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TESTS TO MEASURE KIDNEY FUNCTION, DAMAGE AND DETECT ABNORMALITIES

Dr. Parin Hedayati

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An Introduction to the Urinary System

Produces urine

Transports urine towards bladder

Temporarily store urine

Conducts urine to exterior

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• Healthy kidneys remove wastes and excess fluid from the blood. • Blood and urine tests show how well the kidneys are

doing their job. • Urine tests can show how quickly body wastes are

being removed and whether the kidneys are leaking abnormal amounts of protein.

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The Function of Urinary System

Excretion & Elimination: removal of organic wastes products

from body fluids (urea, creatinine, uric acid)

Homeostatic regulation: Water -Salt Balance Acid - base BalanceEnocrine function:

Hormones

A)

B)

C)

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Kidney – basic data

•Urine excreted daily in adults:about 1.5L•Kidneys only recieve 1% of total body weight•The renal blood flow= 20% of cardiac output•Plasma renal flow= PRF about 600 mL/Min./1.73 M2

•Reflects two processes •Ultrafiltration (GFR): 180 L/day•Reabsorption: >99% of the amount filtered

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Kidney Function

•A plumbers view

Filter

Processor

InputArterial

OutputVenous

OutputUrine

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How do you know it’s broken?

• Decreased urine production

• Clinical symptoms

• TestsFilter

Processor

InputArterial

OutputVenous

OutputUrine

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Where can it break?

Pre-renal

Renal (intrarenal)

Post-renal (obstruction)

Filter

Processor

InputArterial

OutputVenous

OutputUrine

Causes of kidney functional disorders

• Pre-renal e.g. decreased intravascular volum

• Renal e.g. acute tubular necrosis

• Postrenal e.g. ureteral obstruction

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Why Test Renal Function?

•To identify renal dysfunction.•To diagnose renal disease.•To monitor disease progress.•To monitor response to treatment.

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When should you assess renal function?Older ageFamily history of CKDDecreased renal massLow birth weightDiabetes Mellitus (DM)Hypertension (HTN)Autoimmune diseaseSystemic infectionsUrinary tract infections (UTI)NephrolithiasisObstruction to the lower urinary tractDrug toxicity

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Biochemical Tests of Renal Function Measurement of GFR

Clearance tests Plasma creatinine

Renal tubular function tests Osmolality measurements Specific proteinurea Glycouria Aminoaciduria

Urinalysis Appearance Specific gravity and osmolality pH osmolality Glucose Protein Urinary sediments

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Biochemical Tests of Renal FunctionMeasurement of GFR

Clearance testsPlasma creatinine

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.

Inulin

GFR =(U V)

P

inulin

inulin

Measurement of glomerular

filtration rate

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Biochemical Tests of Renal Function

Measurement of GFR Clearance testsPlasma creatinine Urea, uric acid and β2-

microglobulin

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• The normal value for GFR is 90 or above.• A GFR below 60 is a sign that the kidneys are not working

properly. • A GFR below 15 indicates that a treatment for kidney failure,

such as dialysis or a kidney transplant, will be needed.

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1 to 2% of muscle creatine spontaneously converts to creatinine daily and released into body fluids at a constant rate.

Endogenous creatinine produced is proportional to muscle mass, it is a function of total muscle mass the production varies with age and sex

Dietary fluctuations of creatinine intake cause only minor variation in daily creatinine excretion of the same person.

Creatinine released into body fluids at a constant rate and its plasma levels maintained within narrow limits Creatinine clearance may be measured as an indicator of GFR.

Creatinine

The most frequently used clearance 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 utility

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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.

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 clinical utility

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Use of Formulae to Predict Clearance

• Formulae have been derived to predict Creatinine Clearance from Plasma creatinine.

• Plasma creatinine derived from muscle mass which is related to body mass, age, sex.

• Cockcroft & Gault Formula CC =K [(140-Age) x weight(Kg))] / serum Creatinine (mg/dL)

k = 1 for males & 0.85 for females

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Urea is the major nitrogen-containing metabolic product of protein

catabolism in humans,

Its elimination in the urine represents the major route for

nitrogen excretion.

More than 90% of urea is excreted through the kidneys, with

losses through the GIT and skin

Urea is filtered freely by the glomeruli

Urea production is increased by a high protein intake and it is

decreased in patients with a low protein intake or in patients with

liver disease.

Plasma Urea

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Many renal diseases with various glomerular, tubular, interstitial or vascular damage

can cause an increase in plasma urea concentration. The reference interval for serum BUN 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.

Plasma Urea

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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

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Urinalysis

• Appearance - blood, colour, turbidity.• Specific gravity - sticks measure ionic particles only, not glucose.• pH - normally acidic, except after a meal.• Glucose - the presence of glucose in urine may indicate increased

blood glucose, or tubular disorder.• Proteinuria - the presence of protein in the urine may be caused by

glomerular leak, raised serum low-molecular weight proteins, Bence Jones' proteins, myoglobulin, or protein of renal origin. •Microscopy - urinary tract infection will show polymorphs with no

casts; acute glomerulonephritis will show cells and casts; chronic glomerulonephritis shows little sediment.

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Imaging Tests

• Ultrasound• This test uses sound waves to get a picture of the kidney. It

may be used to look for abnormalities in size or position of the kidneys or for obstructions such as stones or tumors.

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• CT Scan• This imaging technique uses contrast dye to picture the

kidneys. It may also be used to look for structural abnormalities and the presence of obstructions.

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kidney Biopsy

• A biopsy may be done occasionally for one of the following reasons:

1. to identify a specific disease process and determine whether it will respond to treatment

2. to evaluate the amount of damage that has occurred in the kidney

3. to find out why a kidney transplant may not be doing wellA kidney biopsy is performed by using a thin needle with a sharp cutting edge to slice small pieces of kidney tissue for examination under a microscope.

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Urine Tests

• Some urine tests require only a couple of tablespoonfuls of urine. But some tests require collection of all urine produced for a full 24 hours. A 24-hour urine test shows how much urine your kidneys produce in one day. The test also can give an accurate measurement of how much protein leaks from the kidney into the urine in one day.

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MICROALBUMINURIA

•This is a more sensitive dipstick test, which can detect a tiny amount of protein called albumin in the urine. •People who have an increased risk of developing

kidney disease, such as those with diabetes or high blood pressure, should have this test if their standard dipstick test for proteinuria is negative.

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Albuminuria-to-creatinine ratio (ACR).

• Albuminuria occurs when there are higher amounts of a type of protein called albumin in the urine, It is a common marker of kidney damage. The ratio of albumin-to-creatinine is recommended as the best method to determine albuminuria. • All patients with CKD should be tested for albuminuria at least

annually.• You should also get tested if you are at risk for kidney disease (have

diabetes, high blood pressure, or family history of diabetes, high blood pressure or kidney failure).