GFR and Renal Clearance

Question 1

What is GFR?

Answer 1

It is the amount of fluid filtered from the glomeruli into the Bowman’s capsule per unit time (mL/min). Sum of filtration rate of all functioning nephrons.

Question 2

What is freely filtered substance?

Answer 2

For substance X,

ConcentrationX (Plasma) = ConcentrationX (Glomerular filtrate)

Question 3

How do you calculate GFR?

Answer 3

Question 4

What are properties of inulin which make it an ideal marker for GFR calculation?

Answer 4

Freely filtered
No reabsorption
No secretion
Non-toxic
Can be measured in plasma & urine

Question 5

What conclusion can you draw about a substance whose renal clearance is higher than that of inulin?

Answer 5

Secretion of that substance occurs

Question 6

If the renal clearance of a substance X is lower than that of inulin, does this rule out the possibility of X being secreted into the tubular fluid?

Answer 6

No, it could be secreted, but possibly more is being reabsorbed.

Question 7

Answer 7

Question 8

Explain the reasoning behind clearance of PAH being able to give an estimate of the rate of renal plasma flow.

Answer 8

Question 9

If PAH clearance = 625 ml/min and the inulin clearance = 125ml/min, what proportion of the plasma entering the glomeruli is filtered?

Answer 9

PAH clearance = RPF = 625 ml/min = rate of plasma entering kidney

Inulin clearance = GFR = 125ml/min = rate plasma filtered

Proportion filtered = 125/625 = 20% (the filtration fraction)

Question 10

Why is measurement of PAH clearance rarely performed clinically when renal disease is suspected?

Answer 10

Abnormal PAH clearance could be due to:
- Issues with renal plasma flow
- Incomplete secretion

Therefore, reliability of test is affected.

Question 11

What are the 3 main methods of estimating GFR clearance?

Answer 11

(a) Inulin Clearance.

(b) Creatinine clearance (C creatinine)

1. 24h urine collection
2. a single plasma sample taken at some time during the clearance period

Creatinine shares most of the properties of inulin. It is freely filtered and neither reabsorbed nor metabolised by the kidneys. However, since a small amount of creatinine enters the urine by secretion into the proximal tubule, the amount excreted slightly exceeds the amount filtered. In addition, the method used to measure creatinine concentrations is not sufficiently specific: in addition to creatinine it measures the concentrations of so-called “non-creatinine chromogens” present in plasma but not usually in urine. However, these two errors tend to cancel out and because of its simplicity Ccreatinine is widely used as an estimate of GFR.

Question 12

What are the issues with inulin clinically?

Answer 12

Inulin does not occur naturally in the body, so, in order to measure its renal clearance, it has to be infused intravenously.

The requirement for intravenous infusion causes several problems, which mean that measurement of inulin clearance is rarely used clinically.

In particular, it is time consuming and tedious, requires several blood samples, and, because of the short duration over which measurements are usually made, bladder catheterisation (since voluntary bladder emptying may be incomplete).

Question 13

Why is creatinine advantageous over inulin?

Answer 13

Creatinine has a major advantage over inulin in that it is an endogenous substance, produced from the metabolism of muscle creatine.

Moreover, it is released into the blood at a relatively constant rate, so the plasma concentration of creatinine remains fairly stable in a given individual.

Question 14

What are similarities between inulin and C creatinine?

Answer 14

It is freely filtered and neither reabsorbed nor metabolised by the kidneys.

Question 15

What are the issues with creatinine?

Answer 15

However, since a small amount of creatinine enters the urine by secretion into the proximal tubule, the amount excreted slightly exceeds the amount filtered.

In addition, the method used to measure creatinine concentrations is not sufficiently specific: in addition to creatinine it measures the concentrations of so-called “non-creatinine chromogens” present in plasma but not usually in urine.

However, these two errors tend to cancel out and because of its simplicity C creatinine is widely used as an estimate of GFR.

Question 16

What is the normal value for GFR?

Answer 16

90-150 mL/min

Question 17

When does GFR start to fall, and by how much?

Answer 17

at the age of 40 and it falls by about 10 mL/min per decade

Question 18

What is inulin?

Answer 18

a polysaccharide with a molecular weight of approximately 5000 daltons

Question 19

How is PAH secreted?

Answer 19

para aminohippuric acid is secreted avidly into the proximal tubules
- provided the plasma concentrations aren’t too high, the combination of filtration and secretion ensures that practically all the PAH arriving at the kidneys in the plasma appears in the urine (and virtually none leaves the renal vein)

Question 20

Why is inulin not given orally when measuring inulin clearance?

Answer 20

insulin is a starchy substance, bacteria of gut can use it as its own food so less is left as it is metabolised

Question 21

Why is bladder catheterisation not usually considered necessary when creatinine clearance is measured although it is required for measurement of inulin clearance?

Answer 21

Inulin is added externally and has a particular time frame in body and will be eventually removed from the body, but creatinine is always in the body.

Question 22

What can be used intsead of inulin and creatinine?

Answer 22

EDTA/ 51Cr EDTA (a gamma emitter)

Question 23

Why is EDTA preferred?

Answer 23

From the foregoing we can say that in the measurement of GFR, C inulin is accurate but inconvenient, whilst C creatinine is convenient but not so accurate.

Because of these problems, many clinical laboratories now use substances with the same properties as inulin, but which can be measured more easily, by virtue of the fact that they emit radiation.
This allows them to be readily and accurately quantified in plasma.
The clearance of such substances can be determined by monitoring their disappearance from the plasma after administering a given dose, thus eliminating the need to collect urine.

Question 24

How would EDTA be administered and how would it be measured?

Answer 24

one injection, then measure plasma activity of 51Cr at subsequent intervals

Question 25

How is the slope of a EDTA log graph linked to clearance?

Answer 25

The greater the slope the greater the clearance

Question 26

What is the advantage of EDTA?

Answer 26

1) injection of a single dose of 51Cr EDTA.

2) collection of 2-3 plasma samples taken at appropriate times after the injection (i.e. on the straight line portion of the curve; far fewer samples are necessary than are shown).

Question 27

Given the fact that 51Cr EDTA is free to permeate the whole of the extracellular fluid, how do you explain the initial steep phase of the plasma disappearance curve (log plasma 51Cr EDTA vs Time) following a single IV injection of 51Cr EDTA.

Answer 27

Because it quickly diffuses (quick diffusion rate) initially in the extracellular fluid down concentration gradient

At that point it is removed from the plasma at a consistent rate

Question 28

How would the plasma disappearance curve (log plasma 51Cr EDTA vs Time) be affected in someone suffering from severe renal failure?

Answer 28

less steep line, gradient because of slower clearance

renal failure is a lower glomerular filtration rate