This document discusses creatinine and creatinine clearance as measures of kidney function. It describes how creatinine is produced in the body and excreted by the kidneys, and how measuring levels of creatinine in the blood and urine can provide information about glomerular filtration rate and kidney health. Specifically, creatinine clearance can be used as an indicator of glomerular filtration rate, since creatinine is produced at a constant rate and freely filtered by the kidneys. Both high and low levels of blood creatinine can indicate kidney abnormalities. The document also outlines the procedure for determining creatinine levels in samples.

1. Creatinine and Creatinine
Clearance
MOSTAFA SABRY ABDULLAH
DEMONSTRATOR DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, AL- AZHAR UNIVERSITY

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. 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. 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. 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).

7. 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.

8. 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.

9. 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.

10. (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.

11. 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.

12. 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.

13. 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-

14. 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.

15. 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: