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Azotemia is a medical condition
characterized by a higher than normal
blood level of urea or other nitrogen
containing compounds in the blood as a
result of insufficient filtering of the blood
by the kidneys or inability of the kidney
to excrete these compounds
Uremia is a toxic condition resulting
from renal failure, when kidney
function is compromised and urea
and waste products normally
excreted in the urine, is retained in
the blood.
Acute renal failure (ARF) is a rapid loss of renal
function resulting in retention of nitrogenous (urea
and creatinine)and non nitrogenous waste
Depending on the severity and duration of the renal
dysfunction, this accumulationis accompanied by
metabolic disturbances, such as metabolic acidosis
and hyperkalaemia, changes in body fluid balance,
and effects on many other organ systems.
It can be characterised by oliguria.
The first consensus definition of
acute renal failure (RIFLE)
Consensus criteria for the diagnosis of ARF
Risk: serum creatinine increased 1.5 times
OR urine production of <0.5 ml/kg body
weight for 6 hours
Injury: creatinine 2.0 times OR urine
production <0.5 ml/kg for 12 h
Failure: creatinine 3.0 times OR creatinine
>355 mol/l (with a rise of >44) or urine
output below 0.3 ml/kg for 24 h
Loss: persistent ARF or more than four
weeks complete loss of kidney function
End Stage in relation to kidney function
Chronic renal failure is a gradual and
progressive loss of the ability of the
kidneys to excrete wastes, concentrate
urine, and conserve electrolytes.
Chronic renal failure usually occurs over a
number of years as the internal
structures of the kidney are slowly
In the early stages, there may be no
symptoms. In fact, progression may be so
gradual that symptoms do not occur until
kidney function is less than one-tenth of
Functions of Kidney
Has three major functions
Excretion of wastes.
Maintenance of ECF volume & concentration
Hormone synthesis
Kidneys receive about 25% of cardiac
Normal GFR is 120 ml/min 170 L/24 hrs
Urine production is 1 2 L/24 hrs.
Impaired kidney function may be
"prerenal", "renal", or "postrenal".
Prerenal azotemia results from
underperfusion of the kidney: dehydration,
hemorrhage, shock, congestive heart
failure; glomerulonephritis is likely also to
be "prerenal" if mild, since it comprmises
renal blood flow more than tubular function
Renal azotemia has several familiar causes:
acute tubular necrosis, chronic interstitial
nephritis, some glomerulonephritis, etc.
Postrenal azotemia results from obstruction
of urinary flow: prostate trouble, stones,
surgical mishaps, tumors
To evaluate kidney function and monitor the
effectiveness of dialysis and other treatments related
to kidney disease or damage.
This test measures the amount of urea nitrogen in the
Nitrogen, in the form of ammonia, is produced in the
liver when protein is broken into its component parts
and metabolized.
The nitrogen combines with other molecules in the liver
to form the waste product urea.
The urea is then released into the bloodstream and
carried to the kidneys, where it is filtered out of the
blood and excreted in the urine.
Since this is an ongoing process, there is usually a
small but stable amount of urea nitrogen in the blood.
What does the test result mean?
Increased BUN levels suggest impaired kidney function.
This may be due to acute or chronic kidney disease,
damage, or failure.
It may also be due to a condition that results in
decreased blood flow to the kidneys, such as
congestive heart failure, shock, stress, recent heart
attack, or severe burns.
It may be due to conditions that cause obstruction of
urine flow, or to dehydration.
BUN concentrations may be elevated when there is
excessive protein catabolism (breakdown),
significantly increased protein in the diet, or
gastrointestinal bleeding.
Lack of protein (celiac disease, some
patients with nephrotic syndrome)
Severe liver disease (end-stage
cirrhosis, yellow atrophy, really bad
hepatitis, halothane or acetaminophen
toxicity, enzyme defects)
Overhydration (iatrogenic, psychogenic
Both decreased and increased BUN
concentrations may be seen during a
normal pregnancy.
BUN x 2.14 = blood urea
BUN = Blood Urea/2.14
Reference Range:
Blood urea: 3.3 6.7 mmol/l
(10 50 mg/dl)
BUN: 2.9 - 8.9 mmol/L
(8 - 25 mg/dL )
Creatinine is a waste product produced in
muscles from the breakdown of a compound
called creatine.
Creatine is part of the cycle that produces
energy needed to contract muscles.
Creatinine are produced at a relatively
constant rate.
Almost all creatinine is excreted by the
kidneys, so blood levels are a good measure of
how well kidneys are working.
The quantity produced depends on the size of
the person and their muscle mass.
For this reason, creatinine concentrations will
be slightly higher in men than in women and
What does the test result mean?
Increased creatinine levels in the blood suggest
diseases or conditions that affect kidney function.
These can include:
damage to or swelling of blood vessels in the kidneys
(glomerulonephritis) caused by, for example, infection
or autoimmune diseases;
bacterial infection of the kidneys (pyelonephritis);
death of cells in the kidneys small tubes (acute tubular
necrosis) caused, for example, by drugs or toxins;
prostate disease, kidney stone, or other causes of
urinary tract obstruction; or
reduced blood flow to the kidney due to shock,
dehydration, congestive heart failure, atherosclerosis,
or complications of diabetes.
Creatinine can also increase temporarily as a result of
muscle injury.
Drugs such as aminoglycosides (gentamicin) can
cause kidney damage and so creatinine is

Other drugs, such as cephalosprins (cefoxitin),

may increase creatinine concentration without
reflecting kidney damage.

Moderate exercise will not affect creatinine levels.

Low levels of creatinine are not common

They can be seen with conditions that result in

decreased muscle mass.

Creatinine levels are generally slightly lower

during pregnancy.
Creatinine clearance
Creatinine clearance is widely used to
approximate glomerular filtration rate.
It gives a more precise indication of the
state of the kidneys.
The GFR is expressed in ml/min/1.73 m2
This is an indication that the GFR needs
to be corrected for the body surface area
GF Recorrected = GFR x 1.73/ BSA
BSA can be calculated on the basis of weight
and height.
This test measures the amount of
creatinine in the blood and urine to help
evaluate the kidneys filtering ability.
The amount of creatinine taken from the
blood depends on the filtering ability of
the glomeruli and the rate at which blood
is carried to the kidneys.
If the glomeruli are damaged or diseased,
or if blood circulation is slowed, then less
creatinine will be removed from the blood
and released into the urine.
The creatinine clearance is a calculation
that allows a general evaluation of the
amount of blood that is being filtered in
24 hours.
How is the sample collected for
The test requires:
A 24-hour urine collection
A blood sample drawn either at the
beginning or end of the urine
Current height and weight is
required if the patient is slim or

U creatinine x 24 h urine volume

Clearance = ml/min
Plasma creatinine x 24 x 60

Reference range: 90 120 ml/min

How is it used?

It is used to help detect kidney

dysfunction and/or the presence of
decreased blood flow to the kidneys.
In patients with chronic kidney
disease or congestive heart failure
which decreases the rate of blood
flow, the creatinine clearance test
may be ordered to help monitor the
progress of the disease and evaluate
its severity.
What does the test result mean?
Any disease or condition that affects the glomeruli
can decrease the kidneys ability to clear creatinine
and other wastes out of the blood.
When this occurs, the blood creatinine level will be
increased, the creatinine excreted in the urine is
decreased and the creatinine clearance will be
A decreased creatinine clearance rate may also
occur when there is decreased blood flow to the
kidneys as may occur with congestive heart failure,
obstruction within the kidney, or acute or chronic
kidney failure.
The less effective the kidney filtration, the greater
the decrease in clearance.
Increased creatinine clearance rates may
occasionally be seen during pregnancy, exercise,
and with diets high in meat.
Patients with one dysfunctional and one
normal kidney will usually have normal
creatinine clearance rates as the
functional kidney will increase its rate of
filtration in compensation.
Creatinine clearance rates tend to fall
later in life as the glomerular filtration
rate declines.
Certain drugs, such as aminoglycosides,
cimetidine, cisplatin, and cephalosporins,
can decrease the creatinine clearance
Diuretics can increase the result.
Interpretation of GFR
Kidney Damage Description GFR Other findings
1 Kidney damage 90+ Protein or albumin in
with normal or urine are high, cells or
high GFR casts seen in urine

2 Mild decrease in 60-89


3 Moderate 30-59
decrease in GFR

4 Severe decrease 15-29

in GFR

Kidney failure < 15

Plasma creatinine and urea are relatively
insensitive assays of renal function since more
than 60% of the kidney can be destroyed before
they are significantly affected.
Urea and creatinine clearance tests measure
glomerular filtration and are commonly used to
assess renal function.
Neither give an absolutely accurate value. Urea
gives a slightly low value since it diffuses back
into the bloodstream from the proximal tubule,
whilst creatinine gives a slightly high value
because it is secreted from the proximal tubule.
Inulin would give a more accurate estimate of
glomerular function but is rarely used since it
has to be injected.
Glycosuria in a subject with a normal
blood glucose concentration implies
proximal tubular malfunction.
Water deprivation test to assess renal
concentrating ability.
Urinary acidification test to diagnose
distal renal tubular acidosis.
2 Microglobulin in urine
Hyponatremia is due to sodium loss in kidney
disease (acute tubular necrosis)
Hypernatremia is due to ARF & CFR ( GFR)
Sodium urine concentrations must be
evaluated in association with blood levels.
The body normally excretes excess sodium, so
the concentration in the urine may be
elevated because it is elevated in the blood.
It may also be elevated in the urine when the
body is losing too much sodium. In this case,
the blood level would be normal to low.
If blood sodium levels are low due to
insufficient intake, then urine concentrations
will also be low.
The most common cause of
hyperkalemia is kidney disease (ARF &
Hypokalemia is found in renal tubular
acidosis and diuretic phase of acute
renal failure.
Hypocalcemia is common in patients
with end stage renal disease but is
rarely symptomatic.

Calculate the BUN/creatinine ratio.

This is normally around 10.
Values over 10, especially over 20,
suggest prerenal azotemia rather than
acute tubular necrosis.
High values are also seen postrenal
azotemia and upper GI bleeding.
In prerenal azotemia, urine sodium is low,
the kidney responds to low blood flow by
"trying to retain all the sodium it can."
In acute tubular necrosis, urine sodium is
higher (the renal tubules are unable to
concentrate or dilute the glomerular filtrate
Urinary sodium under 20 mEq/L suggests
prerenal azotemia
Urinary sodium over 40 mEq/L suggests
acute tubular necrosis.
It is approximated by:
(Urine Na) x (Serum creatinine)
FE Na =
(Serum Na) x (Urine creatinine)

Values less than 1% indicate prerenal

Values over 2% indicate acute tubular