Transcript Kidney Function Testing - Yola

Kidney Function Tests
Main Functions of the Kidney
1- Excretion of metabolic waste products & foreign chemicals
2- Regulation of water & électrolyte balance
3- Regulation of acid - base balance
4- Regulation of arterial blood pressure
5- Production of erythropoietin & activation of vitamin D
6- Other metabolic functions (as gluconeogenesis, etc..)
Renal Diseases
Overview
1- Many renal diseases affect renal functions
2- In some renal diseases, several functions are affected
3- In other renal diseases, there is selective impairment of
glomerular function or one or more of the tubular functions
Most types of renal diseases cause destruction of
complete nephron
Major causes of renal diseases
1- Pre-renal diseases
2- Glomerular diseases
3- Tubular & interstitial diseases
4- Obstructive uropathies
Pre-renal diseases
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The two major causes of reduced renal perfusion:
Volume depletion (reduced volume of blood to the glomeruli)
and/or relative hypotension
• Prerenal disease is most commonly associated with an acute time course.
• However, among patients with chronic kidney disease, the addition of a
prerenal process may result in acute renal dysfunction
Glomerular diseases
Causes:
 Idiopathic
 Secondary: neoplasia, autoimmune disease, drugs, infections, genetic
 Two general patterns (with considerable overlap in some diseases) are seen:
 Nephritic pattern
Associated with inflammation on histological examination
Urine:
Active urine sediment with RBCs, WBCs, granular, red cell & other cellular casts
Variable degree of proteinuria (mild to moderate in most cases).
 Nephrotic pattern
Not associated with inflammation on histological examination
Urine:
Proteinuria (moderate to severe . Most cases heavy proteinuria)
An inactive urine sediment with few RBCs &WBCs cells or casts.
Tubular & interstitial diseases
The tubular and interstitial diseases affecting the kidney can be divided into
those that produce acute and chronic disease:
 Acute tubulointerstitial disorders as acute tubular necrosis
 Chronic tubulointerstitial disorders as polycystic kidney disease
Obstructive Uropathy
Obstruction to the flow of urine can occur anywhere from the renal pelvis to
the urethra.
Nephrotic syndrome
The nephrotic syndrome is caused by renal diseases that increase the permeability across the
glomerular filtration barrier.
It is classically characterized by four clinical features, but the first two are used diagnostically
because the last two may not be seen in all patients.
1- Proteinuria : Urinary protein excretion greater than 50 mg/kg per day (heavy proteinuria)
2- Hypoalbuminaemia : Serum albumin concentration less than 3 g/dL (30 g/L)
3- Edema
4- Hyperlipidemia: increased cholesterol in blood
Nephrotic syndrome is diagnosed by:
Plasma Proteins Electrophoresis
Biochemical Investigations of kidney Functions
Indications for assessing renal functions
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Routine checkup
Older age
Chronic renal diseases
Decreased renal mass
Diabetes mellitus (DM)
Hypertension (HTN)
Autoimmune disease (as SLE, etc)
Systemic infections
Urinary tract infections (UTI)
Nephrolithiasis (renal stones)
Obstruction to the lower urinary tract (e.g. prostatic causes)
Drug toxicity
Assessment of Kidney Functions
1- Assessment of Glomerular Functions
2- Assessment of Tubular Functions
Biochemical Investigations
of Glomerular Functions
Glomerular Filtration
Is The first step in the production of urine
Glomerular Filtration Rate (GFR)
The amount of filtrate that flows out of all the renal
corpuscles of both kidneys every minute
In the normal adult, this rate is about 120 ml/minute
i.e. about 180 liters / day
GFR provides a useful index of the number of functioning glomeruli
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, not reabsorbed & not metabolized by the
renal tubules.
Measurement of glomerular Filtration Rate
Clearance Tests:
Clearance is defined as the volume of plasma completely cleared from a
substance excreted in urine per minute
Normal Range:
About 110-120 ml/min in age of 20-40 years
Falls slowly & progressively to about 70 – 80 ml/min in ages over 80 years
More in males
Measurement of glomerular Filtration Rate
U X V
Clearance (ml/min) =
__________________________________
P
U is the concentration of substance in urine (in mmol/L)
V is urine flow rate (in ml/min)
P is the concentration of substance in bloodin mmol/L)
Measurement of glomerular Filtration Rate
Clearance Tests:
Accurate measurement of GFR by clearance tests requires determination of the
concentration in blood & urine of a substance that is:
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Freely filtered at glomeruli
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Neither reabsorbed nor secreted by tubules.
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Its concentration in plasma needs to remains constant throughout the period of
urine collection.
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Better if the substance is present endogenously
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Easily measured.
Creatinine meets most of these criteria
Measurement of glomerular Filtration Rate
Creatinine Clearance Test
Why Creatinine is used for testing clearance?
 Creatinine is endogenously produced & is proportional to muscle mass
1 to 2% of muscle creatine spontaneously converts to creatinine daily
Creatinine production is not affected by diet (no exogenous factors)
 Creatinine is freely filtered at glomeruli at a constant rate.
 Creatinine is not significantly reabsorbed by renal tubules
However, 10% of urinary creatinine is secreted by renal tubules (not
significant)
 Blood levels of creatinine are maintained within narrow limits
Measurement of glomerular Filtration Rate
Inulin clearance test
Measurement of inulin clearance requires the infusion of inulin into the blood and is not suitable
for routine clinical use
Advantage of inulin clearance test over creatinine
clearance test:
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 (gives values greater than real ).
Plasma Creatinine Vs. Creatinine Clearance
• Plasma creatinine correlates with GFR as does creatinine clearance in patients with
renal disease
• Measurements of plasma creatinine are as effective in detecting early renal disease as
creatinine clearance
• Plasma creatinine remains fairly constant throughout adult life while creatinine
clearance decreases with aging
• Plasma creatinine measurements enable the progress of renal disease to be followed
with better accuracy than creatinine clearance
Creatinine Clearance is ONLY recommended (rather than serum creatinine) in:
 Patients with early (minor) renal disease
 Assessment of possible kidney donors
 Detection of renal toxicity of some nephrotoxic drugs
Blood Urea
Urea is the major nitrogen-containing metabolic product of protein catabolism in humans.
Urea is filtered freely by the glomeruli
Plasma urea concentration is often used as an index of renal glomerular function
Non renal factors can affect the urea level (normal adults is level 5-39 mg/dl) as:
• Mild dehydration
• High protein diet (exogenous production factor)
• Increased protein catabolism (as in Cushing`s disease, DM, starvation, thyrotoxicosis)
• Reabsorption of blood proteins after a GIT hemorrhage
 Accordingly, measurement of plasma creatinine provides a more accurate
assessment than blood urea because there are many factors that affect urea
level rather than renal causes
Blood Uric Acid
Renal handling of uric acid is complex and involves four sequential
steps:
 Filtration of virtually all the uric acid in capillary plasma entering the glomeruli
• Reabsorption in the proximal convoluted tubule of about 98 to 100% of filtered uric acid
• Secretion of uric acid into the lumen of the distal portion of the proximal tubule
• Further reabsorption in the distal tubule.
Blood Uric Acid cont.
In human, uric acid is the end product of the catabolism of the purine bases in in nucleic
acids (mainly DNA & RNA).
Approximately 75% of uric acid excreted is lost in the urine (remainder by GIT mainly)
Hyperuricemia
is defined by serum or plasma uric acid concentrations higher than 7.0 mg/dl in men or
greater than 6.0 mg/dl in women
Causes of hyperuricemia:
1- Overproduction of uric acid:
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Excessive intake of diets containing nucleic acids (esp. red meat).
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Increased cellular breakdown (as in cancer, etc)
• Genetic causes (as in Von Gierke`s Disease)
2- Renal impairment (glomerular diseases)
SO YOU HAVE TO EXCLUDE OTHER RENAL CAUSES FOR HYPERURICEMIA
Plasma β2-microglobulin
β2-microglobulin is:
1- A small protein
2- Present on the surface of most cells and in low concentrations in the plasma.
3- Completely filtered by the glomeruli & is reabsorbed & catabolized by proximal tubular cells.
Results of measuring blood levels of β2-microglobulin:
1- Is a good index of GFR in normal people (as it is not affected by diet or muscle mass)
2- Since it is normally reabsorbed and catabolized in the tubules, β2-microglobulin blood level
provides a sensitive method of assessing tubular functions.
3- BUT:
It is increased in certain malignancies and inflammatory diseases.
Biochemical Investigations
of Tubular Functions cont.
Urine osmolality
Osmolality: weight of solutes/ weight of solvent
Urine osmolality: Concentration of all solutes (weight of all solutes / weight of urine)
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Is a correct measure of the concentrating power of the kidney i.e. ability of the
kidney to reabsorb water
– Is done by determining the urine osmolality & then comparing this to the plasma.
– Is highly affected by renal diseases. (the ability to concentrate the urine is affected )
So, urine osmolality serves as general marker of tubular function.
Results of urine osmolality
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If the urine osmolality is 600 mosm/kg or more, tubular function is usually regarded as intact
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When the urine osmolality does not differ greatly from plasma (urine: plasma osmolality ratio=1),
the renal tubules are not reabsorbing water (due to a tubular disease)
Urine osmolality cont.
A patient with polyuria due to chronic renal failure is unable to produce
either a dilute or concentrated urine
Instead urine osmolality is generally within 50 mmol/kg of the plasma
osmolality
Proteinuria
Normally:
 Glomerular filtrate contains about 30mg/Litre protein; this corresponds to a total
filtered load of about 5g/24hours
 Since only less than 200 mg protein is normally excreted in the urine each day, tubular
reabsorption must be very efficient
Proteinuria
Normal protein amount n urine is < 200 mg/24hours urine collection
Quantitative urine protein measurements should always be made on complete
24-hour urine collections.
Types of proteinuria
Glomerular proteinuria
Tubular proteinuria
Overflow proteinuria
Glomerular Proteinuria
• Is caused by increased filtration of high molecular weight proteins (such as
albumin) across the glomerular capillary wall.
 Example:
1- Diabetic nephropathy
2- Nephrotic syndrome
Tubular Proteinuria
 Overview
Low molecular weight molecules such as smaller proteins (ß2-microglobulin,
immunoglobulin light chains, retinol-binding protein ) & amino acids have molecular
weights that are generally less than 25,000 in comparison to the 69,000 molecular
weight of albumin.
 Normally
Smaller molecules (including smaller proteins & amino acids) can be filtered across the
glomeruli & are then almost completely reabsorbed in the proximal tubule.
 In tubular diseases:
Interference with proximal tubular reabsorption can lead to increased excretion of
these smaller proteins & amino acids (aminoaciduria)
N.B. aminoaciduria due to inborn errors of amino acids metabolism must be excluded
to diagnose tubular defects.
Overflow Proteinuria
 Increased excretion of low molecular weight proteins can occur with
marked overproduction of a particular protein, leading to increased
glomerular filtration and excretion of this protein
 This is due to (almost all causes):
1- Immunoglobulin light chains in multiple myeloma
2- lysozymes in acute myelomonocytic leukemia & in rhabdomyolysis
3- Hemoglobin in intravascular hemolysis