Kidney function test
Functions of kidney
• Maintenance of homeostasis: responsible for
water, electrolyte and acid-base balance
• Excretion of metabolic waste products: end
products of protein and nucleic acids e.g. urea,
creatinine, uric acid etc.
• Retention of substances vital to the body:
glucose, amino acids etc.
• Hormonal function: Erythropoietin, calcitriol,
renin etc
Formation of urine
• Urine is formed by the help of nephrons
• About 1 million nephrones are present in one
kidney
• Nephron contains bowmen’s capsule, proximal
convoluted tubule, loop of henle, distal
convoluted tubule and collecting tubule
• blood supply high-1200ml/min
• 120-125ml/min is filtered which is known as
glomerular filtration rate (GFR)
Formation of urine
Process of urine formation basically involves
two steps
• Glomerular filtration: formation of ultrafiltrate
– waste materials of plasma are filtered
• Tubular reabsorption: formation of pure urine
– PCT & DCT retain water and most of the soluble
constituents of the glomerular filtrate by
reabsorption
• Renal threshold of a substance is the
concentration in blood beyond which it is
excreted in urine
• Renal threshold for glucose is 180mg/dL
• Tubular maximum (Tm): maximum capacity
of the kidneys to absorb a particular
substance
• Tm for glucose is 350 mg/min
Renal function tests
• Glomerular function tests: all the clearance
tests (innulin, creatinine, urea)
• Tubular function test: urine concentration
or dilution test or urine acidification test
• Analysis of blood/serum: blood urea,
serum creatinine, protein and electrolytes
• Urine examination: simple routine
examination of urine for volume, pH,
proteins, blood, ketone bodies, glucose
Why Test Renal Function?
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To identify renal dysfunction.
To diagnose renal disease.
To monitor disease progress.
To monitor response to treatment.
To assess changes in function that may
impact on therapy (e.g. Digoxin,
chemotherapy).
Renal Functions
• Production of urine
– Elimination of metabolic
end products
(Urea/Creatinine)
– Elimination of foreign
materials (Drugs)
– Control of volume &
composition of ECF
• Water and
electrolyte balance
• Acid/Base status
• Endocrine Functions
• Vit D, Erpo, Renin
Signs and Symptoms of Renal Failure
• Symptoms of Uraemia (nausea, vomiting,
lethargy)
• Disorders of Micturation (frequency, nocturia,
dysuria)
• Disorders of Urine volume (polyuria, oliguria,
anuria)
• Alterations in urine composition (haematuria,
proteinuria, bacteriuria, leukocytouria, calculi)
• Pain
• Oedema (hypoalbuminaemia, salt and water
retention)
Biochemical Tests of Renal Function
• Urinalysis
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Appearance
Specific gravity and osmolality
pH
Glucose
Protein
Urinary sediments?
• Measurement of GFR
– Clearance tests
– Plasma creatinine
• Tubular function tests
Role of Biochemical Testing
• Presentation of patients: • Routine urinalysis
• Symptom or physical sign
• Systemic disease with known renal component.
• Effective management of renal disease depends
upon establishing a definitive diagnosis: • Detailed clinical history
• Diagnostic imaging and biopsy
• Role of biochemistry: • Rarely establishes the cause
• Screening for damage
• Monitoring progression.
Urinalysis 1
• Fresh sample = Valid sample.
• Appearance:
– Blood
– Colour (haemoglobin, myoglobin,)
– Turbidity (infection, nephrotic syndrome
• Specific gravity : – Normal is 1.0002-1.030
• pH:
– Normal =acidic, except after meal
Urinalysis 2
• Glucose
– Increased glucose
– Low renal threshold or other tubular disorders
• Proteinuria
– Normal < 200 mg/24h. Urine sticks (+)ve if ≥300mg/L
– Causes:
• overflow (raised plasma Low MW Proteins, Bence
Jones, myoglobin)
• glomerular leak
• decreased tubular reabsorption of protein (RBP,
Albumin)
• protein renal origin
Causes of colouration in urine
Blue Green
Pink-OrangeRed
Methylene Blue Haemoglobin
Red-brown-black
Pseudomonas
Myoglobin
Myoglobin
Riboflavin
Phenolpthalein Red blood cells
Haemoglobin
Porphyrins
Homogentisic Acid
Rifampicin
L–DOPA
Melanin
Methyldopa
Urinalysis 3
• Urine sediments
– Microscopic examination of sediment from freshly
passed urine.
• Looking for cells, casts (Tamm-Horsfall protein), fat
droplets
• Red Cell casts - haematuria - glomerular disease
• White cell cast + polymorphs + bacteriuria =
pylonephrites
• Acute glomerulnephritis = haematuria, cells, casts
Measurement of Glomerular
Filtration Rate (GFR)
• GFR is essential to renal function
• Most frequently performed test of renal
function.
• Measurement is based on concept of
clearance: “The determination of the volume of plasma
from which a substance is removed by
glomerular filtration during it’s passage
through the kidney”
Determination of Clearance
• Clearance = (UxV)/P
Where,
U is the urinary concentration of substance
V is the rate of urine formation (mL/min)
P is the plasma concentration of substance
• Units = volume/unit time (mL/min)
• If clearance = GFR then substance should have
the properties:
– freely filtered by glomerulus
– glomerulus = sole route of excretion from the body (no
tubular secretion or reabsorbtion)
– Non-toxic and easily measurable
Properties of Agents used to
Determine GFR
Property
Urea
Creatinine
Inulin
Not Protein
Bound
Yes
Yes
Yes
Freely Filtered
Yes
Yes
Yes
No secretion or
absorbtion
Flow related
reabsorption
Some secretion
Yes
Constant
endogenous
production rate
Easily Assayed
No
Yes
No
Yes
Yes
No
Inulin GFR
• Gold Standard
• Plant polysacharide
• Complex procedure
– Bolus dose followed by constant infusion
– Timed urines, with bloods taken midpoint of
collection periods, for inulin assay.
– GFR is taken as the mean for each period.
• 1-2%/day of muscle creatine converted to creatinine
• Amount produced relates to muscle mass
• Freely filtered at the glomerulus
• Some tubular excretion.
Creatinine Clearance
• Timed urine collection for creatinine
measurement (usually 24h)
• Blood sample taken within the period of
collection.
• Normal range = 120-145ml/min
Problems: • Practical problems of accurate urine collection
and volume measurement.
• Within subject variability = 11%
Plasma Creatinine Concentration
Difficulties: • Concentration depends on balance between
input and output.
• Production determined by muscle mass
which is related to age, sex and weight.
• High between subject variability but low within
subject.
• Concentration inversely related to GFR.
– Small changes in creatinine within and around the
reference limits = large changes in GFR.
Effect of Muscle Mass on Serum Creatinine
Normal
Muscle
Mass
Normal
Muscle
Mass
Normal
Kidneys
Diseased
Kidneys
Increased
Muscle
Mass
Reduced
Muscle
Mass
Creatinine
Input
Plasma
Pool
Content
Kidney
Output
Normal
Kidneys
Diseased
Kidneys
Acute Renal Failure
Metabolic features:
• Retention of:
– Urea & creatinine
– Na & water
– potassium with hyperkalaemia
– Acid with metabolic
acidosis
Classification of Causes:
• Pre-renal
– reduced perfusion
• Renal
– inflammation
– infiltration
– toxicity
• Post-renal
– obstruction
Pre-renal versus intrinsic ARF
Test
Result
Pre-renal
Renal
Urea & Creatinine Disproportionate
rise in Urea
Tend to rise
together
Protein in urine
Present on
dipstick
testing
Uncommon