Renal Function Tests (RFT) - I

Specific learning objectives

By the end of this lecture, you should

• List the functions of kidney

• Classify renal function tests

• What are the markers of renal function in blood?

• Define glomerular filtration rate (GFR) & clearance

– How is it measured?
– Importance
 Nephron - functional unit of the kidney

~ 1 milion nephrons per kidney

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 Excretion of waste products

• Glomerular function
– Ultrafiltration of blood

• Tubular function
– Reabsorption
– Secretion

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 Functions of kidney
• Excretes metabolic waste products, drugs and toxins

 Regulates water and electrolyte balance

 Regulates body acid-base balance
 Endocrine function
Synthesis and secretion of
– Vitamin D (1,25 dihydroxy cholecalciferol)
– Renin
– Erythropoitein
 Renal Function Tests (RFT)
• A group of laboratory investigations done to aid in the
diagnosis and monitoring of renal disorders

A. Routine tests
B. Glomerular function test
C. Tubular function test
 Renal Function Tests (RFT)
A. Routine clinical tests (screening tests):
1. Measurement of markers of kidney function in blood
– urea and creatinine
2. Complete urine analysis
3. Measurement of serum electrolytes

B. Tests to assess glomerular function:

1. Clearance tests – to measure glomerular filtration rate (GFR)

C. Tests to assess tubular function:

1. Measurement of urine and plasma osmolality
2. Tests to assess ability of the renal tubule to concentrate and dilute
urine.
3. Tests to access renal acidification
4. Tests to access renal handling of sodium
 Renal Function Tests (RFT)
A. Routine clinical tests (screening tests):
1. Measurement of markers of kidney function in blood
– urea and creatinine
2. Complete urine analysis
3. Measurement of serum electrolytes

B. Tests to assess glomerular function:

1. Clearance tests – to measure glomerular filtration rate (GFR)

C. Tests to assess tubular function:

1. Measurement of urine and plasma osmolality
2. Tests to assess ability of the renal tubule to concentrate and dilute
urine.
3. Tests to access renal acidification
4. Tests to access renal handling of sodium
Measurement of markers of renal function in blood

• Urea, creatinine, uric acid are the major non-protein

nitrogenous substances (NPN) present in blood

• Removed from circulation by the kidneys in urine

• Blood levels of these compounds are elevated

in renal failure

• Serum urea and creatinine are markers of renal function

 1. Urea
• Waste product derived from amino acid catabolism

• Synthesized in liver : urea cycle

• Excreted by the kidneys

Serum urea levels: 15-40 mg/dL

High levels seen in renal failure

• Elevated levels can be seen in some conditions, when
renal function is normal

Levels of urea depend on:

• Rate of synthesis
– Protein content of diet
– Protein catabolism (starvation, tissue damage, sepsis)
– Liver function

• Rate of excretion
– Renal function
– Renal perfusion (renal blood flow)
 Increased serum urea levels

Pre-renal Renal Post-renal

•Decreased renal perfusion •Acute renal failure •Stones

− dehydratio •Chronic renal failure •Strictures
− sho k •Tumors
− heart failure

•Increased breakdown of proteins

− starvatio
− prolo ged ill esses
− high protei diet
 Creatinine
• Creatine phosphate in skeletal muscle is metabolised to
creatinine

• Conversion of creatine to creatinine is

– Spontaneous and non-enzymatic
– Happens at a constant rate
– Not affected by diet, age

• Creatinine is excreted by the kidneys

• As long as kidney function is normal, the blood levels of

creatinine is constant (unlike urea)
 Serum creatinine
– Male : 0.6 – 1.2 mg/dL
– Female : 0.5 – 0.9 mg/dL

• High levels of creatinine is most commonly associated

with renal failure

• Therefore, serum creatinine levels is a more specific

marker of renal function than blood urea levels
 Renal Function Tests (RFT)
A. Routine clinical tests (screening tests):
1. Measurement of markers of kidney function in blood
– urea and creatinine
2. Complete urine analysis
3. Measurement of serum electrolytes

B. Tests to assess glomerular function:

1. Clearance tests – to measure glomerular filtration rate (GFR)

C. Tests to assess tubular function:

1. Measurement of urine and plasma osmolality
2. Tests to assess ability of the renal tubule to concentrate and dilute
urine.
3. Tests to access renal acidification
4. Tests to access renal handling of sodium
 Glomerular function

Glomerular filtration rate (GFR)

• The volume of plasma
that is filtered
across the glomerular membrane
per unit time

• 120mL/min
• Estimation of GFR is the best overall measure of kidney
function

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Why is it important to measure GFR, while
serum markers of renal function (urea and
creatinine) are available?
• Therefore, serum creatinine is not a sensitive marker of
renal function

• Cannot detect early stages of renal failure

• It is important to measure GFR to detect early stages of

renal failure
 How to measure GFR?
Clearance:
It is defined as
the volume of plasma
from which a substance is
completely removed
by the kidney in one minute
Calculation of clearance

Amount filtered = Amount excreted

PCr X GFR = UCr X Volume of urine /min
 Calculation of clearance

Clearance = U X V
P
U: concentration of substance in urine
P: concentration of substance in plasma
V: Volume of urine produced per minute (ml/min)

A 24 hour urine sample is often required

Volume of urine per min = Volume of 24 hr sample
24 X 60
 Clearance = GFR
Ideal characteristics of a substance used to measure GFR:

 Must be excreted mainly by the kidney

 Must have constant blood level
 Must be freely filtered at the glomerulus
 Must NOT be secreted OR reabsorbed by the renal tubule

 Should be easy to measure in the lab

 If an exogenous substance used, it should be non-toxic
• Clearance of a substance is equal to the GFR if it is
neither secreted nor reabsorbed by the renal tubule

• Clearance of a substance is less than the GFR if it is

reabsorbed by the renal tubule

• Clearance of a substance is more than the GFR if it is

secreted by the renal tubule
 Inulin clearance

Gold standard for measuring GFR

Inulin is a polysaccharide of fructose

It meets all the essential criteria for measurement of GFR

Disadvantages:
1. It has to be injected intravenously at a constant rate
2. Measurement in the laboratory is difficult
 Creatinine clearance
• Creatinine is the substance most commonly used to
measure GFR
• It meets almost all the criteria
 It is excreted mainly by the kidney
 It has a constant blood level
 It is freely filtered at the glomerulus
 It is secreted to a small but variable extent by the renal
tubules

 It is easily easured i the la oratory Jaffe’s rea tio

 It is produced in the body (endogenous)
 Creatinine clearance

• Male: 105 ± 20 mL/min

• Female: 95 ± 20 mL/min
The difficulty in measurement of creatinine clearance
is mainly in obtaining an accurate 24-hour urine sample

Clearance = U X V
P
 Estimated GFR (eGFR)
GFR can also be estimated directly from serum creatinine
(without having to measure urine creatinine)
by the use of formulae such as:

1. Cockcroft - Gault formula

2. MDRD equation
 Cockcroft – Gault formula

eGFR = (140 – age) (weight in kg) (0.85 if female)/ 72 × serum creatinine

Modification of diet in renal disease (MDRD)

eGFR = 175 x serum creatinine –1.154 x age –0.203 x (0.742 if female) x (1.210 if black)
 Uses of GFR

• Estimate of renal function

• Classification of stages of chronic kidney disease
• Titration of drug dosage in patients with renal failure
 Cystatin C
• Substance to measure GFR
• Protein – produced by all cells

– Endogenous production
– Completely filtered
– Reabsorbed and metabolised by PCT
– Not secreted

• Levels do not vary with race, age, sex, muscle mass

• Levels rise early in renal failure

• High cost, not routinely available lab test

 Specific learning objectives
• List the functions of kidney
• Classify renal function tests
– routine, glomerular, tubular

• What are the markers of renal function in blood?

– Serum urea and creatinine

• Glomerular filtration rate & clearance

– Ideal characters of substance to measure GFR

– Creatinine clearance
– Inulin clearance is the gold standard method to measure GFR
– Cystatin C
– Uses of GFR estimation
 References
• Clinical Chemistry: Principles, Procedures, Correlations, 6th
edition,2010. Michael L. Bishop, Edward P. Fody, and Larry
Schoeff. (Chapter – 26 Renal function) Page no: 564-565