Kidney and

Liver
Function
Tests
PCH 201
L6
What are Liver Function Tests (LFTs)?

• Group of clinical biochemistry laboratory

blood assays designed to give information
about the state of a patient’s liver
• It is not a single test but a profile of the number of
parameters.

• Also known as:

• The Liver Panel,
• Hepatic Function Panel
• Liver Function Panel or
• Liver Profile
 LFTs

• The term "liver function tests "is a misleading term as

many of the tests do not comment on the function of
the liver but rather pinpoint the source of the
damage.

• The LFTs measure different enzymes, proteins, and

other substances made by the liver

• Various liver disorders alter level of chemicals that

pass into bloodstream & bile as liver performs its
various functions
 Role of Liver Function Tests
• Detect/diagnose presence of liver disease
• Indicate type of liver disease
• Monitor the extent & progression of liver
disease
• Determine how well a treatment is working
• Monitor possible side effects of medicines
Roles of liver function tests

• As a part of preventive health checkup

• To diagnose liver diseases and indicate type of liver
disease
• viral hepatitis, alcoholic hepatitis, autoimmune hepatitis or liver
cirrhosis

• To monitor the efficacy of a therapy given for the

treatment of existing liver disease

• To monitor the health of the liver when a patient is

on medicines with known harmful effects on liver
 LFTs are classified as:

Excretory function tests:

• Bile pigments, salts, acids, bilirubin and BSP
Metabolic functions tests :
• Carbohydrates, Proteins, Fats
Synthetic capabilities :
• Proteins(albumin), coagulation factors
Detoxification :
• Ammonia, drugs
Tests of liver injury :
• Enzyme assays, autoimmune markers, markers of hepatitis
virus infections
 Various components of LFTs

• It is not a single test but a profile of the number of

parameters.

• The different substances are often tested at the same time

on a single blood sample, and may include the following:
• Alanine transaminase (ALT)
• Aspartate transaminase (AST)
• Alkaline phosphatase (ALP)
• Protein - Total Protein and Serum Albumin
• Bilirubin - Total, Direct and Indirect
• Gamma-glutamyl transferase (GGT)
 Enzymes involved
• ALT, AST– enzymes found within the liver
• ALP, GGT- enzymes found in the biliary tract
• Elevation of these enzymes in the blood reveals
different pathologies
• These enzymes do not tell us anything about the
function of the liver
BUT
levels show damage to the liver or damage to
the biliary tract
 1. Hepatocellular Damage

• Damage to liver cells, with or without

necrosis, causes acute release of
intracellular constituents into
bloodstream

• Detected by measuring plasma

enzymes, transaminases
– Very sensitive
 2. Biliary Tract Involvement
• Characterized by increased production &
raised plasma levels of hepatobiliary
enzymes
– Alkaline phosphatase (ALP)
– Gamma-glutamyl transferase (GGT)
• More sensitive
• Obstruction of biliary tract to bile flow
indicates cholestasis
– Condition where bile cannot flow from liver to
duodenum
• Obstructive jaundice
3. Impaired Hepatocellular Function

• Affects synthesis of albumin & coagulation

factors & bilirubin metabolism

• Hypoalbuminaemia & a prolonged

prothrombin time are detectable when
damage is extensive & prolonged
 Transaminases
• Alanine aminotransferase = ALT

• Aspartate aminotransferease = AST

• ALT & AST are present in hepatocytes & leak

into blood with liver cell damage

• Indicate hepatocellular damage

 Transaminase AST
• AST
also known as serum glutamic oxaloacetic transaminase
(SGOT)

– Mainly mitochondrial & also present in heart,

muscle, kidney & brain

– High levels seen in:

• Hepatic necrosis
• Myocardial infarction
• Muscle injury

• AST is not specific for liver damage and is measured

along with ALT to diagnose a suspected liver disease
 Transaminase ALT
ALT
• also known as serum glutamate-pyruvate
transaminase (SGPT)
• Cytosolic enzyme

• More liver-specific
– Most sensitive marker of hepatic cell damage

• Released early in liver damage & remains

elevated for weeks
 Transaminase ALT
ALT
• In hepatocelluar disease:
– ALT rises before jaundice

• Cholestatic disease
– ALT may not rise

• Many labs only measure ALT

– More specific than AST
 Alkaline Phosphatase (ALP)
• Present in canalicular & sinusoidal
membranes of liver
• Present in other tissues
– Bone, intestinal, placenta
• In normal situations bone & liver are the major
isoenzymes
– If required, origin determined by electrophoretic
separation of isoenzymes
 Alkaline Phosphatase (ALP)
High levels of ALP are seen in patients with
○ Bile duct obstruction
○ Hepatitis
○ Cirrhosis
○ Liver cancer
○ Bone diseases

• If elevated GGT as well, ALP can be presumed

to come from liver
• Raised in cholestasis from any cause
– Intra or extra hepatic
– Synthesis of ALP is increased & released into blood
 Alkaline Phosphatase (ALP)

• In cholestatic jaundice, ALP levels may

quadruple

• Highest levels due to liver disease seen with

hepatic metastases & 1o biliary cirrhosis
Alkaline Phosphatase (ALP)

For interpretation of results consider:

• Reference ranges vary with age
– Higher in childhood & adolescence
• Isoenzymes
– eg. bone, liver, intestine, malignancy
• Bile flow
Gamma-glutamyl transferase (GGT)

• Involved in amino acid transport across

membranes

• Found mainly in biliary ducts of liver

– Also kidney & pancreas
 Gamma-glutamyl transferase (GGT)

• Activity can be induced by drugs

– Phenytoin, alcohol & barbiturates
• If ALP normal a raised GGT good guide to
alcohol intake
– Mild elevations in GGT common even with small
alcohol consumption
– Does not mean liver damage if other liver
biochemistry normal
• In cholestasis GGT rises in parallel with ALP
 Gamma-glutamyl transferase
(GGT)
• While GGT is a sensitive indicator of liver disorder, in
interpretation of results remember:
• Enzyme activity is induced by a number of drugs & in
particular alcohol
• GGT leveles increased in liver diseases especially in
obstructive jaundice
• GGT levels are used as a marker of alcohol induced liver
disease & in liver cirrhosis
• Afro-Caribbeans have higher reference range
 Serum Albumin
• Plasma transport protein made in the
liver
• main protein in our blood
• Assesses protein synthesis in liver
– Marker of synthetic function
– Guide to severity of chronic liver disease
– Falling serum albumin is poor prognostic sign
– In acute liver disease albumin may be normal
 Prothrombin Time

• Assesses rate of clotting of blood

• Reflects protein synthetic function
– Marker of synthetic function of liver
– Increased PT may mean liver damage
– However, it also can be higher if certain blood-thinning
drugs, such as warfarin are used.
 Bilirubin
• Bilirubin is a substance produced during the
breakdown of red blood cells.
• passes through the liver and is excreted in stool.
•
• Higher levels of bilirubin might mean liver
damage or disease.

• Blockage of the liver ducts or certain types of

anemia also can lead to elevated bilirubin.
 Specific Liver Diseases

Acute Hepatitis
• Caused by viruses or toxins
• Cell damage detectable by plasma enzyme
estimations
• In viral hepatitis, rapid rise in transaminases
(AST & ALT) in serum occurs even before
bilirubin rise is seen
 Specific Liver Diseases
Cirrhosis
• During active cellular destruction,
transaminase levels rise, sometimes with
jaundice

• In alcoholic cirrhosis, GGT levels are elevated

Condition Enzyme Location of enzyme
Liver damage ALT Liver hepatocytes

Liver damage AST Liver

Muscle damage Muscles -- cardiac
Myocardial Infarction -- skeletal
Brain cells
Kidney

Cholestasis ALP Biliary system

Bone breakdown Bone
Pregnancy Placenta of pregnant women
Kidney
Gastrointestinal tract (GIT)
Cholestasis GGT Biliary system (cells lining the
bile duct)
Renal Function
Urinary System

Produces urine

Transports urine
towards bladder

Temporarily store
urine

Conducts urine
to exterior
 Functions of the Kidneys

1. Homeostatic functions
2. Excretory functions
3. Endocrine functions
 Functions of the kidney at a glance…..
1.Excretion of urea and other waste products,
e.g., creatinine, uric acid and metabolites of xenobiotics.
2. Maintaining water balance
3. Excretion of sodium (effect on BP)
4. Excretion of potassium (effect on heart)
5. Excretion of hydrogen ions (maintenance of pH)
6. Activation of vitamin D (effect on bone)
7. Production of erythropoietin (effect on RBCs)
8. Filtration: 180 l/day of water with all Na, Cl, sugar
and aas
9. Reabsorption: 178.5 l reabsorbed; all glc and aas
reabsorbed; most of Na and Cl reabsorbed
 Loss of kidney functions

• Patients with chronic renal disease &

impaired renal functions
– Will show defects in endocrine & excretory
functions before loss of homeostatic control

• When homeostatic functions cease, patient

is in renal failure
– Will die if there were no interventions
 Kidney Malfunction
Detected by:
• Decreased urine production
• Clinical symptoms
• Biochemical tests
Symptoms of kidney problems

Symptoms that may indicate a problem with

your kidneys include:

• high blood pressure

• blood in the urine
• frequent urges to urinate
• difficulty beginning urination
• painful urination
• swelling of the hands and feet due to a
buildup of fluids in the body
 Categories of renal failure
• Pre-renal
– Eg decreased intravascular volume

• Renal - intrarenal
– Eg acute tubular necrosis

• Post-renal – obstruction
– ureteral obstruction
Renal function tests (RFTs)
• Are a group of tests that may be performed
together to evaluate kidney (renal) function.

• Measure levels of various substances:

• several minerals
• electrolytes
• proteins
• glucose (sugar)
in the blood to determine the current health of the
kidneys.
 Role of Kidney Function Tests

• Identify renal dysfunction

• Diagnose renal disease
• Monitor disease progress
• Monitor response to treatment
 Role of Kidney Function Tests

• Detect renal damage

• Monitor functional damage, for patients with

renal disease

• Determine etiology --- cause or origin

 Limitation of Kidney Function Tests

• Each kidney has about a million nephrons

• In renal disease about half the nephrons

have to lose their functioning
– Before abnormality can be detected by
laboratory tests
 When Renal Function
Should Be Assessed
• Older age

• Family history of Chronic Kidney disease

(CKD)

• Decreased renal mass

• Low birth weight

 When Renal Function
Should Be Assessed

• Diabetes Mellitus (DM)

• Eg urine protein

• Hypertension (HTN)

• Autoimmune disease

• Systemic infections
 When Renal Function
Should Be Assessed
• Urinary tract infections (UTI)

• Nephrolithiasis
• Process of forming a kidney stone or a stone in
kidney

• Obstruction to the lower urinary tract

• Drug toxicity
 Renal Function tests

• Plasma urea and creatinine a) To assess glomerular function

• Plasma electrolytes • Glomerular filtration rate
• Urine analysis Clearance tests
•Glomerular permeability
Proteinuria

b) To assess tubular function

•Reabsorption studies
•Secretion tests
•Concentration and dilution tests
•Renal acidification

To assess renal disease To assess renal function

The tests that are part of the Kidney Function test panel are:
(a) Urine examination
(b) Serum Urea
(c) Serum creatinine
(d) Blood urea nitrogen (BUN)
(e) Calcium
(f) Phosphorus
(g) Protein
(h) Albumin
(i) Creatinine clearance
(j) Urea clearance
(k) Inulin clearance
(l) Dilution and Concentration test
(l) Serum electrolyte levels
Plasma/Serum creatinine

• Creatine is a small tripeptide found in the muscles.

• It stays in its phosphorylated form and releases energy for any burst of
muscular activity. It is released from the muscles during regular wear
and tear and is converted to creatinine.
• Unlike urea, creatinine is not a toxic waste. It is simply used as a marker
of renal function.
• Creatinine is freely filtered at the glomerulus so any problem with
glomerular filtrations has a significant effect on the excretion of
creatinine resulting in a substantial rise in serum creatinine level.

• Serum creatinine shows how well the kidneys are working.

• The amount of creatinine in the blood depends partly on the amount of
muscle tissue the body has.
• Since the production is continuous, the blood level will not
fluctuate much, making creatinine an ideal substance for
clearance test
• Men generally have higher creatinine levels than women.
• Increased serum levels are seen in renal failure and other renal
diseases
• Creatinine, however, does not increase with age, dehydration and
catabolic states (eg fever, sepsis, haemorrhage) to the same
extent as urea.
• It is also not affected by diet.
• Serum creatinine is a better indicator of renal function and more
specifically glomerular function than urea
Reference Values of Creatinine

• Adult males, 0.7 – 1.4 mg/dL

• Adult females, 0.6 – 1.3 mg/dL
• Children, 0.4 – 1.2 mg/dL.
• The kidney reserve is such that about 50% kidney function must
be lost before creatinine level in blood is raised.
• Serum level usually parallels the severity of the disease.
• Creatinine level more than 1.5 mg/dL indicates impairment of
renal function.
• Creatinine is quantitated by Jaffe’s test (alkaline picrate). -
Serum/Plasma urea

• Blood Urea Level Normal serum urea value is 20 – 40 mg/dL.

• Serum urea OR Blood Urea Nitrogen (BUN) measures the amount
of urea in the blood. Urea is a waste product (non-toxic
metabolite) made when the protein is broken down in the body,
so it’s affected by diet.
• Urea is the end-product of protein metabolism
• Serum urea is increased in all forms of kidney diseases.
• Plasma urea conc often used index of renal glomerular function
– Blood urea nitrogen (BUN)
• Urea production increased by high protein intake
• Decreased in patients with a low protein intake
• In patients with liver disease
Therefore, it is a non-specific test
As a kidney function test, serum urea is
inferior to serum creatinine because:
• Any condition of increased proteins catabolism (Cushing
syndrome, diabetes mellitus, starvation, thyrotoxicosis) increases
urea formation.
• - - High protein diet increases urea formation.
• - - 50 % or more of urea filtered at the glomerulus is passively
reabsorbed by the renal tubules.
• - Dehydration can increase urea
• Reference interval for serum urea of healthy
adults is 5-39 mg/dl
– Slightly higher in males than females.
• Non-renal factors can affect urea level
– Mild dehydration
– High protein diet
– Increased protein catabolism
– Muscle wasting as in starvation
– Reabsorption of blood proteins after a GIT
haemorrhage
– Treatment with cortisol or analogs
• Electrolytes or dissolved salts – electrically charged chemicals
that are vital to normal body processes, such as nerve and muscle
function; among other things, they help regulate the amount of
fluid in the body and maintain the acid-base balance.
• The purpose of the kidney is not just water balance and excretion
but also to maintain the electrolyte balance of our body.
• Kidneys actively reabsorb or excrete electrolytes to maintain the
electrolyte balance of the body.
• Owing to their small size almost all electrolytes are filtered at the
glomerulus.
• After filtration most of the electrolytes are absorbed back at the
tubular level but any problem at the tubular level will result in
non absorption and excessive loss of electrolytes in urine.
• Electrolytes include:
• Sodium
• Potassium
• Chloride
• Bicarbonate (Total CO2)

• Serum electrolytes that are measured for this purpose are:

• Serum Sodium levels (Na+) : 135 to 145 mmols/liter
• Serum Pottasium level (K+) : 3.5 to 5 mmols/liter
• Serum Chloride level (Cl- ) : 95 to 105 mmols/liter
Urine analysis

• Urine analysis involves the assessment of urine characteristics to aid in

disease diagnosis.
• It consists of physical observation, chemical, and microscopic examination.
• The physical inspection involves assessing color and clarity.
• The normal urine is straw-colored, while in the presence of dehydration,
urine is darker in color.
• Red urine may indicate hematuria or porphyria or could represent the dietary
intake of food like beets.
• Cloudy urine may be seen in the presence of pyuria due to urinary tract
infection.
• Specific gravity is an indicator of renal concentrating ability, which can be
measured using refractometry or chemically by the use of urine dipstick.
• The physiological range for specific gravity is 1.003 to 1.030.
• Specific gravity is increased in concentrated urine and decreased in dilute
urine.
• Urine dipstick provides qualitative analysis of different analytes in
urine using chemical analysis.

• Dipstick uses dry chemistry methods to detect the presence of

protein, glucose, blood, ketones, bilirubin, urobilinogen, nitrite,
and leukocyte esterase.
• The dipstick can be performed as a point-of-care test.
• The color changes following the interaction of the urine with the
chemical reagents impregnated on the paper of the dipstick are
compared to the color chart guide to interpret the results.
• Analytes tested on urine dipstick-protein should not be
detectable in healthy urine specimens.
• Bilirubin is not detected in normal urine.
• Glucose is not detected in healthy patients but may be seen in
diabetes mellitus, pregnancy, and renal glycosuria when the renal
threshold of 180 mg/dl is decreased.
• The presence of ascorbic acid (vitamin C) and some antibiotics
may affect results.
• Blood may be present after renal tract injury or infection, with
ascorbic acid causing a falsely negative result.
• Urine dipstick detects the globin portion of hemoglobin, and
thus cannot detect the difference between the presence of
myoglobin or hemoglobin in urine.
• Additionally, both intact red blood cells (RBC) and hemoglobinuria are
detected.
• The presence of "blood" on urine dipstick test with normal RBC indicates
rhabdomyolysis and can help differentiate it from hematuria, where RBCs
are also detected on the urine dipstick. In normal urine, RBC per high-
power field is between 0 to 3 and white blood cells (WBC) between 0 to
5.
• Ketones are present in fasting, severe vomiting, and diabetic
ketoacidosis. Urine dipstick only detects acetoacetate and acetone, not
the ketone beta-hydroxybutyrate. Bilirubin is detected in the presence of
conjugated hyperbilirubinemia.
• Urobilinogen may typically be present, but it is absent in conjugated
hyperbilirubinemia and increased in the presence of prehepatic jaundice
and hemolysis.
• Nitrite and leucocyte esterase are indicators of urinary tract infection.
Some bacteria, for example,
• Enterobacteriaceae, convert nitrates to nitrites.
• The microscopic analysis involves a wet-prep analysis of urine to
assess the presence of cells, casts, and crystals as well as micro-
organisms.
• Red blood casts usually denote glomerulonephritis, while white
blood cell casts are consistent with pyelonephritis.
• The presence of white blood cells and WBC casts indicates
infection; red blood cells indicate renal injury; RBC casts indicate
tubular damage or glomerulonephritis.
• Hyaline casts consist of protein and may occur in glomerular
disease. Fatty casts are seen in nephrotic syndrome.
• Crystals may also be identified in urine and are indicative of the
following conditions:
• Triple phosphate crystals have the "coffin-lid" appearance and can
be seen in alkaline urine and urinary tract infection.
• Uric acid crystals are needle-shaped and are associated with gout.
• Oxalate crystals are envelope-shaped and are present in ethylene
glycol poisoning or primary and secondary hyperoxaluria.
• Cystine crystals are hexagonal and are observed in cystinuria.
 Constituents of Urine

Organic constituents include:

• Urea
• Creatinine
• Glucose
• Ketone bodies
• Amino acids
• Proteins
 Constituents of Urine

Inorganic constituents include:

• Cl-
• Na+
• K+
• NH4
+

• HPO42-
• Ca2+
 Urine Colour
• Normal colour ranges from pale yellow to
deep amber
– Due to pigment urochrome
• Most changes are harmless & temporary &
due to:
– Certain foods
– Dyes in foods/drinks
– Supplements – vitamins
– Prescription drugs
 Urine Clarity
• Substances that cause cloudiness but are
NOT unhealthy include:
– Mucous
– Sperm & prostatic fluid
– Cells from skin
– Normal urine crystals
• Condition requiring attention indicated by
presence of:
– Red blood cells
– White blood cells
– Bacteria
 Chemical Examination of Urine

• Reagent strips discarded after single use

• Perform test within 1 hr after collection

• Allow refrigerated specimens to return to

room temperature
 Chemical Examination of Urine
• Dip strip in fresh urine & compare
colour of pads to chart after appropriate
time period
– Timing critical for accurate results
 Chemical Examination of Urine
• Glucose
• Presence of glucose (glycosuria) indicates that blood glucose
level has exceeded renal threshhold
• Useful to screen for diabetes

• pH
• Measure degree of acidity or alkalinity
 Chemical Examination of Urine
Bilirubin
• Presence may be an indication of liver disease,
bile duct obstruction, or hepatitis
• Samples should not be exposed to light
– False –ve result

Urobilinogen
• Degradation product of bilirubin
• Formed by intestinal bacteria
• Increased in hepatic or haemolytic disease
 Chemical Examination of Urine

Protein
• Presence of protein (protenuria) is an
important indicator of renal disease
• False –ve result can occur if:
– Urine is alkaline or dilute
– Primary protein is not albumin

Ketone Bodies
• Excreted when body metabolizes fats
incompletely
Chemical examination of urine
Specific Gravity
• Reflects kidney’s ability to concentrate
• Need concentrated urine for accurate testing
– Best is first morning sample
• Low – kidney disease
• High – certain drugs

Nitrite
• Formed by Gram –ve bacteria
– Convert urinary nitrate to nitrite
Chemical examination of urine

Blood
• Presence of blood may indicate:
– infection
– trauma to urinary tract
– or bleeding in kidneys
• False +ve mostly due to contamination
by menstrual blood
 Chemical Examination of Urine

Leucocytes
• Presence of white blood cells usually
indicates infection

• Leucocyte esterase activity is due to

presence of white blood cells in urine
Chemical examination of urine
Normal Values
• Negative results for:
– glucose
– ketones
– bilirubin
– nitrites
– leucocyte esterase
– blood
• Protein negative or trace
• pH 5.5 – 8.0
• Urobilinogen 0.2 – 1.0 Ehrlich units
Biochemical Tests for Renal Function

1. Measurement of Glomerular
Filtration
•Rate (GFR)
2. Renal tubular function tests
3. Urinalysis
Biochemical Tests for Renal Function

Measurement of GFR
• Clearance tests
• Plasma creatinine
• Urea, uric acid & β2-microglobulin
Biochemical tests for renal function
Renal tubular function tests
• Osmolality measurements
– conc of a solution expressed as total number of solute
particles per litre
• Osmotic conc
• Specific proteinurea
– Presence of protein in urine
• Glycosuria
– Presence of glucose in urine
• Aminoaciduria
– Presence of amino acids in urine
Biochemical tests for renal function

Urinalysis
• Appearance
• Specific gravity & osmolality
• pH
• Glucose
• Protein
• Urinary sediments
• Minerals
 Measurement of GFR
Urine Volume
• Depends on how much you drink & sweat.
– In health closely matched to water balance by
hormone ADH or vasopressin, AVP
• Oliguria = abnormally low urine volume <
400 mL/day
• Anuric = no or little urine < 100 mL/day
• Polyuria = >3 L/day & not drinking
 Measurement of GFR
• GFR used as index of overall excretory function
– GFR is subject to reduction with age
• Need for correct reference ranges

• GFR is estimated by measuring the urinary excretion

of a substance that is completely filtered from the
blood by glomeruli
• & it is not secreted, reabsorbed or metabolized by
renal tubules
 Measurement of GFR

• Clearance is defined as the (hypothetical)

quantity of blood or plasma completely
cleared of a substance per unit of time
– Clearance of substances that are filtered exclusively
or predominantly by glomeruli but neither
reabsorbed nor secreted by other regions of
nephron can be used to measure GFR
 Measurement of GFR
• Some substances when filtered enter tubules
& are not reabsorbed eg inulin
– 100% excreted = GFR
– inulin = gold standard for GFR
• Volume of blood from which inulin is cleared
or completely removed in 1 min
– = inulin clearance = GFR
• Measurement of inulin clearance requires
infusion of inulin into blood & is not
suitable for routine clinical use
 Measurement of GFR
• Clearance of:
– Inulin
– creatinine
– EDTA
– cystatin C

• GFR = Ux x V
Px

V = volume of urine/ 1 minute or 1

second Ux = conc of x in urine
Px = conc of x in plasma
 Measurement of GFR
• Creatinine is also used for GFR
– partially reabsorbed, particularly in uremia
• then clearance < GFR

• Some substances are filtered, enter tubules &

more of the substance is secreted
– Enters tubules
– Clearance > GFR

• Some substances are filtered, enter tubules,

but are completely reabsorbed,
– Do not reach final urine
– Eg cystatin C
 Plasma Creatinine

• 1-2% of muscle creatine spontaneously

converts to creatinine daily
• Endogenous creatinine produced is
proportional to muscle mass
– Function of total muscle mass
• production varies with body mass, age & sex
 Plasma Creatinine

• Dietary fluctuations of creatinine intake cause

only minor variation in daily creatinine
excretion of same person
– Creatinine released into body fluids at a constant
rate
– Plasma levels maintained within narrow limits
• Creatinine clearance may be measured as
an indicator of GFR
 Plasma Creatinine

• Small quantity of creatinine is reabsorbed by

tubules & other quantities are actively
secreted by renal tubules
• Creatinine clearance is approximately 7%
greater than inulin clearance
– Difference is not significant when GFR is normal
– Normally about of 120 ml/min in adults
 Plasma Creatinine
When GFR is low, < 10 ml/min
• Tubular secretion makes major contribution to
creatinine excretion
• Creatinine clearance significantly
overestimates GFR
 Plasma Creatinine
• Estimate of GFR can be calculated from creatinine
content of a 24-hour urine collection & plasma conc
within this period
• Volume of urine is measured, urine flow rate is
calculated (ml/min) & assay for creatinine is
performed on plasma & urine to obtain conc in
mg/dl or mg/ml
 Plasma Creatinine

Actual GFR Using Creatinine

• Creatinine levels vary during the day
– For V & U to be accurate, urine needs to be
collected over 24 hr
– Makes test time-consuming
• Estimated GFR uses only plasma creatinine
– Used to identify patients needing actual GFR
 Plasma Creatine
Prediction of Creatinine Clearance (CC) from
plasma creatinine
• Cockcroft & Gault Formula
CC = k[(140-Age) x weight(Kg))]
serum creatinine (µmol/L)
– Where k = 1.224 for males & 1.04 for females
– Modifications required for children & obese
subjects
– Can be modified to use surface area
 Plasma Urea

• Urea = major N-containing metabolic product

of protein catabolism in humans
• >90% of urea excreted through kidneys,
• Losses through GIT & skin
• Urea is filtered freely by glomeruli
 Plasma Urea

• Plasma urea conc often used index of renal

glomerular function
– Blood urea nitrogen (BUN)
• Urea production increased by high protein
intake
• Decreased in patients with a low protein intake
• In patients with liver disease
• Non-specific test
 Plasma Urea
• Reference interval for serum urea of healthy
adults is 5-39 mg/dl
– Slightly higher in males than females.
• Non-renal factors can affect urea level
– Mild dehydration
– High protein diet
– Increased protein catabolism
– Muscle wasting as in starvation
– Reabsorption of blood proteins after a GIT
haemorrhage
– Treatment with cortisol or analogues
 Uric Acid

• Major product of catabolism of purine

nucleosides, adenosine & guanosine
• Purines are derived from:
• catabolism of dietary nucleated cells, like meat
• degradation of endogenous nucleic acids
 Uric Acid
• Overproduction of uric acid may result from
increased synthesis of purine precursors
• Approximately 75% of uric acid excreted is
lost in urine
• Rest mainly secreted into GIT
• Hyperuricemia = serum or plasma uric acid
concentrations:
– > 7.0 mg/dl or 0.42mmol/L in men
– > 6.0 mg/dl or 0.36mmol/L in women
 Plasma β2-microglobulin

• β2-microglobulin = small peptide MW 11.8

kDa
• Present on surface of most cells & in low conc
in plasma
 Plasma β2-microglobulin

• Good index of GFR in normal people

• Unaffected by diet or muscle mass
• Increased in certain malignancies & inflammatory
diseases
• Completely filtered by glomeruli & is
reabsorbed & catabolized by proximal tubular
cells
• Measurement of excretion is sensitive method of
assessing tubular integrity
 Acute Renal Failure

Metabolic features:
• Retention of:
– Urea & creatinine
– Na & water
– potassium with hyper-kalaemia
– Acid with metabolic acidosis
 Acute Renal Failure
Classification of Causes:
• Pre-renal
– reduced perfusion
• Renal
– inflammation
– infiltration
– toxicity
• Post-renal
– obstruction