Tutorial: GFR and Renal Clearance

Question 1

What are the normal values for GFR in young adults?

Answer 1

120 mL/min per 1.73 m2

Question 2

What is the fairly typical value for the body surface area of an adult?

Answer 2

1.73m2

Question 3

What is the normal range for GFR in young adults?

Answer 3

90-150 mL/min per 1.73 m2

Question 4

What happens to the value of GFR after the age of 40?

Answer 4

GFR falls by about 10 mL/min per decade.

Question 5

Define Glomerular Filtration Rate (GFR).

Answer 5

sum of filtration of all functioning nephrons (= net ultrafiltration pressure x ultrafiltration coefficient)

Question 6

Define freely filtered substance.

Answer 6

substance which is completely filtered by the juxtaglomerular apparatus, and neither secreted or reabsorbed

present in the plasma, small enough to be freely filtered into Bowman’s capsules, but neither reabsorbed from nor secreted into the tubules

its concentration in the glomerular filtrate is the same as in plasma

Question 7

Is direct measurement of GFR possible?

Answer 7

no it is impossible, but an indirect determination can be made using a marker substance with certain properties.

Question 8

What is the formula relating GFR to urine flow rate?

Answer 8

GFR x Plasma conc. of Y (PY) = urine flow rate (V) x Urine conc. of Y (UY)

GFR = (V x UY) / PY

[P subscript Y)

Question 9

What substance can be used as an indirect marker for GFR?

Answer 9

Inulin

Question 10

What is inulin?

Answer 10

a polysaccharide with a molecular weight of approximately 5000 Daltons.

Question 11

Why do we measure GFR?

Answer 11

most important single means of assessing renal function

Most renal diseases result in a progressive destruction of functioning nephrons.

GFR can be used to document the presence, estimate the severity, and follow the course of kidney disease.

GFR is useful in determining the correct dosage of certain drugs. Many drugs, notably digoxin (used in the treatment of heart conditions) and certain antibiotics, are excreted from the body primarily by glomerular filtration in the kidneys. (if GFR is reduced, the excretion of the drug will fall and it will accumulate in the body, possibly to toxic levels)

Question 12

List 5 properties of inulin which makes it an ideal marker for GFR calculation.

Answer 12

Freely filtered by the glomerulus

not synthesised or metabolised by the kidney

not toxic

measurable in urine and plasma

is not secreted or reabsorbed in the tubules

Question 13

What is the definition of renal clearance?

Answer 13

The renal clearance of a substance is equal to the volume of plasma which would be required to supply that amount of the substance excreted by the kidneys per unit time.

clearance will always be expressed as a volume of plasma per unit time.

Question 14

What is the equation for renal clearance?

Answer 14

For any substance Z, the renal clearance, CZ, is calculated as CZ = (V x UZ) /PZ

PZ and UZ are the concentrations of Z in plasma and urine, respectively and V is the urine flow rate.

(C subscript Z)

Question 15

When will clearance equal GFR?

Answer 15

if the substance is freely filtered and neither reabsorbed nor secreted

Question 16

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

Answer 16

substance X is being secreted into the glomerular filtrate

Question 17

What conclusion can you draw about a sodium clearance that is lower than that of inulin?

Answer 17

sodium is more greatly reabsorbed

Question 18

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 18

No, it could be filtered at very low levels, and then secreted by still at very low levels. Or it could be filtered and secreted, and then partially reabsorbed.

Question 19

Where is para-amino hippuric acid (PAH) secreted into?

Answer 19

it is is secreted avidly into the proximal tubule

Question 20

What ensures that the PAH arriving at the kidneys in the plasma appears in the urine?

Answer 20

Provided the plasma concentration isn’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 in the renal vein.

(NB: PAH does not occur naturally in the body; it has to be infused.)

Question 21

What is PAH used to give an estimate for?

Answer 21

volume of plasma perfusing the kidneys per unit time (renal plasma flow rate (RPF)).

Question 22

Give the equation for the rate at which PAH enters the kidneys per minute in the renal arteries.

Answer 22

RPF X PPAH

Question 23

Give the equation for the rate of excretion of PAH in the urine.

Answer 23

UPAH x V

Question 24

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

Answer 24

Everything that enters the kidney is excreted in the urine

(RPF = (V x UPAH)/PPAH)

PAH is not synthesised in the body, does not alter renal plasma flow and as PAH is completely removed from blood that passes through the kidneys (PAH undergoes both glomerular filtration and tubular secretion) and therefore the rat at which the kidneys can clear PAH from the blood reflects total renal plasma flow.

Question 25

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

Answer 25

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

inulin clearance = GFR = 125ml/min = rate of plasma filtered

proportion filtered = 125/625 = 20%

Question 26

If, in the same person, the arterial plasma inulin concentration were 1 mmol/L, what would be the plasma inulin concentration in:

a) the efferent arteriole.
b) the renal vein.

Answer 26

a) 0.8 mmol/L

b) 0.8 mmol/L

Question 27

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

Answer 27

PAH clearance is not a reliable diagnostic tool (active process which is reliant on the kidneys)

Question 28

What are the 3 main methods of estimating GFR?

Answer 28

Inulin clearance

creatinine clearance (Ccreatinine)

51 CrEDTA clearance

Question 29

How does inulin clearance work to estimate GFR?

Answer 29

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 30

How does Creatinine clearance work to estimate GFR?

Answer 30

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.

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 31

What is needed for measurement of Ccreatinine?

Answer 31

24hr urine collection

a single plasma sample taken at some time during the clearance period

Question 32

Why is inulin not given orally when measuring inulin clearance?

Answer 32

cannot digest it as it is a plant polysaccharide, hence oral inulin cannot enter the plasma

Question 33

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

Answer 33

inulin is given through IV and hence measurement period is short - hence needs to collect sample straightaway

more samples are taken over a longer period of time (inaccuracies are decreased)

Question 34

Ms Rose, 30-years old, normal built, is being investigated for possibility of renal disease, the following data was obtained:

24 hours urine volume = 2L; Urine creatinine concentration = 8 mmol/L; Plasma creatinine concentration = 0.4 mmol/L.

a) Calculate her GFR
b) Is her GFR normal?

Answer 34

a) GFR = CCreatinine = (V x UCreatinine ) / PCreatinine

= (2x 8)/0.4 = 40L/Day

= 27.78ml/min

b) no

Question 35

How does 51 CrEDTA clearance work to estimate GFR?

Answer 35

The substance usually used is EDTA, which can be conveniently labelled with 51CrEDTA, a gamma-emitter. 51CrEDTA clearance can be determined by administering the substance as a single injection, and then measuring the plasma activity of 51Cr at subsequent intervals.

(See log graph for 11.2 BRS Task 7)

The clearance of 51Cr EDTA can be calculated from the slope of the straight line (The greater the slope the greater the clearance).

Question 36

Which one between Cinulin and Ccreatinine is more accurate?

Answer 36

in the measurement of GFR, Cinulin is accurate but inconvenient, whilst Ccreatinine 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 37

What is the advantage of using 51 CrEDTA clearance to estimate GFR?

Answer 37

The advantage of this method is that in practice it requires only -

injection of a single dose of 51Cr EDTA.

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, for the purpose of illustration on the graphs above).

Question 38

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 38

sudden drop as it diffuses down the concentration gradient into a larger space

Question 39

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

Answer 39

shallower gradient (therefore less steep gradient)