RENAL FUNCTION TESTS

ANATOMY
 RENAL FUNCTIONS
1. Excretion of metabolic waste products
2. Retention of substance vital to body
3. Hormonal function
a. Erythropoietin
b. Calcitriol
c. Renin
4. Maintenance of homeostasis
 GLOMERULAR FUNCTION

• Glomerular filtration rate (GFR) checks the renal

excretory function.

• Definition: GFR is the volume of fluid filtered from

the renal glomerular capillaries into the Bowman's
capsule per unit time.

Normal GFR = 120 ±25 mL/min/1.73 m2

Note: Normal range depends on the size of an individual, and should be corrected
for surface area-typically 1.73 m2
TUBULAR FUNCTION
• Tubular epithelial cells are
highly specialized tissue –
able to selectively reabsorb
some substances and secrete
others.
• 170 L/day------filtered
• 1.5 L/day ------excreted
• Nearly 99 % water
reabsorbed substance Threshold value

• Renal threshold – plasma glucose 180 mg/dL

lactate 60 mg/dL
level above which compound bicarbonate 28 mEq/L
is excreted in urine calcium 10 mg/dL
RENAL FUNCTION TESTS
- Glomerular filtration tests
1) Inulin clearance
2) Creatinine clearance
3) Urea clearance

4) Serum Creatinine
5) BUN
6) Serum uric acid level
 GLOMERULAR FUNCTION
- GFR measures excretory function of the kidneys.
- Glomerular filtration rate is given by the
formula:

To calculate GFR, we need to calculate or measure the

concentration of any chemical present within the body
(eg.creatinine) or
inject such a chemical into the body (eg.Inulin) which is not
harmful to the body and is neither reabsorbed nor secreted
by the kidneys.
Substance Filtered Reabsorbed Secreted Amount excreted

/minute in
relation to amount
filtered
GLUCOSE YES YES, NO Not excreted
completely normally

UREA YES YES NO Less

CREATININE YES NO NO Very close

PAH (Para- YES NO YES More than that

aminohippurate filtered
)
YES NO NO GFR = Clearance
INULIN,
MANNITOL,
Thiosulphate
 CALCULATING GFR USING INULIN

• In this method, INULIN is injected into the plasma.

INULIN is neither secreted nor reabsorbed by the
kidneys.
• Therefore the rate of excretion of inulin is directly
proportional to the rate of filtration of solutes from
the glomerular capillaries.

• But, the process is cumbersome & not practically

applicable.
 INULIN CLEARANCE TEST
10 gm INULIN in
Light 100 ml saline
Overnight
breakfast at injected i.v. at
fast
7:30 am
10 ml/min at 8am

Bladder After 30 After 60

emptied at mins, urine mins, urine
9am, urine and blood and blood
discarded collected collected

INULIN = Ideal substance

Using ‘Solute Clearance’ to estimate GFR
Renal clearance of a solute is the amount of blood the
kidneys can make a free of specific solute in each minute.
Definition of CLEARANCE
The volume of plasma completely cleared of
a given solute per unit time.

Eg.
Formula for using inulin clearance in calculation of
GFR is:

Clearance = urine inulin concentration x volume

(ml)
 INULIN CLEARANCE TEST
Light 10 gm INULIN in 100 ml
Overnight breakfast at saline injected i.v. at
fast 7:30 am 10 ml/min at 8am

Bladder
After 30 mins, After 60 mins,
emptied at
urine and blood urine and blood
9am, urine
collected collected
discarded

Normal INULIN Clearance= 125 ml/min /1.73 m2 BSA

[range = 100 to 150 ml/min]

 Calculating GFR using CREATININE CLEARANCE
(CrCl)

• Creatinine is a waste of normal muscle metabolism.

• Measuring the creatinine clearance is easier than
measuring inulin as creatinine is readily available in
the body.

• The kidneys filter creatinine from the blood into

the urine, and reabsorb almost none of it.
• Considering the muscle mass remains stable,
creatinine clearance can give a good idea of GFR.
 CREATININE CLEARANCE (CrCl)
Definition of Creatinine Clearance
The volume of plasma completely cleared of
a creatinine per unit time.

Formula for using creatinine clearance in calculation

of GFR is:

CrCl = urine creatinine concentration x volume (ml)

plasma creatinine concentration x time (min)
 METHODOLOGY
• Amount of creatinine present in a sample of
urine collected over 24 hours is measured.
• This method requires a person to urinate
exclusively in a plastic jug for one day, then
bring it in for testing.

Creatinine clearance in healthy person is 125mL/min.

• Normal range: Male = 97 to 137 ml/min.
Female = 88 to 128 ml/min
( note: GFR can vary depending on age, sex, and size)
 Corrected Creatinine Clearance for estimating GFR
• Ccr-corrected = Ccr × 1.73 / BSA

Using this formula,

Normal GFR = 120 ± 25 mL/min/1.73 m2

Advantage: Disadvantage:
-CrCl is generally a good -inconvenient
indicator of GFR. -error in urine
collection
( unreliable results)
 Endogenous Creatinine Clearance Test
Abnormal results (lower values) may indicate:

• Glomerular injury ( Eg. Infection, inflammation,

trauma)
• Damage to the tubular cells
• Decreased renal perfusion (eg. shock, dehydration)
• Loss of body fluids (eg. vomiting, dehydration, burns)
• Bladder outlet obstruction
• Renal failure
 UREA clearance test
Urea is a waste product that is created by protein
metabolism and excreted in the urine.

Normal reference range = 10 to 36 grams/24 hours.

(urea clearance)

Abnormal results (low clearance values) may

indicate decreased ability of the kidneys to excrete
urea.
Disease Urea clearance
Nephrotic Normal until onset of renal
syndrome insufficiency

Benign Normal clearance usually maintained

hypertension indefinitely

Chronic Falls progressively

nephritis Reaches value of half or less of normal
before blood urea concentration
begins to rise
Terminal About 5 % of normal
uremia
 Agents used Clearance tests
• Gold standard = INULIN
• Silver standard – Cr51 - EDTA
Tc99 - DTPA
I125 – iothalamate
iohexol
• Bronze standard – creatinine
cystatin C
• Minimal clinical use – urea clearance
α1 – microglobulin
 Grading of kidney disease based on GFR
state grade GFR ml/min/1.73sq m
Minimal damage 1 >90
Mild damage 2 60 – 89
Moderate 3 30 – 59
damage
Severe damage 4 15 – 29
End stage 5 < 15

Chronic Kidney Disease = GFR < 60 ml/min/1.73 m2

for 3 months or more
RENAL FUNCTION TESTS
- Glomerular filtration tests
1) Inulin clearance
2) Creatinine clearance
3) Urea clearance

4) Serum Creatinine
Blood plasma
5) BUN
tests
6) Serum uric acid level
 Estimating GFR from plasma measurements

• GFR can be estimated using a

single blood test to check serum
creatinine level.
Different formulae are
available to estimate GFR
based on serum creatinine
level.
Normal = 0.7 – 1.36 mg/dL
Increasing values indicate decreasing GFR.
 Estimated GFR ( eGFR)
The Cockcroft and Gault equation:

CrCl = (140 –age) x lean body weightx1.22 for M or 1.04 for F

serum creatinine (micromol/L)

The Cockcroft and Gault equation is reasonably accurate at

normal to moderately impaired renal function

Note: To convert creatinine in mg/dl to μmol/l, multiply by 88.4

MODIFICATION OF DIET IN RENAL DISEASE
(MDRD) study equation
 Normal Serum Creatinine= 0.7 – 1.36 mg/dL
Decrease Increase
Low muscle mass Old age
Malnutrition Glomerulonephritis; Pyelonephritis
Females Urinary obstruction
Dehydration, shock
Renal failure
Drugs
- Diuretics
- NSAIDs
- Chemotherapy medications
- Antibiotics eg. Amphotercin B,
Gentamicin, Vancomycin
- Cyclosporin A ( used after organ transplant)
 BLOOD UREA NITROGEN (BUN)

• Urea is a relatively nontoxic substance made by the

liver to dispose of ammonia resulting from protein
metabolism.

• Normal BUN range = 15- 40 mg/dL

-The real urea concentration is BUN x 2.14

• BUN is a sensitive indicator of renal disease

UREA:
• Protein and amino acid catabolism ( liver)  urea 
easily diffusible to all body compartments

• freely filtered at the glomeruli  reabsorbed by the

proximal and distal tubules

• BUN concentration is primarily regulated by renal

tubular reabsorption, which is highly dependent on
urine flow rate.
 Increased BUN is known as Azotemia
Causes of Azotemia:
- any cause of volume depletion ( dehydration,
hemorrhage, congestive cardiac failure, shock etc)
- Increased protein diet
- Hyperalimentation (total parenteral nutrition)
- Upper GI bleeding (BUN/ Creatinine > 20:1)
- Rhabdomyolysis (BUN/ Creatinine ratio decreases)

Causes of decreased BUN

-Any cause of blood volume expansion
- Malnutrition
- Liver failure Normal BUN/Crea ratio = 10: 1
Causes of Azotemia
• Pre renal
azotemia

• Renal
azotemia

• Post renal
azotemia
 Increase in blood urea nitrogen
Pre - renal Renal Post renal Drugs
Dehydration Glomerulo- Renal ACEI
Severe vomiting nephritis calculi
Diarrhea Acetaminophen
Intestinal Malignant Enlarged
obstruction hypertension prostate Aminoglycosides
Diabetic coma
Severe burns Chronic Tumors of Amphotericin B
(all of above cause pyelonephritis bladder
volume depletion) Diuretics
Fever, UGI bleeding ATN
Severe infections NSAIDS
(↑protein catabolism) Renal failure
Rhabdomyolysis Sulfonamides
Drugs Chemotherapy

Decreased blood urea – late pregnancy, starvation, hepatic failure

Serum concentration increases as age advances
Serum Uric Acid
 Uric acid is the major product of the catabolism of the
purine nucleosides (adenosine and guanosine)

 Purines are derived from catabolism of dietary nucleic

acid & from degradation of endogenous nucleic acids.

 Overproduction of uric acid may result from increased

synthesis of purine precursors.

 Approximately 75% of uric acid excreted is lost in the

urine; most of the reminder is secreted into the GIT.
 Renal handling of uric
acid is complex and
involves 4 steps:
-Glomeruli filters almost
all uric acid into tubules.
-Proximal convoluted
tubule reabsorb 98 to
100% of filtered uric acid

-Subsequent secretion of
uric acid into the lumen
of distal portion of the
Hyperuricemia is defined by serum
proximal tubules.
or plasma uric acid concentrations :
-Further reabsorption in
> 7.0 mg/dL in men
the distal tubule.
> 6.0 mg/dLin women
RENAL FUNCTION TESTS

- Glomerular filtration tests

1) Inulin clearance
2)Creatinine clearance
3)Urea clearance
4) Serum Creatinine
5) BUN Blood plasma
6) Serum uric acid level tests

-Glomerular permeability test

 Test for glomerular permeability
• Increase in glomerular permeabilty can be the first
sign of glomerular injury (even before decrease in GFR)
• This is often seen as proteinuria
• Normal protein excretion = <150 mg/24 hrs
• Glomerular • Tubular • Overflow
proteinuria proteinuria proteinuria

Glomerular Decrease in
reabsorptive Increased amounts of
damage capacity of tubules Increase in low molecular
low molecular
weight proteinsweight
Eg. Eg. Beta2 proteins in urine
albuminuria microglobulin Eg. Bence jone
proteinuria in myeloma
GLOMERULAR PROTEINURIA
Albuminuria ( early morning urine sample preferred)
< 300 mg/day Benign proteinuria; but may
be an early sign of renal
damage in DM, Hypertension
300 – 1000 mg/day Pathological proteinuria

> 2 gram/day Glomerular cause likely

Albuminuria > 3.5gram/day Nephrotic syndrome

Small quantity of albumin Acute nephritis, pregnancy

Measurement of albuminuria is also helpful in monitoring kidney

function & response to therapy in CKD
 RENAL FUNCTION TESTS

3) Tests to evaluate Tubular function

- urine concentrating ability
-urine acidifying ability
- Na handling ability
 Concentration tests ( aka Fluid deprivation tests)
Ability of kidney to concentrate urine is
determined by measuring of specific gravity of
urine.
• Most sensitive means of detecting early
impairment in renal function

• Specific gravity of urine measures the

concentration of the excreted molecules in urine
( i.e. the urine osmolarity)
Normal Range = 1.001 to 1.030
 Tests Of Urinary Acidification
• Renal acidification mechanism are usually examined
in children with suspected renal tubular acidosis.

• Urine pH : pH of a fresh urine sample is tested with

pH meter.
• A concentrated, fasting, morning sample of urine is
acidic.
• A pH of <5.5 virtually excludes distal renal tubular
acidosis.