance depends upon:
   1. With each decade of life, CrC decreases 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 the people will also affect the CrC.
      1. decrease muscle mass will give decreased values.
   4. 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.

Creatinine Clearance

1. 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.
   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:

• Formula to calculate the Creatinine clearance: Urine volume X urine creatinine/plasma creatinine.

Corrected Creatinine clearance

 Example if   U = Urine creatinine in mg/dL 

V  = urine output in 24 hours (1440 minutes)

P = Plasma or serum creatinine in mg/dL

A = Body surface area in squamous meter

1. U = number of mg /dL of creatinine excreted in the urine in 24 hours.
2. V = volume of urine in mL per minute.
3. P = serum creatinine mg/dL.
4. 1.73/A is a body surface area.

Procedure

1. Can collect 2 hours sample of the urine. Because 24 hours collection is not as accurate as 2 hours.
2. For good urine outflow, gives 500 ml of water  10 to 15 minutes before the start of the collection.
3. Completely empty the bladder and discard this urine.
4. 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.

Interfering factors

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

Normal value

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 ∼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 6.5 mL/min/decade  of life after the age of 20 years with 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 the plasma.

Increased values:

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

Decreased values:

1. When done with all precautions then it is a very sensitive indicator of decreased glomerular filtration rate.
   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.

 

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