Renal Clearance

Clearance

20 20 20 20 20 20 20 20 20 20

4 4 4 4 4 4 4 4 4 4

40

1 2 3 4 5 6 7 8 9 10

20 20 20 20 20 20 20 20 2020

4 4 4 4 4 4 4 4 4 4

40

Was any of the carriages completely cleared? No

But can we say that it is as if some carriages were completely cleared?

Yes

If so, how many carriages were completely cleared? 2

20 20 20 20 20 20 20 20 20 20

4 4 4 4 4 4 4 4 4 4

40

Clearance of the train is 2 carriages / station

Remember –• It is not real (it is only as if)• It is related to the train (not the number of passengers)

20 20 20 20 20 20 20 20 20 20

4 4 4 4 4 4 4 4 4 4

40Clearance is -

• Number of carriages of the train cleared of passengers

• The minimum number of carriages needed to supply the number of passengers getting off at the station

OR

• The number of carriages that contained the number of passengers getting off the train

20 20 20 20 20 20 20 20 20 20

4 4 4 4 4 4 4 4 4 4

40

Calculation of clearance -

number of passengers going out of the station number of passengers in each carriage

Apply to plasma and kidney –

Kidney

Solute X excreted

Plasma comes into kidney withmore solute X

Plasma goes out of the kidney withless solute X

Apply to plasma and kidney –

Kidney

Excretion of the solute X

Plasma comes into kidney withmore solute X

Plasma goes out of the kidney withless solute X

Clearance of the solute X =Amount of solute X excreted

Concentration of solute X in plasma

Renal clearance is taken as PER MINUTE

Renal Clearance of a substance is -

• Volume of plasma cleared of the substance by the kidney in one minute

• The minimum volume of plasma needed to supply the amount of substance excreted by the kidney in one minute

OR

• The volume of plasma that contained the amount of substance excreted by the kidney in one minute

Renal clearance of a substance

Total substance excreted in 1 minuteConcentration of substance in plasma

Conc. of substance in urine x Vol. of urine excreted in 1 min

Concentration of substance in plasma

U x V

P

U – concentration of the substance in urine

V – volume of urine produced in 1 minute

P – concentration of the substance in plasma

Unit of renal clearance

U x V P

U – concentration of the substance in urine – mmol/ml

V – volume of urine produced in 1 minute – ml/min

P – concentration of the substance in plasma – mmol/ml

mmol/ml x ml/min mmol/min mmol/ml mmol/ml

Unit of renal clearance is ml/min

= ml/min=

Warning: when performing the calculation make sure that units of U, V and P are similar!

Renal Clearance of a substance - determination

U x V P

U – concentration of the substance in urine – collect urine and measure the concentration

V – volume of urine produced in 1 minute – collect urine for 24 hours and calculate urine output per minute; more accurate asthe output varies throughout the day

P – concentration of the substance in plasma – collect blood during those 24 hours and measure the concentration

Significance of clearance

Measurement of clearance can be used to

determine

1.Glomerular filtration rate – thereby assessing glomerular function

2.Renal plasma/blood flow – not routinely performed

Significance of clearance

1. Glomerular filtration rate – the clearance of a substance freely filtered at the glomerulus but not reabsorbed or secreted in the tubules is the value of GFR

2. Renal plasma/blood flow – the clearance of a substance filtered at the glomerulus and completely secreted by the tubules is the same as renal plasma flow

Significance of clearance

Consider a substance handled by the kidney in the following manner -

1. Freely filtered at glomerulus

2. Completely secreted by tubules

The amount of substanceexcreted comes from the entire plasma flowing through the kidney

Significance of clearance

1. Freely filtered at glomerulus

2. Completely secreted by tubules

The amount of substanceexcreted comes from the entire plasma flowing through the kidney

Calculate the clearance of the substanceU x V P= total plasma flow through the kidney

Significance of PAH clearance

Para amino hippuric acid (PAH) has these characteristics (at low concentrations)

Clearance of PAH = Renal plasma flow

Total plasma flow? No, some blood may bypass the nephrons

Clearance of PAH = Effective renal plasma flow

Total renal plasma flow is about 5 -10% more than effective renal plasma flow

Significance of PAH clearance

If plasma flow is known, blood flow can be calculatedFor this haematocrit needs to be known

clearance of PAH

= Effective Renal blood flow

For example: if PAH clearance is 600ml/min, and haematocrit 40%,

600 / (1 - 40%)Effective Renal blood flow = =600 x 100 60

1 - haematocrit

Significance of clearance

A substance handled by the kidney in the following manner-

1.Freely filtered at glomerulus

2.Not absorbed or secreted by tubules

The amount of substanceexcreted comes entirelyfrom the glomerular filtrate

The amount of substance excreted in 1 minute will come from the glomerular filtrate formed in 1 minute (GFR)

Significance of clearance

A substance handled by the kidney in the following manner-

Clearance of the substance when calculated will give the volume of plasma that contains the amount of substance excreted in 1 minute

Freely filtered at glomerulus

Not absorbed or secreted by tubules

The amount of substanceexcreted comes entirely from the glomerular filtrate

Significance of clearance

The substance excreted comes entirely from the glomerular filtrate

Comes from the glomerular filtrate in 1 minute (GFR)=

the amount of substance

excreted in 1 minute

comes from volume of plasma cleared of the substance in 1 minute (Renal clearance)

=

Clearance as a measure of GFR

The clearance of a substance freely filtered at the glomerulus and not reabsorbed or secreted will be the same as the GFR

Measurement of GFR

Properties of an ideal substance whose clearance mat be determined to measure GFR –

• Freely filtered at the glomerulus• Not reabsorbed by the tubules• Not secreted by the tubules• Not metabolised by the nephron• Not toxic to the body• Does not affect renal function, particularly

glomerular function• Easily measured in the plasma and urine• Found in the body

Clearance as a measure of GFR

The clearance of a substance freely filtered at the glomerulus and not reabsorbed or secreted will be the same as the GFR

The best example of such a substance is INULINInulin clearance, therefore, is the same value as GFR

Measurement of GFR

Inulin as an ideal substance for measuring GFR –

Freely filtered at the glomerulus Not reabsorbed by the tubules Not secreted by the tubules Not metabolised by the nephron Not toxic to the body Does not affect renal function, particularly

glomerular function Easily measured in the plasma and urine Found in the body

Measurement of GFR

Inulin as an ideal substance for measuring GFR –

Found in the body

As inulin is not found in the body it needs to be infused –Associated with risks and restrictions for the person

Alternate substances for measurement of GFR

Creatinine for measuring GFR –(source of creatinine : muscles)

Found in the body

Has a major advantage over inulin as no infusion is necessary

However –Creatinine is secreted in small amounts – tends to

overestimate GFRThe method of measuring serum creatinine gives a

falsely higher value (slight) – tends to underestimate GFR

Creatinine clearance

Commonly performed clearance estimationA good indicator of glomerular function

Parameters measured –• Serum creatinine concentration• 24-hour urine volume• Urine creatinine concentration

Clearance ratio

If the clearance of a substance is :

1. Less than creatinine clearanceReabsorption occurs? Secretion

2. More than creatinine clearanceSecretion occurs? Reabsorption

Serum creatinine

Could serum creatinine be a substitute for creatinine clearance?

Measuring serum creatinine is much easier than determining creatinine clearance

Reasoning may be –? if GFR decreases creatinine excretion decreases? then serum creatinine level increases? Increasing serum creatinine will indicate decreasing GFR

Is this really so?

GFR and plasma creatinine

When GFR falls, plasma creatinine increases but not proportionately – the relationship is not linear

When GFR falls from normal levels

• At lower levels of GFR even small decreases in GFR cause large increases in plasma creatinine

• The plasma creatinine increases

slowly initially

GFR and plasma creatinine

1. A high serum creatinine suggests a low GFR

2. A normal serum creatinine is not proof of normal GFR

Serum creatinine is also dependent on a persons muscle mass

A high serum creatinine suggests a low GFR because there are no other significant factors that change the serum creatinine

Renal Clearance

• Clearance is a concept – not a real value• It refers to plasma - unit : ml/min• It can be determined for any substance excreted

in the urine• Parameters needed for calculation are plasma

concentration, urine concentration and urine flow rate

• The clearance of certain substances are determined as indicators of renal function

• Blood levels of some substances excreted in urine are sometimes used as indicators of glomerular function

• But blood levels do not change proportionately with changes in GFR