kidney function tests

Kidney Function Tests

1- Excretion of metabolic waste products & foreign chemicals2- Regulation of water & électrolyte balance 3- Regulation of acid - base balance4- Regulation of arterial blood pressure5- Production of erythropoietin & activation of vitamin D6- Other metabolic functions (as gluconeogenesis, etc..)

Main Functions of the Kidney

Renal DiseasesOverview1- 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 diseases2- Glomerular diseases3- Tubular & interstitial diseases4- Obstructive uropathies

• 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

Pre-renal diseases

Causes: Idiopathic Secondary: neoplasia, autoimmune disease, drugs, infections, genetic

Two general patterns (with considerable overlap in some diseases) are seen:

Nephritic patternAssociated 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 patternNot 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.

Glomerular 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

Tubular & interstitial diseases

Obstructive Uropathy

Obstruction to the flow of urine can occur anywhere from the renal pelvis to the urethra.

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

Nephrotic syndrome is diagnosed by:Plasma Proteins Electrophoresis

Biochemical Investigations of kidney Functions

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

Indications for assessing renal functions

Assessment of Kidney Functions

1- Assessment of Glomerular Functions2- Assessment of Tubular Functions

Assessment of glomerular filtration rate (GFR) is used an index of glomerular functions

Measurement of GFR

Clearance Tests Blood Creatinine Blood Urea Blood Uric Acid Blood β2-microglobulin

Biochemical Investigations of Glomerular Functions

Glomerular FiltrationIs 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.

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 VClearance (ml/min) = __________________________________

PU 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)


Clearance Tests:Accurate measurement of GFR by clearance tests requires determination of the

concentration in blood & urine of a substance that is: Freely filtered at glomeruli Neither reabsorbed nor secreted by tubules. Its concentration in plasma needs to remains constant throughout the period of

urine collection. Better if the substance is present endogenously Easily measured.

Creatinine meets most of these criteria


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


Inulin clearance testMeasurement 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 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

Plasma Creatinine Vs. Creatinine Clearance

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 Urea

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

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:• Excessive intake of diets containing nucleic acids (esp. red meat).• 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

Blood Uric Acid cont.

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.

Plasma β2-microglobulin

Renal tubular functions is assessed by: Urine Osmolality Measurements Urine pH Urine Volume Urine Specific Gravity Urine Appearance & Colour Urine Protein Amount Urine Glucose Amount Measurement (Glucosuria) Urine Amino Acids (Aminoaciduria)

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)

– 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

– If the urine osmolality is 600 mosm/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 (due to a tubular disease)

A patient with polyuria due to chronic renal failure is unable to produce either a dilute or concentrated urineInstead urine osmolality is generally within 50 mmol/kg of the plasma osmolality

Urine osmolality cont.

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 collectionQuantitative urine protein measurements should always be made on complete

24-hour urine collections. Types of proteinuriaGlomerular proteinuria Tubular proteinuria Overflow proteinuria

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

Glomerular 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.

Tubular 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

Overflow Proteinuria

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