Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Renal Function Test Lecture PPT
RENAL FUNCTION TEST
DR. S. SHEKHAR
ASSOC. PROFESSOR
DEPT. OF BIOCHEMISTRY
FUNCTIONS OF KIDNEY
1. Maintenance of homeostasis:
The kidneys are responsible for the regulation of water,
electrolyte & acid-base balance in the body.
2. Excretion of metabolic waste products:
The end products of protein & nucleic acid metabolism
are eliminated from the body. These include urea,
creatinine, creatine, uric acid, sulfate & phosphate
3. Retention of substances vital to body:
The kidneys reabsorb & retain several substances of
biochemical importance in the body e.g. glucose,
amino acids etc
4. Hormonal functions:
A. Erythropoietin:
A peptide hormone, stimulates haemoglobin synthesis
and formation of erythrocytes.
B. 1,25-Dihydroxycholecalciferol (calcitriol):
The active form of vitamin D is finally produced in the
kidney. It regulates calcium absorption from the gut.
C. Renin:
A proteolytic enzyme liberated by kidney, stimulates
the formation of angiotensin II which, in turn, leads to
aldosterone production.
Angiotensin II & aldosterone hormones involved in
the regulation of electrolyte balance.
URINE FORMATION
? Nephron is the functional unit of kidney.
? Each kidney is composed of approximately one million
nephrons.
? Nephron, consists of a Bowman's capsule (with blood
capillaries), proximal convoluted tubule (PCT), loop of
Henle, distal convoluted tubule (DCT) & collecting
tubule.
? About 1200 ml of blood (650 ml plasma) passes through
the kidneys, every minute.
? About 120-125 ml is filtered per minute by the
kidneys & this is referred to as glomerular filtration
rate (GFR).
? With a normal GFR (120-125 ml/min), the glomerular
filtrate formed in an adult is about 175-180 litres/day,
out of which only 1.5 litres is excreted as urine.
? More than 99% of the glomerular filtrate is
reabsorbed by the kidneys.
? Urine formation basically involves two steps
glomerular filtration & tubular reabsorption.
Glomerular filtration
? This is a passive process that results in the
formation of ultra filtrate of blood.
? All the (unbound) constituents of plasma, with a
molecular weight < 68,000, are passed into the
filtrate.
? The glomerular filtrate is almost similar in
composition to plasma except proteins and cell.
Tubular reabsorption
? The renal tubules (PCT, DCT & collecting
tubules) retain water & most of the soluble
constituents of the glomerular filtrate by
reabsorption.
? This may occur either by passive or active
process.
Renal threshold
? There are certain substances in the blood whose
excretion in urine is dependent on their concentration.
? Such substances are referred to as threshold substances.
? At the normal concentration in the blood, they are
completely reabsorbed by the kidneys.
? But when their blood levels are elevated beyond the
normal range exceeding the tubular reabsorption capacity
the excesss is excreted in urine.
? The renal threshold of a substance is defined as its
concentration in blood (or plasma) beyond which it is
excreted into urine.
v
The renal threshold for
Glucose --------180 mg/dl
Ketone bodies--- -3 mg/dl
Calcium ----------10 mg/dl
Bicarbonate ------ 30 mEq/l
vTubular maximum (Tm):
? The maximum reabsorptive capacity of the
renal tubules to absorb a particular substance.
? Tubular maximum for glucose is 375 mg/min
INDICATION
1. Detection of renal damage
2. Assessment of extent of renal damage
3. Monitoring the progression of renal damage /
disease
4. Monitoring and adjusting the dose of
potentially renal toxic drugs
5. Before giving renal excretory contrast in some
diagnostic procedure
CLASSIFICATION
I. GLOMERULAR FILTRATION CAPACITY TEST
I. Clearance tests
II. Serum urea
III. Serum creatinine
II. GLOMERULAR
FILTRATION
BARRIER
INTEGRITY TEST
A. Proteinuria
B. Hematuria
C. Urine protein electrophoresis
III. TUBULAR FUNCTION TESTS
A. Reabsorption test
B. Renal concentration test/ water deprivation test
C. Osmolality
D. Specific Gravity
E. Urine dilution test
F. Sodium Excretion Test
G.Ammonium Chloride loading test or urinary
acidification test
IV. COMPLETE URINE ANALYSIS
I. GLOMERULAR FILTRATION CAPACITY TEST
? It measures the total filtration occuring at glomerulus.
? These indicates the percentage, or fraction of the total
nephron that are functioning.
A decrease in 50% filtration capacity
indicates that about half of the total nephrons have
lost their function.
1. RENAL CLEARANCE TESTS
? To assess the rate of glomerular filtration & renal
blood flow.
? "The renal clearance of a substance is defined as the
volume of plasma from which the substance is
completely cleared by the kidneys per minute."
? This depend on
- plasma conc. of the substance & it's
excretary rate
- GFR
- Renal plasma flow
Renal Clearance Tests
? The GFR (Normal = 120 ml/minute )
? Usually equal to clearance of that substance and is
calculated by the following equation
U x V
C =
P
Where, C = Clearance of the substance (ml/mt)
U = Conc.of substance in urine (mg/L)
P = Conc.of substance in plasma (mg/L)
V = Vol.of the urine passed per minute
Renal metabolic
Clearance Value
Example
change
Vs GFR
Substance only
Clearance = GFR
Inulin
filtered
( No reabsorbtion
No secretion)
Substance filtered
Clearance < GFR
Urea
and reabsorbed
Substance filtered
Clearance > GFR
Creatinine
and secreted
A. Urea clearance test
? Urea is the end product of protein metabolism.
? After filtered by the glomeruli, it is partially
reabsorbed by the renal tubules.
? So, Urea clearance is less than the GFR & it is
influenced by the protein content of the diet.
? Urea clearance is not as sensitive as creatinine
clearance.
Urea clearance test
? Urea clearance is defined as the volume (ml) of plasma
that would be completely cleared of urea per minute.
? If the output of urine is more than 2 ml per minute.
[ V > 2ml/min]
This is referred to as maximum urea clearance & the
normal value is around 75 ml/min
? It is calculated by the formula:
U X V
Cm =
P
? Cm=Maximum urea clearance.
? U = Urea concentration in urine (mg/dl).
? V = Urine excreted per minute in ml.
? P = Urea concentration in plasma.
Standard urea clearance
? The urea clearance drastically changes when the
volume of urine is less than 2 ml/min.
[ V < 2ml/min]
? This is known as standard urea clearance (C) & the
normal value is around 54 ml/min
? Standard urea clearance is calculated by a modified
formula
U X V
Cs =
P
? A urea clearance value below 75 % of the normal
indicates renal damage.
? Usually blood urea level start rising only when
the clearance value falls below 50% of the
normal.
? Urea clearance values may not always coincide
with blood urea level.
? Urea is reabsorbed by the renal tubule and
hence tubular function affects urea clearance.
? Normal level of blood urea: 20-40 mg/dl
B. Creatinine clearance test
? Creatinine is an excretory product derived from
creatine phosphate in muscle.
? The excretion of creatinine is rather constant &
is not influenced by body metabolism or
dietary factors.
? Creatinine is filtered by the glomeruli & only
marginally secreted by the tubules.
? Creatinine clearance may be defined as the
volume (ml) of plasma that would be
completely cleared of creatinine per minute.
Procedure:
? In the traditional method, creatinine content of a 24 hr
urine collection & the plasma concentration in this
period are estimated.
? The creatinine clearance (C) can be calculated as
follows:
U X V
Ccr = P
U = Urine concentration of creatinine.
V = Urine output in ml/min (24 hr urine volume
divided by 24 x 60)
P = Concentration of creatinine.
? The normal range of creatinine clearance is
around 120-145 ml/min.
? A decrease in creatinine clearance ( <75% of
normal ) indicate a decrease GFR reflecting
renal damage.
? It is helpful in the early detection of functional
impairment of kidney and also for monitoring
the patients with renal insufficiency
? In older people, the clearance is decreased.
Creatinine clearance test as a GFR marker
Advantages
Disdvantages
1. It is not affected by diet or 1. Secreted by tubule, so
exercise
clearance > GFR
2. Extrarenal factors will rarely
interfere.
2. Overestimate GFR by
10-20 ml/min
3. Conversion of creatine
phosphate to creatinine is 3. Very early stages of
spontaneous, non-enzymatic.
decrease in GFR (50-70
4. As the production is
ml/min) may not be
continuous, the blood level
identified by creatinine
will not fluctuate. Blood
clearance (creatinine
may be collected at any time.
blind area).
Relation between GFR AND Plasma Creatinine
C. Inulin Clearance Test
? Method of choice when accurate determination
of GFR is required.
? Inulin is polysacharide of Fructose.
? Freely filtered by glomerulus not reabsorbed not
secreted or metabolically altered by the renal
tubule.
? Normal value : 120 ml/mt.
? Disadvantages :need for its
IV adminstration
technically difficulty of
analysis
D. Cystatin C as a filtration marker
? It is a LMW nonglycosylated protein produced at a
constant rate by all nucleated cells in the body,
? Freely filtered by the glomeruli, and totally reabsorbed
by the renal tubules.
? It is not secreted, by the tubules. Thus, its plasma level is
determined by GFR.
? Normal adults have circulating level of approx. 1mg/l.
? This is better indicator of renal function as compared to
creatinine in early stages of GFR impairment as it is
independent of age,gender,body composition & muscle
mass.
E. Estimated GFR (eGFR)
? A simpler technique of estimating creatinine
clearance and there by GFR is by using serum
creatinine level.
? This would eliminate the need for timed urine
collections.
? A commonly used formula is Cockcroft-Gault
equation.
? Ccr = (140 ? age in years) ? weight in Kg (0.85 in
females)/72 ? Pcr in mg/dL
? The factor 0.85 is used in females assuming that they
have 15% less muscle mass.
MDRD (Modification of Diet in Renal Disease) Formula
? This equation directly estimates GFR.
? The estimated GFR (eGFR) (mL/min/1.73m2)
eGFR = 186 ? (Creatinine/88.4) -1.154 ? (Age) ?0.203 ?
0.742 (if female)
? Estimates GFR adjusted for body surface area.
? Designed for use with laboratory creatinine test.
? Is more accurate than creatinine clearance measured from
24-hour urine collections or estimated by the Cockcroft-
Gault formula.
GRADING OF CHRONIC KIDNEY DISEASE
2. Serum urea
? Urea is major nitrogenous end product of protein and
amino acid catabolism, produced by liver and distributed
throughout intracellular and extracellular fluid.
? Urea is freely filtered by the glomeruli
? 40-70% of it is passively absorbed by diffusion into
renal tubules depending upon urine flow rate.
? The reference interval - 10-40 mg/dl
? High protein diet causes significant increases in plasma
urea concentrations
? Many renal diseases with
various glomerular, tubular,
interstitial or vascular damage can cause an increase
in plasma urea concentration
? Nonrenal factors can affect the urea level
a) Mild dehydration,
b) high protein diet,
c) increased protein catabolism,
d) muscle wasting as in starvation,
e) reabsorption of blood proteins after a GIT
haemorrhage,
f) treatment with cortisol or its synthetic
analogous
? States associated with
elevated levels of urea in blood are
referred to as uremia or azotemia
? Causes of plasma urea elevations:
Prerenal: renal hypoperfusion
Renal: acute tubular necrosis
Postrenal: obstruction of urinary flow
? Parallel determination of urea and creatinine is
performed to differentiate between pre-renal and post-
renal azotemia
? Pre-renal azotemia leads to increased urea levels, while
creatinine values remain within the reference range.
? In post-renal azotemias both urea and creatinine levels
rise, but creatinine in a smaller extent
BLOOD UREA NITROGEN (BUN)
? Sometimes, blood urea level is expressed as blood urea
nitrogen (BUN)
? BUN is the nitrogen content of urea present in blood
? Molecular weight of urea is 60 in which the
contribution of nitrogen atoms is 28
? Therefore, BUN equals blood urea multiplied by 28/60
i.e. nearly 0.47
? The normal range of BUN is 10-20 mg/dl
? A rise in nitrogen content of blood is called azotaemia
Serum creatinine
? Creatinine is a breakdown product of creatine
phosphate in muscle, and is usually produced at a
fairly constant rate by the body depending on muscle
mass
? Creatinine is filtered but not reabsorbed in kidney.
? A small amount of creatinine is secreted into tubules
and its secretion is increased with the increasing level
of plasma creatinine.
? Normal range is 0.8-1.3 mg/dl in men and 0.6-1 mg/dl
in women
? Not increased above normal until GFR<50 ml/min .
Increased serum creatinine
? Impaired renal function
vDrugs:
? Anabolic steroid users
? Probenecid
? Vary large muscle mass:
? Cimetidine
body builders,
? Triamterene
acromegaly patients
? Trimethoprim
? Rhabdomyolysis/crush
? Amiloride
injury
? Athletes taking oral
creatine
Determination of serum creatinine gives a useful
indication of the degree of renal failure
II. GLOMERULAR FILTRATION BARRIER
INTEGRITY TEST
Glomerulus acts as a selective filter of the blood passing
through its capillaries
A. PROTEINURIA
? Proteinuria is the first sign of glomerular injury
before any decrease in GFR.
? The glomeruli of kidney are not permeable to
substances with molecular weight more than 69,000
& plasma proteins are absent in normal urine
PROTEINURIA
? When glomeruli are damaged or diseased, they become
more permeable & plasma proteins may appear in urine.
? The smaller molecules of albumin pass through damaged
glomeruli more readily.
? Albuminuria is always pathological
If total protein excretion > 150 mg/day
Or
Albumin excretion > 30 mg/day
Indicative of glomerular damage
MICRO-ALBUMINURIA
? It
is
also
called
minimal
albuminuria
or
paucialbuminuria.
? It is an early indicator of onset of nephropathy due to
microvascular glomerular damage.
? Micro albuminuria is an early indication of nephropathy
in patients with diabetes mellitus & hypertension.
? It is identified, when small quantity of albumin (30-300
mg/day) is seen in urine.
? It is also expressed as albumin creatinine ratio. Albumin
creatinine ratio ? 30-300mg albumin /gm of creatinine
URINARY PROTEIN ELECTROPHORESIS
? Urine protein electrophoresis separates the proteins
according to charge and allows classification of the type
of renal injury.
? Protein patterns are interpreted and classified as
glomerular, tubular, or mixed patterns
In minimal glomerular damage
Low molecular weight protein such as albumin,
1- AT, and transferrin are excreted
In severe glomerular damage
other proteins having high molecular weight
like immunoglobulin are excreted into urine
TUBULAR PROTEINURIA occurs when the renal tubules
cannot reabsorb low molecular weight proteins
Tubular
proteinuria
is ? This
protein
pattern
associated with
reveals protein bands in
? Drug toxicity
the
i.
aminoglycosides,
? alpha 2 region (alpha 2
ii. cephalosporins,
microglobulin,
retinol
binding protein), and
iii. Cyclosporine
? one band in the beta 2
?
Pyelonephritis,
region
(beta
2
?
Interstitial nephritis,
microglobulin)
?
Renal vascular disease,
and
?
Transplant rejection.
Overflow proteinuria
? It is caused by high plasma protein
concentrations that exceed the reabsorptive
capacity of the tubules.
? Common examples include Bence-Jones
Proteins
(multiple
myeloma)
and
myoglobinuria.
? In hemolytic conditions, hemoglobin can
appear in urine (hemoglobinuria)
B. HEMATURIA
? An earliest sign of glomerular damage before the
overt decrease in GFR.
? Intact glomerulus does not allow the passage of RBC.
When severe glomerular damage
RBC leakage occurs
? Detection of microscopic hematuria or RBC casts
confirm glomerular damage
TUBULAR FUNCTION TEST
? These tests are based on tubular reabsorption and
secretion function of kidneys.
? The tubular epithelial cells of nephrons are highly
specialized structure, which selectively reabsorb
water and some substances and secrete other.
1. Specific gravity of urine
? The simplest test of tubular function is the measurement of
specific gravity of urine by a urinometer.
? Normal 1.015-1.025
? This is an indication of osmolality.
? Incase of proteinuria S.G. elevated.
? Earliest manifestation of renal disease may be difficulty in
concentrating the urine.
? Sp.gr.-- excessive water intake, ch.nephritis, Diabetes
Insipidus
? Sp.gr.-- diabetes mellitus, nephrosis, Ch.Renal failure.
? Fixed sp.gr. at 1.010 isosthenuria -- earliest
manifestation of tubular disease / chronic renal failure.
? A defect in concentrating capacity is termed
hyposthenuria.
? The inability to excrete the waste products may be
counterbalanced by large urine output.
? Thus the earliest manifestation of the renal disease
may be difficulty in concentrating urine.
2. Urine Osmolality
? Osmolality of urine varies from 50 mosm/kg in
condition of excessive fluid intake to 1200 mosm/kg in
low fluid intake.
? Random urine sample = 850-900 mosm/kg.
? It is found that the urine (without any protein or high
molecular weight substance) with an osmolality of 800
mosm/kg has a specific gravity of 1.020
? Therefore, measurement of urine osmolality will also
help to assess tubular function
? Plasma osmolality is 285-295 mOsm/kg.
3. WATER DEPRIVATION TEST OR URINE
CONCENTRATION TEST
? 99% of water of glomerular filtrate is reabsorbed during
its passasge through different segment of renal tubule.
Fluid intake is withheld overnight preferably 18 hours
osmolality of 1st urine sample in the morning
If osmolality > 850 mosmol/kg , Sp.Gv- 1.022
Renal concentrating ability is normal/good
? In low ADH activity ( hypothalmic / pituitary
disorder) or nephrogenic diabetes insipidus (lack of
response to ADH)
Osmolality is low and rarely exceeds 300 mosm/kg
(Sp. Gr. 1.010)
4. Urine dilution test
? A normal kidney produce a dilute urine following excessive
water intake.
After an overnight fast and fluid deprivation
Bladder is emptied at 7 am and water load (1200 ml over
the next 30 min) is given
Hourly urine samples are collected for next four hours
The specific gravity of at least one sample should fall to
1.003 and osmolality to 50 mOsm/kg
? Normal person will excrete all the water load with in
4 hours
? Kidneys which are severely damaged cannot excrete a
urine of lower specific gravity than 1.010 or a volume
above 400 ml in this time.
? This test is more sensitive and less harmful than
concentration test
? The test should not be done if there is oedema or renal
failure; water intoxication may result
5. Ammonium chloride loading test or
Urinary Acidification test
? It is indicated in unexplained hyperchloremic
metabolic acidosis
? Acidification defects may occur due to generalized
tubular defects or due to genetically determined
defects in ion pumps
? Enteric coated capsules containing ammonium
chloride at a dose of 0.1 g / kg body wt is given
? In the liver, NH3 is converted to urea and HCl is
produced which is excreted by kidney.
? Urine is collected hourly from 2 to 8 hours after
ingestion.
? At least one sample should have a pH of 5.3
? In type I distal renal tubular acidosis, urinary pH
rarely falls below 6 and never falls below 5.3.
? Liver disease is a contraindication to perform this
test.
FRACTIONAL EXCRETION OF SODIUM
It is a measure of
the percentage of
sodium that gets
excreted in the urine
over
the
total
filtered sodium by
the kidney
URINE ANALYSIS
URINE ANALYSIS
This post was last modified on 30 November 2021