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Creatinine and Creatinine Clearance


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Creatinine clearance may be used as indicator for GFR because:
Creatinine is endogenously produced.
Creatinine is released into body fluid at constant rate.
Its plasma level maintained within narrow limits.
Its plasma level not affected by dietary factors

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Creatinine and Creatinine Clearance

  2. 2. Functions of the Kidneys: (A)- Excretory functions:- Excretion of most of the undesirable end product of metabolism. Excretion of any excess of inorganic substances ingested in the diet. Excretion of the waste products including NPN, organic acids e.g. amino acids. (B)- Regulatory functions:- Mechanisms of differential Na+, H2O, Co32- reabsorption and secretion: this operates under complex system of control. (C)- Endocrine functions:- Primary:- because the kidneys are endocrine organs producing hormones e.g. prostaglandins. Secondary:- because the kidneys are the site for hormones produced or activated else where.
  3. 3. Kidney function tests: 1- Renal clearance and glomerular filtration rate Clearance = = ml / minute V = urine flow rate ml / minute P = plasma concentration of substance. U = Urine concentration of substance. 2- Assessment of glomerular permeability. 3- Measurement of non protein nitrogenous compounds (NPN) e.g., Creatinine, urea, uric acid, ammonia and amino acids.
  4. 4. Creatinine and Creatine: Synthesis of Creatine:- Creatine is synthesized in liver, kidneys and pancreas by two enzymatically mediated reactions:  Transamidination of arginine and glycine to give guanidoacetic acid.  Methylation of guanidoacetic acid in presence of S- adenosyl methionine as methyl donner to give Creatine.
  5. 5. Fate of Creatine:- a-Creatine is transported into site of usage mainly muscles and brain. b-About 1-2% of the total muscle Creatine pool is converted daily to creatinine through the non enzymatic loss of water. c-Creatine in muscle will be phosphorylated to give Creatine phosphate (High energy compound).
  6. 6. Normal values of creatinine: Serum or plasma creatinine in male is about (0.7 -1.2 mg/dl) in female is about (0.6 -1.1 mg/dl). Urinary creatinine is about: 14 – 26 mg/kg/day (1 – 3 g/day). Execration of creatinine:- Creatinine in plasma is filtered freely unchanged at the glomerulus. A small amount of it undergoes the tubular reabsorption. Up to 7-10% of urinary creatinine result from tubular Secretion, therefore the glomerulus filtration rate (GFR) was most often assessed by determining the urinary creatinine clearance.
  7. 7. Clinical significance of creatinine and creatinine clearance: Creatinine clearance may be used as indicator for GFR because:  Creatinine is endogenously produced.  Creatinine is released into body fluid at constant rate.  Its plasma level maintained within narrow limits.  Its plasma level not affected by dietary factors.
  8. 8. Abnormalities of plasma creatinine. (A)- Low plasma creatinine:  Creatinine production is determined by the size of creatine pool hence a smaller muscle mass leads to daily lower creatinine production.  Physiologically pregnancy is accompanied with decreased plasma creatinine level. Also, females and children show low plasma creatinine levels when compared with adult men.  Pathologically low plasma level of creatinine is found in wasting diseases, starvation, and in patients treated with corticosteroids due to their protein catabolic effect.
  9. 9. (B)- High plasma creatinine:- 1- Non renal causes of increased plasma creatinine include:-  a- High protein (meat) intake → temporary increase of plasma creatinine.  b- Exercise → transient increase of plasma creatinine after vigorous exercises.  c- Analytical over estimation: some analytical methods are not specific for creatinine; they measure the endogenous and exogenous interfering substances e.g. plasma acetoacetate and pyruvate.  d- Drugs e.g. salicylates and cimetidine which reduce tubular secretion of creatinine → elevating plasma creatinine level. 2- Renal causes of increased plasma creatinine include:-  a- Diseases in which there is impaired renal perfusion e.g. reduced COP (chronic obstructive pulmonary ) and in case of renal artery stenosis.  b- Diseases with loss of nephrotic functions e.g. acute and chronic glomerulo nephritis.  c- Diseases with increased pressure on the tubular side of nephrons e.g. urinary tract obstruction due to prostatic enlargement.
  10. 10. Creatinine clearance: Normally creatinine clearance is about  (105±20) ml/minute in males and  (95±20) in females.  In children, the GFR should be related to surface area. Measurement of plasma creatinine is more precise than urinary creatinine clearance due to the accuracy of urine collection is dependent in patient that gives errors.
  11. 11. Measurement of plasma creatinine better than measurement of urinary creatinine clearance because:  Plasma creatinine normally remains fairly constant throughout adult life while creatinine clearance decline with advancing age.  Plasma creatinine correlates as well with GFR as does creatinine clearance in patient with renal disease.  Plasma creatinine measurement enables progress of renal disease to be followed with better precision than creatinine clearance.  Measurement of plasma creatinine is effective in detecting early renal diseases.
  12. 12. Determination of creatinine and creatinine clearance  Principle of assay:-  Creatinine forms an amber yellow complex with alkaline picrate (picric acid + 0.75 N NaOH), which measured photometrically at 450-520 nm.  The hydroxyl ion determine the rate of the reaction and specifies to a large extent the behavior of the spectral absorbance curve of the resulting complex over a wave lengths 485 to 520 nm. Creatinine + Picric acid + OH-
  13. 13. Procedures:- Sample Standard Blank Sample 1.5 ml - - Standard - 1.5 ml - Dist H2O - - 1.5 ml 0.75 N NaOH 1 ml 1 ml 1 ml Picric acid 1 ml 1 ml 1 ml Incubate at room temperature for 30 minutes then measure at 520 nm.
  14. 14. Calculation It means ml (s) of plasma which are cleared from creatinine per minute per standard surface area. U = Urine creatinine (mg/dl). P = Plasma or serum creatinine (mg/dl). V = Urine flow rate (ml/minute). A = Body surface area (m2). 1.73/A = factor normalize clearance for average body surface area because creatinine execration is proportion to muscle mass. Serum creatinine: Urine creatinine: