Creatinine (Serum Creatinine)

Sample

1. This test is done on serum(clotted blood 3-5 ml) or plasma.
2. The plasma may be prepared in fluoride or heparin.
   • Flouride or heparin are not suitable for the enzymatic methods of creatinine.
3. The sample is stable for 24 hours when kept at 4 °C.
4. The non-fasting sample is acceptable.

Precautions

1. No preparation needed and the random sample can be taken.
2. Lipemic and hemolyzed samples give a falsely high level.
3. Heparin and fluoride are not good for the enzymatic procedure.
4. Excessive exercise and a high meat diet increase the level.
5. Drugs may increase the level like gentamicin, cimetidine, chemotherapy (cisplatin),

Purpose of the test (Indications)

1. Creatinine level is done to assess kidney function.
2. creatinine can be advised to see any effect of blood pressure or diabetes on the kidney.
3. Creatinine is advised to monitor renal diseases.
4. Creatinine may be measured in amniotic fluid to assess the gestational (fetal) age and (fetal-maturity index), and cephalosporins.

Pathophysiology

1. Creatinine is the end product of catabolism of creatine phosphate.
   1. Free creatinine is a waste product of creatine metabolism, is present in all body fluids and secretions.
   2. It is freely filtered by the glomerulus.
   3. There is diurnal variation when it is low at 7 AM and high at 7 PM.
   4. There is a slight increase after the meal and especially after the meat in the diet because a small amount is present in the meat.
   5. There is very little effect on liver function.
2. Creatine phosphate is used in the contraction of skeletal muscles, by providing the energy.
   1. Creatinine is the waste product formed in the muscles from high energy compound creatine phosphate.

3. The daily production of creatine and creatinine is dependent upon the muscle mass.
   1. The daily excreted creatinine is the function of muscle mass and is not dependent upon:
      1. Age.
      2. Sex.
      3. Diet.
      4. Exercise.
      5. Women excrete less creatinine than men because of less muscle mass.
      6. The daily excretion of the creatinine is relatively constant and is ±15% for a person per day.
      7. Creatinine excretion is not affected by protein metabolism or other external factors.
      8. So serum creatinine is the best measure of glomerular function (filtration).
      9. Creatinine is raised only when the 50% function of the kidney is lost.
      10. There is a minimal amount of creatinine in the urine from tubular secretion.
      11. Creatinine amount in the urine increases as the creatinine concentration rises in the blood.

4. Creatinine is entirely excreted by the kidneys so directly proportional to the kidney function.

1. 1. Creatinine level remains normal with the normal excretory function of kidneys.
      1. Creatinine is excreted by the glomeruli as the filtrate (15 to 20% of the plasma creatinine) and then it is not absorbed by the tubules.
      2. If there is any problem with glomerular filtration function then its level will increase in the blood.
      3. Creatinine is a by-product of skeletal muscle creatine phosphate metabolism.
      4. Creatinine is filtered across the glomerular filtration barrier and enters the bowman space. Now it is not reabsorbed, secreted, or metabolized by the tubular cells. So creatinine excreted in the urine per minute is equal to the amount of creatinine filtered in the bowman space.

4. 1. So renal disorders of kidneys give rise to increase in creatinine level like:
      1. Glomerulonephritis.
      2. Acute tubular necrosis.
      3. Pyelonephritis.
      4. Urinary obstruction.
5. Creatinine is a more specific and sensitive parameter of renal function and renal disease than blood urea nitrogen.
   1. This is specific for renal function and gives an idea about renal dysfunction.
6. This is not a sensitive indicator of early renal disease.
7. For a 50% reduction in GFR, serum creatinine level will be double.
8. BUN/creatinine ratio is important to evaluate the renal function.
   1. Normal in adult = 6 to 25
   2. Optimum level = 15.5

Normal

Source 1

Age	mg/dL
Cord blood	0.6 to 1.2
Newborn 1 to 4 day	0.3 to 1.0
Infants	0.2 to 0.4
Child	0.3 to 0.7
Adolescent	0.5 to 1.0	Male	Female
18 to 60 year		0.9 to 1.3	0.6 to 1.1
>90 year		1.0 to 1.7	0.6 to 1.3

• To convert to SI unit x 88.4 = µmol/L

Source 5

• Child = 0.3 to 0.7 mg/dl
• Adult = 0.5 to 1.0 mg/dl
• 18-60 years :
  • male = 0.9 to 1.3 mg/d
  • Female = 0.6 to 1.2 mg/dl
• Above 90 years
  • Male =1.0 to 1.7 mg/dl
  • Female = 0.6 to 1.3 mg/dl

Source 6

1. Adult
   1. Malle = 0.6 to 1.0 mg/dL  (53 to 106 µmol/L)
   2. Female = 0.5 to 1.1 mg/dL  (44 to 97 µmol/L)
   3. Elderly = Decrease in muscle masses cause the decreased value
2. Adolescent = 0.5 to 1.0 mg/dL
3. Child = 0.3 to 0.7 mg/dL
4. Infants = 0.2 to 0.4 mg/dL
5. Newboen = 0.3 to 1.2 mg/dL

Other source

Urinary creatinine 

• Male = 14 to 26 mg/Kg/day  (124 to 230 µmol/Kg/day).
• Female = 11 to 20 mg/Kg/day  (97 to 177 µmol/Kg/day).
• Creatinine excretion in the urine decreases with age.

Serum creatinine and creatinine clearance with the condition of the patient:

Serum creatinine mg/dL	Creatinine clearance mL/minute	The condition of the patient
0.6 to 1.3	100 ± 20	normal person
1.4 to 2.4	61 to 99	still Seen in an active person
2.5 to 4.9	24 to 60	difficulty in performing physical activity
5.0 to 7.9	12 to 23	the patient cannot do daily activity
8 to 12	7 to 12	acidosis and severe limitation of the activity
>12	6 or less	patient in a coma and disorientated

Increased creatinine may be due to three causes:

1. Pre-renal.
2. Renal.
3. Post-renal.
4. Pre-renal factors for raised serum creatinine are:
   1. Congestive heart failure.
   2. Shock.
   3. Salt and water depletion due to:
      1. Vomiting.
      2. Diarrhea.
      3. GIT fistulas.
      4. Increased use of diuretics.
      5. Uncontrolled diabetes mellitus.
      6. Diabetes insipidus.
      7. Excessive sweating (decreased salt intake).
5. Renal factors for raised serum creatinine are:
   1. Damage to:
      1. Glomerulus.
      2. Tubules.
      3. Interstitial tissue.
      4. Blood vessels.
6. Post-renal factors for raised serum creatinine are:
   1. Benign prostatic hyperplasia.
   2. Neoplasia compressing the ureter.
   3. Calculi obstructing the ureter.
   4. Congenital abnormalities obstructing or compressing the ureter.

The increased creatinine level is seen in:

1. Renal function impairment both acute and chronic diseases.
2. Postrenal obstruction of urine.
3. Decrease in the blood perfusion because of any reason.
4. Gigantism and Acromegaly.
5. Injury to the muscles (Rhabdomyolysis).
6. Myasthenia gravis.
7. Poliomyelitis.
8. Muscular dystrophy.
9. Dehydration due to loss of body fluids.
10. May be seen in pregnancy during eclampsia and preeclampsia.

The decreased creatinine level is seen in:

1. Old-age.
2. Decreased muscle mass.
3. Pregnancy especially in the first and second trimester.
4. Advanced and severe liver disease.
5. inadequate dietary intake.

Drugs leading to an increased level of creatinine:

1. Gentamicin.
2. cimetidine.
3. Heavy metals chemotherapy e.g. Cisplatin.
4. Nephrotoxic drugs like Cephalosporin e.g. Cefoxitin.

Interfering factors:

1. Ascorbic acid can increase creatinine levels.
2. A diet high in protein like meat can increase the level.

• The critical value is >4 mg/dL suggests severe renal disease.

 

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