Session 3: Measurement of Kidney Function - GFR and Creatinine Clearance

Question 1

Normal GFR range.

Answer 1

Around 90-120 ml/min

Question 2

What does GFR depend on?

Answer 2

Age Gender Size of individual Size of kidneys Pregnancy Ethnicity

Question 3

How does age affect GFR?

Answer 3

Babies only have their nephron development finished by 35th to 36th week of foetal development. At birth GFR is around 20 ml/min but normal GFR will be reached around 18 months. In elderly people the GFR starts to decline already after 30 years of age. The rate of decline is around 6-7 ml/min per decade and there will be loss of functioning nephrons. However there is some compensatory hypertrophy of the kidneys to make up for this.

Question 4

How does pregnancy affect GFR?

Answer 4

GFR increases about 50% in pregnancy. The kidney size increases about 1 cm and there is an increase in fluid volume both vascular and interstitial.

Question 5

Can we measure GFR?

Answer 5

No there is no way to measure actual GFR?

Question 6

So how is it measured instead?

Answer 6

Through something called clearance or rather renal clearance.

Question 7

Define clearance.

Answer 7

The volume of plasma cleared of a substance per unit of time where the substance is denoted as x. Cx = (Ax)/(Px) C = Clearance ml/min A = amount of substance eliminated per unit time (mg/min) P = plasma concentration of substance (mg/ml) This is clearance of the body and not limited to the kidneys.

Question 8

Explain clearance.

Answer 8

If there is a concentration of 5 mg/ml of substance in the plasma and after a minute there is only 3 mg/ml left. This means that 2 mg of substance was eliminated in one minute aka 2mg/min. To put this into equation this gives us 2/5 = 0.4. 0.4 ml/min is the clearance.

Question 9

Define renal clearance.

Answer 9

Excretion rate = U (amount in urine) x V (urine flow rate) Cx = (Ux X V) / Pax Cx is renal clearance Ux amount in urine mg/ml V = urine flow rate ml/min Pax = arterial plasma concentration (mg/ml)

Question 10

Explain renal clearance.

Answer 10

The concentration of a substance in urine multiplied with the urine flow rate gives us an excretion rate of that substance. This excretion rate is contrasted to the arterial plasma concentration of that same substance.

Question 11

A substance is present in urine at a conc of 100 mg/ml Urine flow rate is 2 ml/min The arterial plasma concentration is 4 mg/ml. What is the renal clearance?

Answer 11

100 x 2 = 200 200/4 = 50 Renal clearance = 50 ml/min

Question 12

A substance is present in urine at a conc of 100 mg/ml Urine flow rate is 10 ml/min. Arterial plasma conc is still 4 mg/ml. What is the renal clearance?

Answer 12

100 x 10 = 1000 1000 /4 = 250 Renal clearance = 250 ml/min

Question 13

Give criteria of a substance used to measure GFR.

Answer 13

Be produced at a constant rate Be freely filtered across the glomerulus Not be reabsorbed in the nephron Not be secreted into the nephron

Question 14

Give examples of substances used to measure GFR.

Answer 14

Inulin 51 Cr-EDTA Iohexol Creatinine

Question 15

What is inulin and how is it used to measure GFR?

Answer 15

Inulin is an exogenous polysaccharide which is essentially a dietary fibre. This means that it is not produced at a constant rate however it is freely filtered, not reabsorbed and not secreted. Therefore inducing this at a constant rate and then measuring it would give us a very accurate measurement of GFR.

Question 16

Is inulin used to measure GFR?

Answer 16

No, it is impractical and not used clinically.

Question 17

Why is inulin not used?

Answer 17

Because it requires continuous IV administration to maintain a steady state. Also it requires a catheter and timed urine collection in order to give a good measurement of GFR.

Question 18

What is 51 Cr-EDTA and how is it used to measure GFR?

Answer 18

It is a radio-active labelled marker that is cleared exclusively through renal filtration.

Question 19

Is 51 Cr-EDTA used to measure GFR?

Answer 19

Yes in some cases.

Question 20

In which cases is 51Cr-EDTA used?

Answer 20

In children When there is indication of renal function required like for cancer medication. Assessment of kidney function for someone who is going to donate a kidney.

Question 21

Why is 51 Cr-EDTA not readily used? Why is it superior to inulin?

Answer 21

Because it is still impractical. It does only need a one time administration and not continuous. However it has a 10% lower clearance than inulin.

Question 22

Why is creatinine a measure of GFR?

Answer 22

It is an endogenous substance which is more or less produced at a constant rate. It is freely filtered and not reabsorbed. However it is secreted into the nephron.

Question 23

How can creatinine clearance be measured?

Answer 23

By urine creatinine over 24 hours or by serum creatinine.

Question 24

Disadvantages of creatinine measuring.

Answer 24

It can be inconvenient as you have to carry a bottle of urine. Frequently inaccurate Overestimates GFR by 10-20% due to creatinine secretion. There are factors which affect creatinine levels.

Question 25

Serum creatinine measurement in UK vs USA.

Answer 25

132 micromol/L in UK 1.5 mg/dl in US Conversion is to divide UK by 88.4

Question 26

Normal serum creatinine.

Answer 26

70-150 micromol/L

Question 27

Give examples of factors that affect creatinine levels in an individual.

Answer 27

Muscle mass Intake of meat Age Creatine supplements Vegetarian Ethnicity

Question 28

Relationship between true GFR and serum Creatinine

Answer 28

An inverse relationship that is not linear.

Serum creatinine is lower than expected because there is secretion of Cr into the tubules.

Question 29

What is eGFR?

Answer 29

Estimated GFR derived from serum creatinine. Since creatinine is not true GFR we don’t blindly translate serum creatinine to GFR and instead we give an estimate.

Question 30

There are different eGFRs.

Give examples

Answer 30

MDRD eGFR

CKD-EPI

Question 31

Explain MDRD-eGFR

Answer 31

It is a 4 variable equation which takes

Serum creatinine

Age

Sex

Caucasian or black

into account.

It is standardised to body surface area of 1.73 m2 so height and weight is not needed.

Question 32

When is MDRD eGFR inaccurate?

Answer 32

Peple without kidney disease

Children

Pregnancy

Old age

Other ethnicities than caucasian or black

Amputees

Patients with higher levels of kidney function (>60 ml/min)

Question 33

Explain CKD-EPI.

Answer 33

Slightly different calculation but still 4 basic variables:

Serum creatinine

Age

Sex

Black/Caucasian

Question 34

Advantages of CKD-EPI.

Answer 34

As accurate as MDRD when eGFR is less than 60ml/min

More accurate over 60ml/min

Question 35

Why is eGFR less accurate with mild kidney disease?

Answer 35

Reduction in GFR causes increase in blood flow

Reduced nephron number leads to nephron hypertrophy so no change in GFR

Reduced filtration of creatinine due to reduced GFr results in an increased serum creatinine and increased secretion into the tubule to maintain steady state of serum creatinine.