Kidney Function Tests

(KFTs)
Objectives

Upon completion of lectures, students should be able to:

1. know the physiological functions of the kidney.
2. describe the structure and function of the nephron.
3. identify the biochemical kidney function tests with special
emphasis on when to ask for the test, the indications and
limitations of each kidney function tests.
4. interpret the kidney function tests properly.
Contents:

• Functional units
• Kidney functions
• Routine kidney function tests (KFTs):
• Serum creatinine
• Creatinine clearance
• Cockcroft-Gault formula for GFR estimation
• Serum Urea
Functional units :

 The nephron is the functional unit of the kidney

 Each kidney contains about 1,000,000 to 1,300,000 nephrons.
 The nephron is composed of glomerulus and renal tubules.
 The nephron performs its homeostatic function by ultra filtration at
glomerulus and secretion and reabsorption at renal tubules.
Representation of a nephron and its blood supply
Each nephron is a complex apparatus comprised of
five basic parts:

1. Glomerulus: functions to filter incoming blood.

• Factors facilitate filtration:

• high pressure in the glomerular capillaries, which is a

result of their position between two arterioles.

• the semipermeable glomerular basement membrane,

which has a molecular size cutoff value of
approximately 66,000 Da.

The volume of blood filtered per minute is the glomerular

filtration rate (GFR), and its determination is essential in
evaluating renal function.
Each nephron is a complex apparatus comprised of
five basic parts:

2. Proximal convoluted tubule:

• Returns the bulk of each valuable substance back to

the blood circulation.
• 75% of the water, sodium, and chloride.
• 100% of the glucose (up to the renal threshold)
• almost all of the amino acids, vitamins, and proteins
• varying amounts of urea, uric acid, and ions, such as
magnesium, calcium and potassium.
With the exception of water and chloride ions, the
process is active; that is, the tubular epithelial cells use
energy to bind and transport the substances across the
plasma membrane to the blood.

• Secretes products of kidney tubular cell metabolism,

such as hydrogen ions, and drugs, such as penicillin.
Each nephron is a complex apparatus comprised of
five basic parts:

3. Loop of Henle:

• Facilitates the reabsorption of water, sodium, and

chloride.

The osmolality in the medulla in this portion of the nephron

increases steadily from the corticomedullary junction inward
Each nephron is a complex apparatus comprised of
five basic parts:

4. Distal convoluted tubule:

• The filtrate entering this section of the nephron is

close to its final composition.

• Effects small adjustments to achieve electrolyte and

acid-base homeostasis (under the hormonal control of
both antidiuretic hormone (ADH) and aldosterone).

The distal convoluted tubule is much shorter than the proximal

tubule, with two or three coils that connect to a collecting duct.
Each nephron is a complex apparatus comprised of
five basic parts:

5. Collecting duct:

• The collecting ducts are the final site for either

concentrating or diluting urine.

• The hormones ADH and aldosterone act on this

segment of the nephron to control reabsorption of
water and sodium.

• Chloride and urea are also reabsorbed here.

Kidney functions :
 Regulation of :
- water and electrolyte balance.
- acid base balance.
- arterial blood pressure.
 Excretion of metabolic waste products and foreign
chemicals.
 Hormonal Function: Secretion of erythropoietin &
activation of vitamin D and activation of angiotensinogen
by renin
 Metabolic Function: site for gluconeogenesis
 Why to test the renal functions?

• Many diseases affect renal function.

• In some, several functions are affected.

• In others, there is selective impairment of glomerular function or

one or more of tubular functions.

• Most types of renal diseases cause destruction of complete

nephron.
Routine KFTs include the measurement of :
• Serum creatinine (Cr).
• Creatinine clearance.
• Serum urea.

Both serum Cr and creatinine clearance are used

as kidney function tests to :
• Confirm the diagnosis of renal disease.
• Give an idea about the severity of the disease.
• Follow up the treatment.
Serum creatinine (55-120 mol/L in adult):

• Creatinine is the end product of creatine catabolism.

• 98% of the body creatine is present in the muscles where it

functions as store of high energy in the form of creatine
phosphate.

• About 1-2 % of total muscle creatine or creatine phosphate pool

is converted daily to creatinine through the spontaneous, non
enzymatic loss of water or phosphate.
Serum creatinine (55-120 mol/L in adult):

• Creatinine in the plasma is filtered freely at the glomerulus and

secreted by renal tubules (10 % of urinary creatinine).

• Creatinine is not reabsorbed by the renal tubules.

• Plasma creatinine is an endogenous substance not affected by

diet.

• Plasma creatinine remains fairly constant throughout adult life.

 Creatinine clearance:

• The glomerular filtration rate (GFR) provides a useful index of

the number of functioning glomeruli.

• It gives an estimation of the degree of renal impairment by

disease.
 Accurate measurement of GRF by
clearance tests requires determination
of the concentration in plasma and urine
of a substance that is:
• Freely filtered at glomeruli.
• Neither reabsorbed nor secreted by tubules.
• Its concentration in plasma needs to remains constant
throughout the period of urine collection.
• Better if the substance is present endogenously.
• Easily measured.

Creatinine meets most of these criteria.

• Creatinine clearance is usually about 110 ml/min in the 20-40
year old adults.

• It falls slowly but progressively to about 70 ml/min in individuals

over 8o years of age.

• In children, the GFR should be related to surface area, when this

is done, results are similar to those found in young adults.
• Clearance is the volume of plasma cleared from the substance
excreted in urine per minute.

• It could be calculated from the following equation:

Clearance (ml/min) = U  V
P
U = Concentration of creatinine in urine mol/l
V = Volume of urine per min
P = Concentration of creatinine in serum mol/l
 Cockcroft-Gault Formula
for Estimation of GFR
 As indicated above, the creatinine clearance is measured by
using a 24-hour urine collection, but this does introduce the
potential for errors in terms of completion of the collection.

 An alternative and convenient method is to employ various

formulae devised to calculate creatinine clearance using
parameters such as serum creatinine level, sex, age, and
weight of the subject.
 An example is the Cockcroft-Gault Formula:

K  (140 – age)  Body weight

GFR = ──────────────────
Serum creatinine (mol/L)

 where K is a constant that varies with sex:

1.23 for male & 1.04 for females.

 The constant K is used as females have a relatively lower

muscle mass.
 Cockcroft-Gault Formula
for Estimation of GFR: Limitations

 It should not be used if

 Serum creatinine is changing rapidly

 the diet is unusual, e.g., strict vegetarian
 Low muscle mass, e.g., muscle wasting
 Obesity
Serum Cr is a better KFT than creatinine
clearance because:

• Serum creatinine is more accurate.

• Serum creatinine level is constant throughout adult life

Creatinine clearance is only recommended in the

following conditions:

• Patients with early ( minor ) renal disease.

• Assessment of possible kidney donors.
• Detection of renal toxicity of some nephrotoxic drugs.
Normal adult reference values:
Urinary excretion of creatinine is 0.5 - 2.0 g per 24 hours in a
normal adult, varying according to muscular weight.
- Serum creatinine : 55 – 120 mol/L
- Creatinine clearance: 90 – 140 ml/min (Males)
80 – 125 ml/min (Females)

A raised serum creatinine is

a good indicator of impaired renal function

But normal serum creatinine

does not necessarily indicate normal renal function as
serum creatinine may not be elevated until GFR has fallen
by as much as 50%
Serum Urea ( 2.5-6.6 mmol/L) in adult:
Urea is formed in the liver from ammonia released from
deamination of amino acids.

As a kidney function test, serum urea is inferior

to serum creatinine because:
• High protein diet increases urea formation.
• Any condition of  proteins catabolism (Cushing syndrome,
diabetes mellitus, starvation, thyrotoxicosis)  urea
formation.
• 50 % or more of urea filtered at the glomerulus is passively
reabsorbed by the renal tubules.
Normal values of Internal Chemical Environment
controlled by the Kidneys:

SODIUM 135 to 145 mEq/L

POTASSIUM 3.5 to 5.5 mEq/L
CHLORIDES 100 to 110 mEq/L
BICARBONATE 24 to 26 mEq/L
CALCIUM 8.6 to 10 mg/dl
MAGNESIUM 1.6 to 2.4 mg/dl
PHOSPHORUS 3.0 to 5.0 mg/dl
URIC ACID 2.5 to 6.0 mg/dl
pH 7.4
CREATININE 0.8 to 1.4 mg/dl

BUN (Blood Urea Nitrogen) 15 to 20 mg/dl

References :

 Clinical Chemistry: Techniques, Principles, Correlations. 6th ed,

Michael L. Bishop, Edward P. Fody, Larry E. Schoeff. C hapter 26,
2010, pp 557-577