Kidney Function Tests Explained

KIDNEY FUNCTION TEST
BY
Ashok B. Giri
Pharm.D (Doctor Of Pharmacy)

INTRODUCTION
 Main organs of excretory /Urinary system
 Paired organ: 02 in number
 Embryonic origin: Mesoderm
 kidneys are bilateral bean-shaped organs, reddish-
brown in colour
 located in the posterior abdomen.
02-Feb-2020©AshokGiriPharmD
2

ANATOMICAL POSITION:
 kidneys lie retroperitoneally (behind the
peritoneum) in the abdomen, either side of the
vertebral column.
 typically extend from T12 to L3
 the right kidney is often situated slightly lower due
to the presence of the liver
 Dimensions: Each Kidney approx. L:11 W:7 B:3
 Weight: 20-35 g
3

AN INTRODUCTION TO THE URINARY SYSTEM:
Produces urine
Transports urine
towards bladder
Temporarily store
urine
Conducts urine
to exterior
4

THE FUNCTION OF URINARYSYSTEM
 Excretion & Elimination:
removal of organic wastes products
from body fluids (urea, creatinine,
uric acid)
 Homeostatic regulation: Acid -
base Balance
 Enocrine function:
Hormones
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 excretion of excess electrolytes, nitrogenous wastes and organic acids
 The maximal excretory rate is limited or established by their plasma
concentrations and the rate of their filtration through the glomeruli
 The maximal amount of substance excreted in urine does not exceed the
amount transferred through the glomeruli by ultrafiltration except in the
case of those substances capable of being secreted by the tubular cells.
A) THE EXCRETORY FUNCTION
6

FUNCTIONAL UNITS: NEPHRONE
B)
C)
•
•
D) Collecting Duct
Nephr structure
A)
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URINE FORMATION
Urine formation requiers :
a) Glomerular Filtration
Due to differences in pressure water, small molecules
move from the glomerulus capillaries into the
glomerular capsule
b) Tubular reabsorption
many molecules are reabsorbed from the nephron
into the capillary (diffusion, facilitated diffusion,
osmosis, and active transport)
i.e. Glucose is actively reabsorbed with transport
carriers.
If the carriers are overwhelmed glucose appears in
the urine indicating diabetes
c) Tubularsecretion
Substances are actively removed from blood and
added to tubular fluid (active transport)
ie. H+, creatinine, and some drugs are moved by
active transport from the blood into the distal
convoluted tubule
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 Measurement of GFR
□ Clearance tests
□ Plasma creatinine
□ Urea, uric acid and β2‐microglobulin
 Renal tubular function tests
□ Osmolality measurements
□ Specific proteinurea
□ Glycouria
□ Aminoaciduria
 Urinalysis
□ Appearance
□ Specific gravity and osmolality
□ pH
□ osmolality
□ Glucose
□ Protein
□ Urinary sediments
BIOCHEMICAL TESTS OF RENAL FUNCTION
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 Older age
 Family history of Chronic Kidney disease (CKD)
 Decreased renal mass
 Low birth weight
 Diabetes Mellitus (DM)
 Hypertension (HTN)
 Autoimmune disease
 Systemic infections
 Urinary tract infections (UTI)
 Nephrolithiasis
 Obstruction to the lower urinary tract
 Drug toxicity
WHEN SHOULD YOU ASSESS RENALFUNCTION?
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Measurement of GFR
□Clearance tests
□Plasma creatinine
□Urea, uric acid andβ2-microglobulin
BIOCHEMICAL TESTS OF RENAL
FUNCTION
11

GFR can be estimated by measuring the urinary excretion of a substance that is completely filtered
from the blood by the glomeruli and it is not secreted, reabsorbed or metabolized by the renal
tubules.
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 the glomeruli but
neither reabsorbed nor secreted by other regions of the nephron can be used to measure GFR.
Inulin
The Volume of blood from which inulin is cleared or completely removed in one minute is
known as the inulin clearance and is equal to the GFR.
Measurement of inulin clearance requires the infusion of inulin into the blood and is not
suitable for routine clinical use
GFR =
Pinulin
(Uinulin  V)
V is not urine volume, it is urine flow rate
MEASUREMENT OF GLOMERULAR
FILTRATION RATE
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The most test is based on the
measurement of creatinine.
Small quantity of creatinine is reabsorbed by the tubules and
other quantities are actively secreted by the renal tubules
 So creatinine clearance is approximately 7%
greater than inulin clearance.
The difference is not significant when GFR is normal but when
the GFR is low (less 10 ml/min), tubular secretion makes the
major contribution to creatinine excretion and the creatinine
clearance significantly overestimates the GFR.
CREATININE CLEARANCE AND CLINICAL
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An estimate of the GFR can be calculated from the creatinine content of a 24-hour
urine collection, and the plasma concentration within this period.
The volume of urine is measured, urine flow rate is calculated (ml/min) and the
assay for creatinine is performed on plasma and urine to obtain the concentration in
mg per dl or per ml.
Creatinine clearance in adults is normally about of 120 ml/min,
The accurate measurement of creatinine clearance is difficult, especially in outpatients,
since it is necessary to obtain a complete and accurately timed sample of urine
CREATININE CLEARANCE CLINICALUTILITY
14

The 'clearance' of creatinine from plasma is directly related to the
GFR if:
The urine volume is collected accurately
There are no ketones or heavy proteinuria present to interfere
with the creatinine determination.
It should be noted that the GFR decline with age (to a greater extent
in males than in females) and this must be taken into account when
interpreting results.
REATININE CLEARANCE AND CLINICALUTILITY
15

Catabolism of proteins and nucleic acids results in formationof so
called nonprotein nitrogenous compounds.
Protein  Proteolysis, principally enzymatic Amino acids
 Transamination and oxidative deamination
Ammonia
 Enzymatic synthesis in the “urea cycle”
Urea
MEASUREMENT OF NONPROTEIN NITROGEN-
CONTAINING COMPOUNDS
16

Many renal diseases with various glomerular, tubular, interstitial or vascular damage can
cause an increase in plasma urea concentration.
The reference interval for serum urea of healthy adults is 5-39 mg/dl. Plasma
concentrations also tend to be slightly higher in males than females. High protein diet causes
significant increases in plasma urea concentrations and urinary excretion.
Measurement of plasma creatinine provides a more accurate assessment than urea
because there are many factors that affect urea level.
Nonrenal factors can affect the urea level (normal adults is level 5-39 mg/dl) like:
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 its synthetic analogous
PLASMA UREA
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• States associated with elevated levels of urea
in blood are referred to as uremia or azotemia.
• Causes of urea plasma elevations:
Prerenal: renal hypoperfusion
Renal: acute tubular necrosis
Postrenal: obstruction of urinary flow
CLINICAL SIGNIFICANCE
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Renal handling of uric acid is complex and involves four sequential steps:
Glomerular filtration of virtually all the uric acid in capillary plasma
entering the glomerulus.
Reabsorption in the proximal convoluted tubule of about 98 to 100%
of filtered uric acid.
Subsequent secretion of uric acid into the lumen of the distal portion
of the proximal tubule.
Further reabsorption in the distal tubule.
 Hyperuricemia is defined by serum or plasma uric acid concentrations higher
than 7.0 mg/dl (0.42mmol/L) in men or greater than 6.0 mg/dl (0.36mmol/L)
in women
URICACID
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β2-microglobulin is a small peptide (molecular weight 11.8 kDa),
It is present on the surface of most cells and in low concentrations in the
plasma.
It is completely filtered by the glomeruli and is reabsorbed and catabolized
by proximal tubular cells.
The plasma concentration of β2-microglobulin is a good index of GFR in
normal people, being unaffected by diet or muscle mass.
It is increased in certain malignancies and inflammatory diseases.
Since it is normally reabsorbed and catabolized in the tubules, measurement
of β2-microglobulin excretion provides a sensitive method of assessing
tubular integrity.
PLASMA Β2-MICROGLOBULIN
20

RENAL TUBULAR FUNCTIONTESTS
• To ensure that important constituents such as water, sodium, glucose and
a.a. are not lost from the body, tubular reabsorption must be equally
efficient
• Compared with the GFR as an assessment of glomerualr function, there are
no easily performed tests which measure tubular function in quantitative
manner
• Investigation of tubular function:
1. Osmolality measurements in plasma and urine; normal urine: plasma
osmolality ratio is usually between 1.0-3.0
2. Specific proteinuria
3. Glycosuria
4. Aminoaciduria
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Proteinuria may be due to:
1.An abnormality of the glomerular basement membrane.
2. Decreased tubular reabsorption of normal amounts of filtered proteins.
3. Increased plasma concentrations of free filtered proteins.
4.Decreased reabsorption and entry of protein into the tubules consequent to tubular epithelial
cell damage.
Measurement of individual proteins such as β2-microglobulin have been used in the early
diagnosis of tubular integrity.
With severe glomerular damage, red blood cells are detectable in the urine (haematuria), the red
cells often have an abnormal morphology in glomerular disease.
 Haematuria can occur as a result of lesions anywhere in the urinary tract,
ASSESSMENT OF GLOMERULAR
INTEGRITY
22

Urinalysis is important in screening for d i s e a s e  is routine test for every patient, and not
just for the investigation of renal diseases
Urinalysis comprises a range of analyses that are usually performed at the point of care rather
than in a central laboratory.
Urinalysis is one of the commonest biochemical tests performed outside the laboratory.
Examination of a
patient's urine should not
be restricted to
biochemical tests.
URINALYSIS
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– This is a semi-quantitative measure of concentration.
– A higher specific gravity indicates a more concentratedurine.
– Assessment of urinary specific gravity usually just confirms the impression gained
by visually inspecting the colour of the urine. When urine concentration needs tobe
quantitated,
URINALYSIS: SPECIFIC GRAVITY
24

 Osmolality serves as general marker of tubular function.
Because the ability to concentrate the urine is highly
affected by renal diseases.
 This is conveniently done by determining the
osmolality, and then comparing this to the plasma.
 If the urine osmolality is 600mosm/kg or more, tubular
function is usually regarded as intact
 When the urine osmolality does not differ greatly from
plasma (urine: plasma osmolality ratio=1), the renal
tubules are not reabsorbing water
URINALYSIS: OSMOLALITY MEASUREMENTS IN
PLASMA AND URINE
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pH
-Urine is usually acidic
-Measurement of urine pH is useful in suspected drug toxicity, abuse.., or where there
is an unexplained metabolic acidosis (low serum bicarbonate or other causes…).
Urine sediments
-Microscopic examination of sediment from freshly passed urine involves looking for
cells, casts, fat droplets
-Blood: haematuria is consistent with various possibilities ranging from malignancy
through urinary tract infection to contamination from menstruation.
- Red Cell casts could indicate glomerular disease
- Crystals
-Leucocytes in the urine suggests acute inflammation and the presence of aurinary
tract infection.
URINALYSIS
26

To maintain water homeostasis, the kidneys must produce urine in a volume
precisely balances water intake and production to equal water loss through extra
renal routes.
Minimum urine volume is determined by the solute load to be excreted whereas
maximum urine volume is determined by the amount of excess water that must be
excreted
URINE VOLUME
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ANY QUESTIONS
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Kidney Function Tests Explained

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